ES2378669T3 - HIV protease inhibitor compounds - Google Patents

Abstract

A compound, stereoisomer of the compound, ester of the compound, a pharmaceutically acceptable salt of the compound, a stereoisomer, or an ester, or a combination thereof in which: the compound corresponds in structure to formula (II): X is O ; R1 is alkyl; R2 is selected from the group consisting of cycloalkylalkyl, cycloalkenylalkyl, arylalkyl, heterocycloalkyl and heteroarylalkyl; R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkylalkyl, cycloalkenylalkyl, heterocycloalkyl, heteroarylalkyl, arylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkyl, alkyl, alkyl - alkylSORa, -alkylSO2Ra, -alkylNRaRb, -alkyl C (= O) ORa, -alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) Ra, - alkylN (Rb) SO2Ra and -alkyl (Rb) SO2NRaRb, in which: the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkenyl alkyl, cycloalkenyl radical of the heterocycloalkyl radical, heteroaryl heteroaryl radical, and aryl radical are substituted by the aryl radical. , 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -SH, -S (alkyl), -S (haloalkyl), -SO2 (I rent ), -SO2 (haloalkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl , -C (= O) OH, -C (= O) O (alkyl), - C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N ( alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkyl SH, -alkyl (alkyl), -alkSO2 (alkyl), -alkyl NH2, - alkylN (H) (alkyl) , -alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, - alkylC (= O) OH, -alkylC (= O) O (alkyl) , -C-alkyl (= O) NH2, -C-alkyl (= O) N (H) (alkyl), - alkylC (= O) N (alkyl) 2, - alkylC (= O) alkyl and R3a; R3a is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy and heterocyclooxy, in which each substituent is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo , nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, -SH, -S (alkyl), - SO2 (alkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2 , -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, - C (= O) O (alkyl), -C (= O) NH2, -C (= O) N (H) (alkyl), -C (O) N (alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS (alkyl), -alkylSO2 (alkyl), -alkylNH2, -alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C ( = O) alkyl, -alkyl C (= O) OH, - alkylC (= O) O (alkyl), -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl), -alkylC (= O) N (alkyl) 2 and -C1 alkyl (= O) alkyl; R4 is selected from the group consisting of: a) -C (O) CH (R8) NHC (O) R9, b) -C (O) R9, c) -C (O) CH2-O-aryl, substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl , -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2, d) -C (O) CH2-O-heteroaryl, substituted with 0, 1, 2 or 3 substituents selected independently from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl , -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and - C (= O) N (alkyl) 2 , R5 is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle, in which: each substituent is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl , cyano, halo, nitro, oxo, -ORa, -OC (= O) Ra, -SRa, -SORa, - SO2Ra, -SO2NRa, -SO2OR3, -NRaRb, -N (Rb) NRaRb, -10 N (Rb ) C (= O) Ra, -N (Rb) SO2Ra, -N (Rb) C (= O) ORa, - N (Rb) C (= O) NRaRb, -N (Rb) SO2NRaRb, -C (= O) Ra, -C (= O) NRaRb, -C (= O) ORa, azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylORa, -alkylOC (= O) Ra, -alkylSRa, -alkylSORa, -alkSO2Ra, -alkylSO2NRa , - alkylSO2ORa, -alkylNRaRb, -C (H) = N (ORa), -C (alkyl) = N (ORa), -C (H) = NNR3Rb, -C (alkyl) = NNRaRb, - C (H) (= NORa) NRaRb, -C (alkyl) (= NORa) NRaRb, -alkylN (Rb) NRaRb, -alkylN (Rb) C (= O) Ra, - alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) NRaRb, -alkylN (Rb) SO2NR3Rb, -alkylN (Rb) SO2Ra, -alkyl C (= O) Ra, - alkylC (= O) ORa, -alkyl C (= O) NRaRb and R5a; R5a is selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, in which: each substituent is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (H) (alkyl), - N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -N (H) C (= O) NH2, - N (H) C (= O) N (H) (alkyl ), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N ( H) (alkyl), -C (= O) N (alkyl) 2, cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2, - alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN ( H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, - alkylN (H) C (= O) NH2; -alkyl N (H) C (= O) N (H) (alkyl), -alkyl (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, - alkylC (= O) Oalkyl, -C1 alkyl (= O) NH2, -Calkyl (= O) N (H) (alkyl) and -C1 alkyl (= O) N (alkyl) 2; R8 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl and arylalkyl, in which: each of said substituents is substituted with 0, 1 or 2 substituents independently selected from the group consisting in halo, cyano, formyl, nitro, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (R) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, - C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C (= O) alkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2, - alkylN (H) alkyl, -alkylN (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -alkylC (= O) NH2, - alkylC ( = O) N (H) (alkyl) and -C1 alkyl (= O) N (alkyl) 2; R9 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heterocycle, heteroaryl and OR9a, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting in hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, - C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2; R9a is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl and heterocycloalkyl, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, - C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2; R10 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl and heteroarylalkyl, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents selected independently from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, -SRa, -SORa, -SO2R3, -SO2NRaRb, -C (= O) Ra, -NRaRb, -N (Rb ) C (= O) Ra, -N (Rb) C (= O) ORa, -N (Rb) SO2Ra, - N (Rb) SO2NRaRb, -N (Rb) C (= NH) NRaRb, -N (Rb ) C (= O) NRaRb, -C (= O) NRaRb and -C (= O) ORa; R11 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R12 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R13 is selected from the group consisting of alkyl and haloalkyl; R14 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl and heterocycle, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo , cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, haloalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and - C (= O) N (alkyl) 2; Z is selected from the group consisting of -CH2-, -NH-, -O- and -S-; Z 'is selected from the group consisting of -CH2-, -NH-, -O- and -S-; Ra and Rb in each case are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, arylalkyl and heteroarylalkyl, in which: each of said substituents is substituted with 0 , 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, -NH2, -N (H) (alkyl), -N ( alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, - N (alkyl) C (= O) alkyl, -N (H) C ( = O) NH2, -N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, - C ( = O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C (= O) alkyl, cyanoalkyl, formylalkyl , nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2, -alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) NH2, -alkylN (H)

Description

HIV protease inhibitor compounds

5 Technical field

This refers to new compounds and a composition and method for inhibiting the protease of the human immunodeficiency virus (HIV), a composition and method for inhibiting or treating an HIV infection, processes for preparing the synthetic compounds and intermediates employed in the processes.

Background of the invention

The human immunodeficiency virus (HIV) genome encodes a protease that is responsible for the proteolytic processing of one or more polyprotein precursors such as pol and gag gene products.

15 HIV protease processes the precursor of gag to major proteins and also processes the precursor of pol to reverse transcriptase and protease.

Proper processing of precursor polyproteins by HIV proteases is necessary for the assembly of infectious virions. Therefore, HIV protease inhibition provides a useful target for the development of

20 therapeutic agents for the treatment of HIV infection.

In recent years, HIV protease inhibitors have become an important class of therapeutic agents for inhibition and treatment of HIV infections in humans. HIV protease inhibitors are especially effective when administered in combination with other classes of therapeutic agents of

25 HIV, especially HIV reverse transcriptase inhibitors, in "cocktails" of HIV therapeutic agents.

Currently, HIV protease inhibitors saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir / ritonavir, fosamprenavir and atazanavir have been approved in the United States for treatment of HIV infection. There is a continuing need for improved HIV protease inhibitors that are very potent, which

30 have reduced side effects and are effective against resistant strains of HIV.

WO 97/19055 analyzes azahexane derivatives suitable for inhibiting retroviral aspartate proteases. WO 98/034476 analyzes anilinopeptide derivatives suitable for inhibiting HIV protease.

35 Summary of the invention

The present invention provides a compound, a stereoisomer of the compound, an ester of the compound, a pharmaceutically acceptable salt of the compound, a stereoisomer, or an ester, or a combination thereof.

40 in which:

The compound corresponds in structure to formula (II):

X is 0;

R1 is alkyl R2 is selected from the group consisting of cycloalkylalkyl, cycloalkenylalkyl, arylalkyl, heterocycloalkyl and heteroarylalkyl; R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkylalkyl, cycloalkenylalkyl,

50 heterocycloalkyl, heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSRa, -alkylSORa, -alkylSO2Ra, alkylNRaRb, -alkyl C (= O) ORa, -alkylN (Rb) C (= O) ORa, -alkN (Rb = (C) O) Ra, -alkyl (Rb) SO2Ra and -alkylN (Rb) SO2NRaRb, in which:

the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl, cycloalkenyl moiety

55 of the cycloalkenyl alkyl radical, heterocycle of the heterocycloalkyl radical, heteroarylalkyl heteroaryl, and the aryl radical of the arylalkyl are substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl , alkynyl, hydroxy, alkoxy, -SH, -S (alkyl), -S (haloalkyl), SO2 (alkyl), -SO2 (haloalkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, -C (= O) O (alkyl), -C (= O ) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, - alkylSH, -alkylS (alkyl), -alkylSO2 (alkyl), alkylNH2, -alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylC (= O) OH, -alkylC (= O) O (alkyl), -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl), -alkylC ( = O) N (alkyl) 2, -C1 alkyl (= O) alkyl and R3a;

R3a is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy and heterocyclooxy, in which

each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, -SH, -S (alkyl) ,

10 -SO2 (alkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, -C (O) O (alkyl), -C (-O) NH2, -C (-O) N (H) (alkyl), -C (O) N (alkyl) 2 , -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkyl SH, -alkyl S (alkyl), -alkSO2 (alkyl), -alkyl NH2, alkylN (H) (alkyl), -alkylN ( alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylC (= O) OH, alkylC (= O) O (alkyl), -alkylC (= O) NH2, -C1 (= O) N (H) (alkyl), -C (= O) N (alkyl) 2 and -C (= O) alkyl;

15 R4 is selected from the group consisting of:

a) -C (O) CH (R8) NHC (O) R9, b) -C (O) R9, c) -C (O) CH2-O-aryl, substituted with 0.1, 2 or 3 substituents independently selected from the group

20 consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2, d) -C (O) CH2-O-heteroaryl, substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl,

Alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2, e)

30 f)

g)

h) i)

j)

5k)

Y I) -SO2R14;

R5 is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle, in which:

each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, -ORa, -OC (= O) Ra, - SRa, -SORa, -SO2Ra, -SO2NR3, -SO2OR3, -NR3Rb, -N (Rb) NR3Rb, -N (Rb) C (= O) R3, -N (Rb) SO2R3, -N (R3) C ( -O) OR3,

15 N (Rb) C (= O) NR3, Rb, -N (Rb) SO2NRaRb, -C (= O) Ra, -C (= O) NRaRb, -C (= O) ORa, azidoalkyl, haloalkyl, nitroalkyl , cyanoalkyl, -alkylORa, -alkylOC (= O) Ra, -alkylSR3, -alkylSOR3, -alkylSO2R3, -alkylSO2NR3, -alkylSO2OR3, alkylNR3Rb, -C (H) = N (OR3), -C (alkyl) = N ( OR3), -C (H) = NNR3Rb, -C (alkyl) = NNR3Rb, -C (H) (= NOR3) NR3Rb, C (alkyl) (= NOR3) NR3Rb, -alkyl N (Rb) NRaRb, -alkylN ( Rb) C (= O) Ra, -alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) NRaRb, alkylN (Rb) SO2NR3Rb, -alkylN (Rb) SO2R3, -alkylC (= O) R3, -alkylC (= O) OR3, -alkylC (= O) NRaRb and R5a;

R5a is selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, in which:

each of said substituents is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N ( H) (alkyl), 25 -N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O ) alkyl, -N (H) C (= O) NH2, N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), C (= O) N (alkyl) 2, cyanoalkyl, formylalkyl , haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH2, -alkylN (H) (alkyl), alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, - alkylN (H) C (= O) NH2, alkylN (H) C (= O) N (H) (alkyl), -alkylN (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -alkylC (= O) NH2,

C 1 -C (= O) N (H) (alkyl) and -C (-O) N (alkyl) 2;

R8 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl and arylalkyl, in which:

Each of said substituents is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, cyano, formyl, nitro, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (H) alkyl , N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) ( alkyl), -C (= O) N (alkyl) 2, C (= O) alkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2,. -alkylN (H) alkyl, -alkylN (alkyl) 2, -alkylC (= O) OH, alkylC (= O) Oalkyl, -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl) and -alkylC (= O) N (alkyl) 2;

R9 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heterocycle, heteroaryl and OR9a, in which:

each of said substituents is substituted with 0, 1, 2 or 3 independently selected substituents

5 among the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, - C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2;

R9a is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl and heterocycloalkyl, in which:

each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, N (H) alkyl , -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and

15 C (= C) N (alkyl) 2;

R10 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl and heteroarylalkyl, wherein:

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, -SRa, -SORa, -SO2R3, -SO2NRaRb, -C (= O) Ra, -NRaRb, -N (Rb) C (= O) R11, -N (Rb) C (= O) ORa, -N (Rb) SO2Ra, -N (Rb) SO2NRaRb, N (Rb) C (= NH) NRaRb, -N (Rb) C (= O) NRaRb, -C (= O) NRaRb and -C (= O) ORa;

R11 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R12 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R13 is selected from the group consisting of alkyl and haloalkyl; R14 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl and heterocycle, in which:

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, haloalkyl, -NH2, N (H) alkyl, -N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C ( = O) N (alkyl) 2;

Z is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Z 'is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Ra and Rb in each case are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, alkynyl; cycloalkyl, aryl, heteroaryl, heterocycle, arylalkyl and heteroarylalkyl, in which:

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, -NH2, N ( H) (alkyl), -N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -N (H) C (= O) NH2, -N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), C (= O) N (alkyl) 2, -C ( = O) alkyl, cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl,

Alkyl NH2, -alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) NH2, -alkylN (H) C (= O) N (H) (alkyl), alkylN (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -alkylC (= O) NH2, -alkyl C (= O) N (H) (alkyl ), C (= O) N (alkyl) 2 alkyl and -C (= O) alkyl; and n is 1.

The present invention also provides a pharmaceutical composition comprising an amount.

Therapeutically effective of a compound or combination of compounds of the present invention, or a pharmaceutically acceptable salt form, a stereoisomer, ester, salt of an ester, or a combination thereof, and a pharmaceutically acceptable carrier.

The present invention further provides a pharmaceutical composition comprising an amount.

Therapeutically effective of a compound or combination of compounds of the present invention, or a pharmaceutically acceptable salt, steroisomer, ester, salt form, or combination thereof, and one, two, three, four, five or six agents selected from the group consisting of a second HIV protease inhibitor, an HIV reverse transcriptase inhibitor, an HIV entry / fusion inhibitor, an HIV integrase inhibitor and an HIV germination / modulation inhibitor and a vehicle pharmaceutically acceptable.

The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of the present invention, or a pharmaceutically acceptable salt, stereoisomer, ester, salt form, or combination thereof, or combination thereof. ritonavir and a pharmaceutically acceptable carrier.

The present invention further provides the use of one or more compounds, stereoisomers, esters and / or salts of the present invention to prepare a medicament for inhibiting the replication of an HIV virus by contacting said virus with a therapeutically effective amount of a compound or combination of compounds of the present invention, or a form of salt, stereoisomer, ester, salt of an ester or combination thereof

5 pharmaceutically acceptable.

The present invention further provides use of a pharmaceutical composition of the present invention to prepare a medicament for inhibiting the replication of an HIV virus by contacting said virus with the pharmaceutical composition of the present invention.

The present invention further provides the use of one or more compounds, stereoisomers, esters and / or salts of the present invention to prepare a medicament for inhibiting an HIV protease by contacting said HIV protease with a therapeutically effective amount of a compound. or combination of compounds of the present invention, or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof,

15 pharmaceutically acceptable.

The present invention further provides the use of a pharmaceutical composition of the present invention to prepare a medicament for inhibiting an HIV protease by contacting said HIV protease with the pharmaceutical composition of the present invention.

The present invention also provides the use of one or more compounds, stereoisomers, esters and / or salts of the present invention to prepare a medicament for treating or preventing an HIV infection by administering to a patient in need of such treatment a therapeutically effective amount of a compound or combination of compounds of the present invention or a form of salt, stereoisomer, ester, salt of an ester, or combination of the

25 same, pharmaceutically acceptable.

The present invention also provides use of a pharmaceutical composition of the present invention to prepare a medicament for treating or preventing an HIV infection by administering to a patient in need of such treatment the pharmaceutical composition of the present invention.

Detailed description of the invention

As used herein, the following terms have the indicated meanings:

35 As used herein, the singular forms "a", "a" and "the" may include plural references, unless the context clearly indicates otherwise.

The term "activated carboxylic acid group", as used herein, refers to acid halides, such as acid chlorides and also refers to activated ester derivatives that include, but are not limited to,

40 anhydrides derived from formic acid and acetic acid, anhydrides obtained from alkoxycarbonyl halides, such as isobutyloxycarbonyl chloride and the like, anhydrides obtained from the reaction of carboxylic acid with N, N'-carbonyldiimidazole and the like, esters derived from N-hydroxysuccinimide, esters derived from N-hydroxyphthalimide, esters derived from N-hydroxybenzotriazole, esters derived from N-hydroxy-5-norbornene-2,3-medicaboboximide, esters derived from 2,4,5-trichlorophenol, esters derived from p-nitrophenol , esters derived from phenol,

45 esters derived from pentachlorophenol, esters derived from 8-hydroxyquinoline and the like.

The term "alkanoyl," as used herein, refers to an alkyl group, as defined herein, attached to the starting molecular moiety through a carbonyl group. Representative examples of alkanoyl include, but are not limited to, methylcarbonyl, ethylcarbonyl and tert-butylcarbonyl.

The term "alkyl", as used herein, refers to a group obtained from a saturated straight or branched chain hydrocarbon containing 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. Representative examples of alkyl groups include, but are not limited to, butyl, methyl, 1-methylpropyl, 1-methylbutyl, isopropyl (1-methyl ethyl), 2-methylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 3-methylbutyl, 3,3 -dimethylbutyl, tert-butyl and isopropyl (1-methyl ethyl).

The term "alkylamino", as used herein, refers to -N (H) (alkyl).

The term "alkylaminocarbonyl," as used herein, refers to an alkylamino group, as defined herein, attached to the starting molecular moiety through a carbonyl group. An example

Representative alkylaminocarbonyl includes, but is not limited to, acetylamino.

The term "alkenyl", as used herein, refers to a linear or branched chain group of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms containing at least one double carbon-carbon bond. Representative examples of alkenyl groups include, but are not limited to, allyl, propenyl, 3-methyl-2-butenyl and 3,7-dimethyl-6

65 octenyl.

The term "alkynyl", as used herein, refers to a straight or branched chain hydrocarbon of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms containing at least one triple carbon-carbon bond. Representative examples of alkenyl groups include, but are not limited to, ethynyl, 2-methyl-3-butynyl, 3-pentinyl and 2-octinyl.

The term "alkoxy", as used herein, refers to an alkyl group, as defined herein, attached to the starting molecular moiety through an oxygen atom. Representative examples of alkoxy groups include, but are not limited to, tert-butoxy, methoxy and isopropoxy.

The term "alkoxyalkyl," as used herein, refers to an alkyl group substituted with at least one alkoxy group. Representative examples of alkoxyalkyl include, but are not limited to, methoxymethyl and 1-methoxyethyl.

The term "alkoxycarbonyl," as used herein, refers to an alkoxy group attached to the starting molecular moiety through a carbonyl group. Representative examples of alkoxycarbonyl groups include, but are not limited to, tert-butoxycarbonyl, ethoxycarbonyl and methoxycarbonyl.

The term "amino", as used herein, refers to -NH2.

The term "aminoalkyl," as used herein, refers to an amino group attached to the starting molecular moiety through an alkyl group as defined herein.

The term "aryl," as used herein, refers to a phenyl group, or fused bicyclic or tricyclic hydrocarbon ring systems in which one or more of the rings is a phenyl group. Condensed bicyclic ring systems have a phenyl group fused to a monocyclic cycloalkenyl group, as defined herein, a monocyclic cycloalkyl group, as defined herein, another phenyl group. The condensed tricyclic ring systems are illustrated by a condensed bicyclic ring system that is fused to a monocyclic cycloalkenyl group, as defined herein, a monocyclic cycloalkyl group, as defined herein, or another phenyl group. Representative examples of aryl groups include, but are not limited to, anthracenyl, azulenyl, fluorenyl, indanyl, indenyl, naphthyl, phenyl and tetrahydro-naphthyl. The aryl group of the present invention can be connected to the starting molecular moiety through any substitutable carbon atom of the group. The aryl groups of the compounds of the present invention may be substituted.

or without replacing.

The term "arylalkyl," as used herein, refers to an aryl group attached to the starting molecular moiety through an alkyl group. Representative examples of arylalkyl include, but are not limited to,

Phenylmethyl, phenylethyl and naphthylmethyl.

The term "aryloxy", as used herein, refers to an aryl group, as defined herein, attached to the starting molecular moiety through an oxygen atom. Representative examples of aryloxy include, but are not limited to, phenoxy, naphthyloxy, 3-bromophenoxy, 4-chlorophenoxy, 4-methylphenoxy, 3,5-dimethoxyphenoxy, 4-methoxyphenoxy and 4-methylphenoxy.

The term "carbonyl," as used herein, refers to -C (= O).

The term "cyano", as used herein, refers to -CN.

The term "cyanoalkyl," as used herein, refers to a cyano group attached to the starting molecular moiety through an alkyl group.

The term "cycloalkenyl", as used herein, refers to a non-aromatic, partially unsaturated, monocyclic, bicyclic or tricyclic ring system, having three to fourteen carbon atoms and zero heteroatoms. Representative examples of cycloalkenyl groups include, but are not limited to, cyclohexenyl, octahydronaphthalenyl and norbonylenyl. The cycloalkenyl groups of the compounds of the present invention may be substituted or unsubstituted.

The term "cycloalkenyl alkyl", as used herein, refers to a cycloalkenyl group attached to the starting molecular moiety through an alkyl group as defined herein.

The term "cycloalkyl," as used herein, refers to a saturated, monocyclic, bicyclic or tricyclic hydrocarbon ring system having three to fourteen carbon atoms and zero heteroatoms. Representative examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo [3,1,1] heptyl, 6,6-dimethylbicyclo [3,1,1] heptyl and adamantyl. The cycloalkyl groups of the compounds of the present invention may be substituted or unsubstituted.

The term "cycloalkylalkyl," as used herein, refers to a cycloalkyl group attached to the starting molecular moiety through an alkyl group as defined herein.

The term "dialkylamino", as used herein, refers to -NR90R91, wherein R90 and R91 are alkyls.

The term "dialkylaminocarbonyl," as used herein, refers to a dialkylamino group as defined herein, attached to the starting molecular moiety through a carbonyl group. 5 The term "formyl," as used herein, refers to a group -C (O) H.

The term "formylalkyl," as used herein, refers to a formyl group attached to the starting molecular moiety through an alkyl group.

The terms "halo" and "halogen", as used herein, refer to F, Cl, Br and I.

The term "haloalkenyl", as used herein, refers to an alkenyl group, as defined herein, substituted with one, two, three or four halogen atoms.

The term "haloalkoxy", as used herein, refers to a haloalkyl group attached to the starting molecular moiety through an oxygen atom.

The term "haloalkyl," as used herein, refers to an alkyl group substituted with one, two, three or four halogen atoms.

The term "haloalkynyl," as used herein, refers to an alkenyl group, as defined herein, substituted with one, two, three or four halogen atoms.

The term "heteroaryl," as used herein, refers to a five- or six-membered ring in which at least one atom is selected from the groups consisting of N, O and S, and the remaining atoms are carbon. The term "heteroaryl" also includes bicyclic systems in which a heteroaryl ring is fused to a phenyl group, a monocyclic cycloalkyl group, as defined herein, a heterocycle group, as defined herein, or an additional heteroaryl group . The term "heteroaryl" also includes tricyclic systems in which a bicyclic system is fused to a phenyl group, a monocyclic cycloalkyl group, as defined herein, a heterocycle group, as defined herein, or an additional heteroaryl group. . The heteroaryl groups are connected to the starting molecular moiety through any substitutable carbon or nitrogen atom in the groups. Examples of heteroaryl groups include benzothienyl, benzoxazolyl, benzimidazolyl, benzoxadiazolyl, dibenzofuranyl, dihydrobenzothiazolyl, furanyl (furyl), imidazolyl, imidazopyridinyl,

35 indazolyl, indolyl, isoindolyl, isoxazolyl, isoquinolinyl, isothiazolyl, oxadiazolyl, oxazolyl, thiazolyl, thienopyridinyl, thienyl, triazolyl, thiadiazolyl, tetrazolyl, pyridoimidazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, quinolinyl, tetrahydroquinolinyl, tetrahydropyranyl and triazinyl . The heteroaryl groups of the present invention may be substituted or unsubstituted. In addition, nitrogen heteroatoms can optionally quaternize or oxidize to give the N-oxide. In addition, the nitrogen-containing rings may optionally be protected.

The term "heteroaryloxy," as used herein, refers to a heteroaryl group, as defined herein, attached to the starting molecular moiety through an oxygen atom. Representative examples of heteroaryloxy include, but are not limited to, pyridin-3-yloxy and quinolin-3-yloxy.

The term "heteroarylalkyl," as used herein, refers to a heteroaryl group attached to the starting molecular moiety through an alkyl group. Representative examples of heteroarylalkyl groups include, but are not limited to, thiazolylmethyl, thienylmethyl, furylmethyl, imidazolylmethyl and pyridylmethyl.

The term "heterocycle", as used herein, refers to a cyclic, non-aromatic, saturated or partially saturated three, four, five or six-membered ring system containing at least one atom selected from the group consisting of oxygen, nitrogen and sulfur. The term "heterocycle" also includes bicyclic systems, in which a heterocycle ring is fused to a phenyl group, a monocyclic cycloalkenyl group, as defined herein, a monocyclic cycloalkyl group, as defined herein, or a additional monocyclic heterocycle group. The term "heterocycle" also includes tricyclic systems in which a bicyclic system is condensed to a phenyl group, a monocyclic cycloalkenyl group, as defined herein, a monocyclic cycloalkyl group, as defined herein, or a heterocycle group. additional monocyclic. The heterocycle groups of the invention are connected to the starting molecular moiety through any substitutable carbon or nitrogen atom in the group. Representative examples of heterocycle groups include, but are not limited to, benzoxazinyl, dihydroindolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4- benzodioxynil, 2,3-dihydrobenzofuranyl, hexahydrofurofuranyl, iso-indolinyl, morpholinyl, piperazinyl, pyrrolidinyl, tetrahydropyridinyl, piperidinyl, thiomorpholinyl, tetrahydropyranyl. The heterocycle groups of the present invention may be substituted or unsubstituted. In addition, nitrogen heteroatoms can optionally quaternize or oxidize to give the N-oxide. In addition, the

65 heterocyclic rings containing nitrogen may optionally be N-protected.

The term "heterocyclooxy", as used herein, refers to a heterocycle group, as defined herein, attached to the starting molecular moiety through an oxygen atom.

The term "heterocycloalkyl," as used herein, refers to a heterocycle group attached to the moiety.

Starting molecular through an alkyl group, as defined herein. Representative examples of heterocycloalkyl groups include, 1,3-dioxolanyl, 1,3-benzodioxolylmethyl, 2,3-dihydro-1,4-benzodioxynylmethyl and 2,3-dihydrobenzofuranylmethyl.

The term "hydroxy" or "hydroxyl", as used herein, refers to -OH.

The term "hydroxyalkyl," as used herein, refers to an alkyl group that is substituted with at least one hydroxy group. Representative examples of hydroxyalkyl groups include, but are not limited to, 1-methyl1-hydroxyethyl and 1-hydroxyethyl.

15 The term "nitro", as used herein, refers to -NO2.

The term "nitroalkyl," as used herein, refers to an alkyl group substituted with at least one nitro group.

20 The term "oxo", as used herein, refers to = O.

The term "thioalkoxy", as used herein, refers to an alkyl group as defined herein, attached to the starting molecular moiety through a sulfur atom.

The term "thioalkoxyalkyl," as used herein, refers to a thioalkoxy group as defined herein, attached to the starting molecular moiety through an alkyl group as defined herein.

It will be understood that each of the alkanoyl terms, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylamino, alkylaminocarbonyl, alkynyl, aminoalkyl, aryl, arylalkyl, aryloxy, cyanoalkyl, cycloalkenyl, 30 cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, dialkylamino, dialkylaminocarbonyl, formylalkyl , haloalkenyl, haloalkoxy, haloalkyl, haloalkynyl, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocycle, heterocycloalkyl, heterocyclooxy, hydroxyalkyl, nitroalkyl, thioalkoxy and thioalkoxyalkyl used herein may be substituted

or without replacing.

In a first embodiment, the present invention provides a compound

, stereoisomer of the compound, ester of the compound, a pharmaceutically acceptable salt of the compound, a stereoisomer, or an ester, or a combination thereof in which:

The compound corresponds in structure to formula (II):

X is O; R1 is alkyl; R2 is selected from the group consisting of cycloalkylalkyl, cycloalkenyl alkyl, arylalkyl, heterocycloalkyl and

Heteroarylalkyl; R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkylalkyl, cycloalkenylalkyl, heterocycloalkyl, heteroarylalkyl, arylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkyl-alkyl-alkyl, alkyl-alkyl-alkyl -alkylSORa, -alkylSO2Ra, alkylNRaRb, -alkylC (= O) ORa, -alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) Ra, -alkylN (Rb) SO2Ra and

50 alkyl (Rb) SO2NRaRb, in which:

the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl moiety, cycloalkenyl moiety of the heterocycloalkyl moiety, heterocycle of the heterocycloalkyl moiety, heteroarylalkyl heteroaryl, and the aryl radical of the arylalkyl are substituted with 0, 1 or 2 independently selected among the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -SH, -S (alkyl), -S (haloalkyl), 5 SO2 (alkyl), -SO2 (haloalkyl) , -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, -C (= O) O (alkyl), -C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C ( = O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkyl S (alkyl), -alkylSO2 (alkyl), alkylNH2, -alkyl N (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylC (= O) OH, -alkylC (= O) O (alkyl), -alkylC ( = O) NH2, - alkylC (= O) N (H) (alkyl), - alkylC (= O) N (alkyl) 2,

10 C (= O) alkyl and R 3a;

R3a is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy and heterocyclooxy, in which

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, -SH, -S (alkyl ), -SO2 (alkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl , -C (= O) OH, C (= O) O (alkyl), -C (= O) NH2, -C (= O) N (H) (alkyl), -C (O) N (alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkyl SH, -alkyl (alkyl), -alkSO2 (alkyl), -alkyl NH2,

20 alkyl (H) (alkyl), -alkyl (alkyl) 2, -alkyl (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkyl C (= O) OH, alkylC ( = O) O (alkyl), -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl), -alkylC (= O) N (alkyl) 2 and -alkylC (= O) alkyl;

R4 is selected from the group consisting of:

A) -C (O) CH (R8) NHC (O) R9, b) -C (O) R9, c) -C (O) CH2-O-aryl, substituted with 0.1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2,

C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2, d) -C (O) CH2-O-heteroaryl, substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl , oxo, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, N (alkyl) 2, -C (= O) alkyl, -C ( = O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2,

35 e)

F)

9) h)

i)

5 j)

k)

and 10 l) -SO2R14;

R5 is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle, in which:

each of said substituents is substituted with 0, 1, 2 or 3 independently selected substituents

15 among the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, -ORa, -OC (= O) Ra, -SRa, -SORa, -SO2R3, -SO2NR3, -SO2R3, -NR3Rb, -N (Rb) NR3Rb, -N (Rb) C (= O) R3, -N (Rb) SO2R3, -N (Rb) C (= O) OR3, N (Rb) C (= O) NR3Rb, - N (Rb) SO2NR3Rb, -C (= O) Ra, -C (= O) NRaRb, -C (= O) ORa, azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylORa, -alkylOC (= O) Ra, - alkylSR3, -alkylSORa, -alkylSO2R3, -alkylSO2NRa, -alkylSO2ORa, alkylNR3Rb, -C (H) = N (OR3), -C (alkyl) = N (OR3), -C (H) = NNR3Rb, -C (alkyl ) = NNR3Rb, -C (H) = NOR3) NR3Rb,

20 C (alkyl) (= NOR3) NR3Rb, -alkylN (Rb) NRaRb, -alkylN (Rb) C (= O) Ra, -alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) NRaRb, -alkylN (Rb) SO2NRaRb, -alkylN (Rb) SO2Ra, -alkylC (= O) R3, -alkyl C (= O) OR3, -alkylC (= O) NR3Rb and R53; R5a is selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, in which:

each of said substituents is substituted with 0, 1, 2, 3 or 4 independently selected substituents

Among the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (H) (alkyl), -N (alkyl) 2, -SH, -S ( alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -N (H) C (= O) NH2, N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), C (= O) N (alkyl) 2, cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2, -alkyl N (H) (alkyl), alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylN (H) C (= O) NH2,

30 alkyl (H) C (= O) N (H) (alkyl), -alkyl (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -C1 alkyl (= O) NH2, C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2 alkyl;

R8 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl and arylalkyl, in which:

Each of said substituents is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, cyano, formyl, nitro, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (H) alkyl , N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) ( alkyl), -C (= O) N (alkyl) 2, C (= O) alkyl, hydroxyalkyl, alkoxy-alkyl, -alkyl NH2, -alkylN (H) alkyl, -alkylN (alkyl) 2, -alkylC (= O ) OH,

5 alkylC (= O) Oalkyl, -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl) and -alkylC (= O) N (alkyl) 2;

R9 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heterocycle, heteroaryl and OR9a, in which:

each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, N (H) alkyl , -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2;

R9a is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl and heterocycloalkyl, in which:

each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, N (H) alkyl , -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2;

R10 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl and heteroarylalkyl, wherein:

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, -SRa, -SORa, -SO2R3, -SO2NRaRb, -C (= O) Ra, -NRaRb, -N (Rb) C (= O) Ra, -N (Rb) C (= O) ORa, -N (Rb) SO2Ra, -N (Rb) SO2NRaRb, N (Rb) C (= NH) NRaRb, -N (Rb) C (= O) NRaRb, -C (= O) NRaRb and -C (= O) ORa;

R11 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R12 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R13 is selected from the group consisting of alkyl and haloalkyl; R14 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl and heterocycle,

35 in which:

each of said substituents is substituted with 0, 1, 2 or 3 independently selected substituents among the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, haloalkyl, -NH2, N (H) alkyl, -N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2;

Z is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Z 'is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Ra and Rb in each case are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, arylalkyl and heteroarylalkyl, in which:

Each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, -NH2, N ( H) (alkyl), -N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -N (H) C (= O) NH2, -N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), C (= O) N (alkyl) 2, -C ( = O) alkyl, cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkylNH2, -alkyl N (H) (alkyl), -alkylN (alkyl) 2, -alkyl N (H) C (= O) NH2, -alkylN ( H) C (= O) N (H) (alkyl), alkylN (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -alkylC (= O) NH2, -C1 (= O) N (H) (alkyl), C (= O) N (alkyl) 2 alkyl and -C (= O) alkyl; and n is 1,

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is alkyl and R4 is -C (O) C (H) (R8) NHC (O) R9.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is alkyl, R4 is C (O) C (H) (R8) NHC (O) R9 and R9 is -OR9a.

For example, the present invention provides a compound of formula (II), wherein X is O, R1, is alkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl and R9 is -OR9a.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is alkyl, R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl and R9 is -OR9a.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is alkyl, R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a and R2 is arylalkyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R 1 is alkyl; R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a , R9a is alkyl and R2 is arylalkyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R 1 is alkyl; R3 is

10 alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a, R9a is alkyl, R2 is arylalkyl and R5 is heteroaryl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl,

C4 alkyl or C5 alkyl; R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is alkyl, R2 is arylalkyl and R5 is heteroaryl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl,

C4 alkyl or C5 alkyl; R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is arylalkyl and R5 is heteroaryl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl,

C4 alkyl or C5 alkyl; R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl and R5 is heteroaryl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl,

C4 alkyl or C5 alkyl; R3 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl or heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl and R5 is thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, indazolyl, imidazopyridinyl, indolyl, benzimidazolyl, isoquinolinyl or quinolinyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is arylalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl and R5 is thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, indazolyl, imidazopyridinyl, indolyl, benzimidazolyl, isoquinolinyl or quinolinyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is arylalkyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl and R5 is thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, indazolyl, imidazopyridinyl, indolyl, benzimidazolyl, isoquinolinyl or quinolinyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is arylalkyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, indazolyl, imidazopyridinyl, indolyl, benzimidazolyl, isoquinolinyl or quinolinyl and R3a is heteroaryl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is phenylmethyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, indazolyl, imidazopyridinyl, indolyl, benzimidazolyl, isoquinolinyl or quinolinyl and R3a is pyridyl,

Thiazolyl or isoxaolyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is phenylmethyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is pyridyl and R3a is pyridyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is phenylmethyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is pyridyl substituted with an alkyl substituent and R3a is pyridyl.

For example, the present invention provides a compound of formula (III), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is phenylmethyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is pyridyl substituted with a methyl substituent and R3a is pyridyl.

For example, the present invention provides a compound of formula (II), wherein X is O, R1 is C3 alkyl, C4 alkyl or C5 alkyl; R3 is phenylmethyl substituted with R3a, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is C3 alkyl, C4 alkyl or C5 alkyl, R9 is -OR9a, R9a is methyl, R2 is phenylmethyl , R5 is 2-pyridyl substituted with a methyl substituent and R3a is 2-pyridyl.

Exemplary compounds of the present invention of formula (II) include, but are not limited to, those indicated below:

(1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- pyridinyl) ethyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl;

25 (1S, 2S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1.3 -thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl; 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4 tert-butyl-phenylbutyl] -2- [4 (2-pyridinyl) benzyl] hydrazinecarboxylate; (1S, 2S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2- il) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl ; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3.3

Methyl dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - ({2- (4-bromobenzyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2- methyl oxo-3- (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3 methyl -pyridinylmethyl) -1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl- Methyl 2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- Methyl (3-pyridinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S) -3,3-dimethyl-2- (3 - {[2- (5-methyl-3-isoxazolyl) - 1,3-thiazol-4-yl] methyl} -2-oxo-1

Methyl imidazolidinyl) butanoyl] amino} -2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S) -3,3-dimethyl-2- (2-oxo-3 - {[2- (3-pyridinyl) - 1,3-thiazol-4-yl] methyl} -1-imidazolidinyl) butanoyl] amino} 2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2 methyl dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3 - ((2-methyl- 1,3-thiazol-4-yl) 1,3-thiazol-4-yl-methyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl ) -2,2-dimethylpropylcarbamate of

55 methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S, 3S) -2- (3 - {[2- (2-ethyl-4-pyridinyl) -1,3- thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2 , Methyl 2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (2-pyridinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate;

65 (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(4-methyl-3-pyridinyl) ) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - [(2S, 3S) -3 - ({(2S) -3,3-dimethyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] butanoyl} amino) -2-hydroxy-4

Methyl phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3 -pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2- methyl dimethylpropylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {([(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4 -yl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-pyridazinylmethyl) -1-imidazolidinyl ] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (trifluoromethyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl ) pentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate

15 methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -2- {3 - [(2-isopropyl-1,3-thiazol-4-yl) methyl] -2-oxo-1-imidazolidinyl} -3,3dimethylbutanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] -4phenylbutyl} -2 - {[2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] - Methyl 2,2-dimethylpropylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3- thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazole- 4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino]

Methyl 4-phenylbutyl} -2 - {[2- (2-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole- Methyl 4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazol-4- il) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate methyl; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1, 3-Thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1,3- thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl;

35 (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazol-4 -yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2- [3-methyl-2- (2-oxo-1-pyrrolidinyl) butanoyl] -1- [ 4- (2-Pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} methyl pentanamide; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridazinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate;

45 (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -2- {3 - [(6-acetyl-2-pyridinyl) methyl] -2-oxo-1- methyl imidazolidinyl} -3,3-dimethylbutanoyl) amino] -2-hydroxy4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; 6 - [(3 - {(1S, 4S, 5S, 10S) -4-benzyl-1,10-diterc-butyl-5-hydroxy-2,9,12-trioxo-7- [4- (2-pyridinyl) ) benzyl] -13-oxa-3,7,8,11 tetraazatetradec-1-yl} -2-oxo-1-imidazolidinyl) methyl] -2-pyridinecarboxylate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - [(2S, 3S) -3-methyl-2- (2-oxo-1-imidazolidinyl)) pentanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3.3

Methyl dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) - 2-Pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2-Oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (8-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-4-quinolinyl) methyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(3-methyl-3H-imidazo) 4,5-b] pyridin-2-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridazinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(5-methyl-2-thienyl)) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] -4

Methyl phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6- methyl methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2-methylbutylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -3 - ({(2S, 3S) -2- [3 - ({2 - [(1S) -1- (acetylamino) ethyl] -1 , 3-thiazol-4-yl} methyl) -2-oxo-1-imidazolidinyl] -3methylpentanoyl} amino) -2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl ) Methyl -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {[(4S, 5R) -5-methyl-2-oxo-1,3-oxazolidin- 4-yl] carbonyl} -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1- imidazolidinyl} pentanamide; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl;

15 (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl)) -2-Pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} Methyl -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2,2-dimethyl-5-oxotetrahydro-3-furanyl) carbonyl] -1- [4- (2 -pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -2- [3- (imidazo [1,5-a] pyridin-3-ylmethyl) ) Methyl -2-oxo-1-imidazolidinyl] -3-methylpentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

25 (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {[(2S) -5-oxopyrrolidinyl] carbonyl} -1- [4- (2- pyridinyl) benzyl] hydrazino} propyl) -3methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] (3S) -4,4-dimethyl-2-oxotetrahydro-3-furanyl hydrazinecarboxylate; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] (3R) -4,4-dimethyl-2-oxotetrahydro-3-furanyl hydrazinecarboxylate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4il] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} - 2,2-dimethylpropylcarbamate of

35 methyl; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- methyl (methoxymethyl) -1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropyl-carbamate; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] -4phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate (3R) -2-oxotetrahydro-3-furanyl; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] -4phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate (3S) -2-oxotetrahydro-3-furanyl; (1S) -1 - [(2- [4- (diethylamino) benzyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - methyl [[6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S) -3,3-dimethyl-2- (2-oxo-1-imidazolidinyl) butanoyl] -1 - [4- (2-pyridinyl) benzyl] hydrazino}

2-Hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2 - (3 - {[6- (1-hydroxy-1-methylethyl) -2pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} - Methyl 2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} - Methyl 2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2 - (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2

Methyl pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(4,4-dimethyl-2-oxotetrahydro-3-furanyl) carbonyl] -1- [4- (2 -pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1 -hydroxy-1-methylethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- Methyl (1-hydroxy-1-methyl ethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

65 (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- ( hydroxymethyl) -2-pyridinyl] methyl} -2-oxo-1-imidazolidinyl) 3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- methyl (hydroxymethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1 -methylethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl;

5 (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1- hydroxy-1-methylethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2- methyl pyridinyl] methyl} -2-oxo-1-imidazolidinyl) 3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) - Methyl 2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2- methyl methyl-1,3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2-methylbutylcarbamate; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

15 (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (2-quinolinylmethyl)) Methyl -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2 - {[2- (3-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2, Methyl 2-dimethylpropylcarbamate; (1S) -1 - {[2-benzyl-2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[ 2- (3-Pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -2- [3- (imidazo [1 , Methyl 5-a] pyridin-3-ylmethyl) -2-oxo-1imidazolidinyl] -3-methylpentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate;

25 (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (imidazo [1, Methyl 5-a] pyridin-3-ylmethyl) -2-oxo-1-imidazolidinyl] 3,3-dimethylbutanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (imidazo [1,5-a] pyridin-3-ylmethyl) - Methyl 2-oxo-1-imidazolidinyl] -3,3-dimethylbutanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2- methyl oxo-3- (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1, Methyl 3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate; (1S, 2S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- Methyl (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate;

35 (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2 -isopropyl-1,3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6- methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2-isopropyl-1,3-thiazol-4- il) methyl] -2-oxo-1-imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2-isopropyl-1,3-thiazol-4- il) methyl] -2-oxo-1-imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-3-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate

45 methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3 -pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3 -pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2- oxo-3 - {[2- (3-pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(3-methylimidazo [1,5-a] pyridin- 1-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

55 (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(3 methyl methylimidazo [1,5-a] pyridin-1-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (1H-indazol-3-ylmethyl) -2-oxo-1- methyl imidazolidinyl] -3,3-dimethylbutanoyl} amino) -4phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (1H-indazol-3 -methyl) -2-oxo-1-imidazolidinyl] -3,3dimethylbutanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(6-isopropyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-indazol-3-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

65 (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1 -methyl-1H-indazol-3-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2- methyl-1H-benzimidazol-5-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -2- {3 - [(6-tert-butyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} -3,3-dimethylbutanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl;

5 (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole -4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate methyl; 4-hydroxy-2 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -1-pyrrolidinecarboxylate methyl; (1S, 2R) -2-hydroxy-1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) - 1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) propylcarbamate methyl; (1S) -1-cyclohexyl-2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1.3 -thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) 3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-methyl oxoethylcarbamate ;

15 (1S) -1-benzyl-2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1, 3-Thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-methyl oxoethylcarbamate ; (1S) -1- (cyclohexylmethyl) -2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1 , 3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-oxoethylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole- 4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Tert-Butyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate;

25 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino ) (3S) -tetrahydro-3-furanyl -4-phenylbutyl] -2 [4- (2-pyridinyl) benzyl] hydrazinecarboxylate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S) -3,3-dimethyl-2- (2-oxo-1-imidazolidinyl) butanoyl] -1 - [4- (2-Pyridinyl) benzyl] hydrazino} 2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2,6-dimethylphenoxy) acetyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} - 2-hydroxy-propyl) -3-methyl-2 [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - [(2-methylphenoxy) acetyl] -1- [4- (2-pyridinyl) benzyl] hydrazino } propyl) -3-methyl-2- [2oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2- (3-hydroxy-2-methylbenzoyl) -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2 [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide;

35 (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - [(2S, 3S) -3-methyl-2- (2-oxo-1-imidazolidinyl) ) pentanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S, 3S) -2- (2,4-dioxo-1-imidazolidinyl) -3-methylpentanoyl] - 1- [4- (2-Pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) Benzyl -4-phenylbutyl] -2 [4- (2-pyridinyl) benzyl] hydrazinecarboxylate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Ethyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -3- {2 - [(2S) -2- (acetylamino) -3,3-dimethylbutanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} -1-benzyl-2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide;

45 (1S, 2S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4- quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (3-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2- [4- (1,3-benzodioxol-5-yl) benzyl] -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S ) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2- [4- (3,5-dimethyl-4-isoxazolyl) benzyl] -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S ) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) ) -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (4-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate;

55 (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2) -pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-methyl dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (cyclohexylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6- methyl methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2-isobutylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (2-phenylethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

65 (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) ) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (2-thienylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (2-naphthylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-isopropylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

5 (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) ) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-isopropoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,4-dimethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (3-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (2-ethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (4-ethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate;

15 (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) ) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (3-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (trifluoromethyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-hydroxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (4-fluorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [3- (4-methylphenoxy) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- [3- (4-chlorophenoxy) benzyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (2-quinolinylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(5-ethyl-2-thienyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl- Methyl 2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (2-octinyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

6- (1 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} pentanoyl) amino] -4phenylbutyl} -2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazino) methyl hexanoate; (1S) -1 - [(2 - [(5-ethyl-2-furyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl- Methyl 2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (1H-imidazol-1-yl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- [4- (acetylamino) benzyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; 4 - [(1 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} pentanoyl) amino] -4phenylbutyl} -2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazino) methyl] methyl benzoate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (3-phenoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [3- (4-methoxyphenoxy) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-tert-butylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl;

55 (1S) -1 - [(2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S ) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- {4 - [(trifluoromethyl) sulfanyl] benzyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,7-dimethyl-6-octenyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2 - {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (cyclopropylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6- methyl methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(2-ethyl-1H-imidazol-5-yl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) - 3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo

Methyl 1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (2,3-dihydro-1-benzofuran-5-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3 methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] 2-oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-chlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,4-dimethoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3-fluoro-4-methoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- { Methyl 3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (1,3-benzodioxol-5-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2 - {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-methoxy-3-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (4-hydroxy-3-methoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- { Methyl 3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2-1 (2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1

Methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (methylsulfonyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (1H-imidazol-2-ylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (5-hydroxypentyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(4,5-dimethyl-2-furyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3- methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3-chlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate;

25 (1S) -1 - [(2- (3,5-dimethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - methyl [[6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2-neopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (1,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-cyanobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2-cyclohexyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl- Methyl 2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate;

35 (1S) -1 - [(2- (3,4-dichlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - methyl [[6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (4-pyridinyl) -1,3-thiazol-4-yl] methyl} methyl hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [3- (5-pyrimidinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4- methyl il] methyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate;

45 (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4 -yl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (2-pyridinyl) -1,3-thiazol-4-yl] methyl } hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - [(2-isopropyl-1,3-thiazol-4-yl) methyl] hydrazino} carbonyl) Methyl -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- Methyl 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,4-dimethoxybenzyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- methyl (methoxymethyl) -1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

55 (1S) -1 - {[2- (3,4-dimethylbenzyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2 - methyl ((methoxymethyl) -1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate; (1S, 2S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2- methyl pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2- pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] Methyl -2-oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate;

65 (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl ] Methyl -2-oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; Y

5 (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2) -pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-pyridinylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; or a pharmaceutically acceptable salt form, a stereoisomer, ester, salt of an ester, or a combination thereof.

In a second embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable salt form, a stereoisomer, ester, salt of an ester, or a combination thereof, and a pharmaceutically acceptable vehicle.

In a third embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable and one, two, three, four, five or six second HIV protease inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, steroisomer, ester, salt of an ester, or combination thereof pharmaceutically. acceptable and one, two, three, four, five or six seconds HIV protease inhibitors selected from the group consisting of ritonavir,

25 lopinavir, saquinavir, amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC -681, DPC-684 and GW640385X, and a pharmaceutically acceptable vehicle.

In a fourth embodiment, the present invention provides a pharmaceutical composition comprising a

Therapeutically effective amount of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable salt, steroisomer, ester, salt form or combination thereof, and one, two, three, four, five or six HIV reverse transcriptase inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising an amount

Therapeutically effective of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable salt, steroisomer, ester, salt form or combination thereof, and one, two, three, four, five or six HIV reverse transcriptase inhibitors selected from the group consisting of lamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210, Racivir (± -FTC), D-D4FC (Re-D4FC (Re-DTC) , DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirin,

Emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150, TMC-120 and TMC-125 and a pharmaceutically acceptable carrier.

In a fifth embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a salt form,

A stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable and one, two, three, four, five or six HIV entry / fusion inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a salt form,

50 stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable and one, two, three, four, five or six HIV entry / fusion inhibitors selected from the group consisting of enfuvirtide (T-20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C (SCH-C), Schering D (SCH-D), TNX-355 and UK-427857 and a pharmaceutically acceptable vehicle.

In a sixth embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, steroisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable and one, two, three, four, five or six HIV integrase inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable and one, two, three or four HIV integrase inhibitors selected from the group consisting of S-1360, zintevir (AR-177), L-870812 and L-870810 and a pharmaceutically acceptable carrier.

In a seventh embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable and one, two, three, four, five or six HIV budding / maturation inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable PA-457, and a pharmaceutically acceptable carrier.

In an eighth embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable, one, two or three second HIV protease inhibitors, one, two or three HIV reverse transcriptase inhibitors and a vehicle

15 pharmaceutically acceptable.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable, one, two or three

20 seconds HIV protease inhibitors selected from the group consisting of ritonavir, lopinavir, saquinavir, amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 ( AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC-684 and GW640385X, one, two or three HIV reverse transcriptase inhibitors selected from the group consisting of lamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210, Racivir (±

25 FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirine, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150, TMC -120 and TMC-125, and a pharmaceutically acceptable vehicle.

In a ninth embodiment, the present invention provides a pharmaceutical composition comprising a

Therapeutically effective amount of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable salt, steroisomer, ester, salt, or combination thereof, one, two or three second protease inhibitors of HIV, one, two or three HIV entry / fusion inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable, one, two or three seconds HIV protease inhibitors selected from the group consisting of ritonavir, lopinavir, saquinavir, amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP- 450),

40 JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC-684 and GW640385X, one, two or three HIV entry / fusion inhibitors selected from the group consisting of enfuvirtide (T- 20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C (SCH-C), Schering D (SCH-D), TNX-355 and UK427857 and a pharmaceutically acceptable vehicle.

In a tenth embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable, one, two or three second HIV protease inhibitors, one, two or three HIV integrase inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable, one, two or three seconds HIV protease inhibitors selected from the group consisting of ritonavir, lopinavir, saquinavir,

55 amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC -684 and GW640385X, one, two or three HIV integrase inhibitors selected from the group consisting of S-1360, zintevir (AR-177), L-870812 and L-870810, and a pharmaceutically acceptable carrier.

In an eleventh embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination of the same, pharmaceutically acceptable, one, two or three second HIV protease inhibitors, one, two or three HIV budding / modulation inhibitors and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof, pharmaceutically acceptable, one, two or three seconds HIV protease inhibitors selected from the group consisting of ritonavir, lopinavir, saquinavir,

5 amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC -684 and GW640385X and PA-457 and a pharmaceutically acceptable vehicle.

In a twelfth embodiment, the present invention provides the use of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable form of salt, stereoisomer, ester, salt of an ester, or combination thereof, to prepare a medicament. to inhibit the replication of HIV virus comprising contacting said virus with a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, steroisomer, ester, salt of a pharmaceutically acceptable ester or combination of the same.

In a thirteenth embodiment, the present invention provides use of pharmaceutical compositions as described hereinbefore to prepare a medicament for inhibiting HIV virus replication comprising contacting said virus with any one of the pharmaceutical compositions as described above. described earlier in this document.

In a fourteenth embodiment, the present invention provides the use of a compound or combination of compounds of formula (II) or a pharmaceutically acceptable form of salt, steroisomer, ester, salt of a ester, or combination thereof, to prepare a medicament. to treat or prevent an HIV infection comprising administering to a patient in need of such treatment a therapeutically effective amount of a

Compound or combination of compounds, of formula (II) or a pharmaceutically acceptable form of salt, stereoisomer, ester, salt of a ester or combination thereof.

In a fifteenth embodiment, the present invention provides use of pharmaceutical compositions as described hereinbefore to prepare a medicament for treating or preventing an HIV infection comprising administering to any patient in need of such treatment any one of the pharmaceutical compositions as They have been described earlier in this document.

In a sixteenth embodiment, the present invention provides the use of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of an ester, or combination thereof,

Pharmaceutically acceptable for preparing a medicament for inhibiting an HIV protease comprising contacting said HIV protease with a therapeutically effective amount of a compound or combination of compounds of formula (II) or a form of salt, stereoisomer, ester, salt of a pharmaceutically acceptable ester or combination thereof.

In a seventeenth embodiment, the present invention provides the use of pharmaceutical compositions as described hereinbefore to prepare a medicament for inhibiting an HIV protease comprising contacting said HIV protease with any one of the pharmaceutical compositions as described. described earlier in this document.

The term "N protecting group" or "N-protected", as used herein, refers to groups intended to protect the N-terminus of an amino acid or a peptide or to protect an amino group against unwanted reactions during synthetic procedures The commonly used N protecting groups are described in

T.H. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd edition, John Wiley & Sons, New York (1991). The N protecting groups comprise groups such as formyl, acetyl, propionyl, pivaloyl, t-butyl acetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, Similar; sulfonyl groups such as benzenesulfonyl, ptoluenesulfonyl and the like; sulfenyl groups, such as phenylsulfenyl (phenyl-S-), triphenylmethyl-sulfenyl (trityl-S-) and the like; sulfinyl groups, such as p-methylphenylsulfinyl (p-methylphenyl-S (O) -), t-butylsulfinyl (t-Bu-S (O) -) and the like; carbamate forming groups, such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxy

55-Benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro4,5-dimethoxycarbonyloxy-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2-nitro-4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2,4-dimethoxycarbonyl-2-nitro-4-dimethoxycarbonyl -trimetoxibenciloxicarbonilo, 1- (p-biphenylyl) -1-methylethoxycarbonyl, dimethyl-3,5dimetoxibenciloxicarbonilo, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloro-ethoxycarbonyl, phenoxycarbonyl , 4-nitro-phenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like; alkyl groups, such as benzyl, p-methoxybenzyl, triphenylmethyl, benzyloxymethyl and the like; p-methoxyphenyl and the like; and silyl groups, such as trimethylsilyl and the like. Preferred N protecting groups include formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butoxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).

65 As used herein, the expression configuration "S" and "R" is as defined by the IUPAC 1974 Recommendations in Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-30.

The compounds of the invention may comprise asymmetrically substituted carbon atoms. As a result, all stereoisomers of the compounds of the invention are intended to be included in the invention, including racemic mixtures, mixtures of diastereomers, as well as individual optical isomers, including, individual enantiomers and diastereomers of the compounds of the invention substantially free of their

5 enantiomers or other diastereomers. By "substantially free" refers to more than about 80% of other enantiomers or diastereomers of the compound, more preferably free more than about 90% of other enantiomers or diastereomers of the compound, even more preferably free of more than about 95 % of other enantiomers or diastereomers of the compound, even much more preferably free more than about 98% of other enantiomers or diastereomers of the compound and much more preferably free more than about 99% of other enantiomers or diastereomers of the compound.

In addition, the compounds comprising the possible geometric isomers of carbon double bonds and double carbon-nitrogen are also intended to be included in this invention.

The individual stereoisomers of the compounds of this invention can be prepared by any one of several methods that are within the skill of a person skilled in the art. These methods include stereospecific synthesis, chromatographic separation of diastereomers, chromatographic resolution of enantiomers, conversion of enantiomers in an enantiomeric mixture to diastereomers and then chromatographic separation of the diastereomers and regeneration of the individual enantiomers, enzymatic resolution and the like.

Stereospecific synthesis involves the use of appropriate chiral starting materials and synthetic reactions that do not cause racemization or reversal of stereochemistry in chiral centers.

The diastereomeric mixtures of the compounds obtained from a synthetic reaction can often be separated by chromatographic techniques that are well known to those skilled in the art.

Chromatographic resolution of enantiomers can be performed on chiral chromatography resins. Chromatography columns containing chiral resins are available in the market. In practice, the racemate is placed in the solution and loaded onto the column containing the chiral stationary phase. Then, the enantiomers were separated by HPLC.

The resolution of enantiomers can also be performed by converting the enantiomers of the mixture into diastereomers by reaction with chiral auxiliaries. Then, the resulting diastereomers can be separated by

35 column chromatography. This technique is especially useful when the compounds to be separated contain a carboxyl, amino or hydroxyl group that will form a salt or covalent bond with the chiral auxiliary. Chirally pure amino acids, organic carboxylic acids or organosulfonic acids are especially useful as chiral auxiliaries. Once the diastereomers have been separated by chromatography, the individual enantiomers can be regenerated. Frequently, the chiral auxiliary can be recovered and used again.

Enzymes, such as esterases, phosphatases and lipases, may be useful for the resolution of derivatives of enantiomers in an enantiomeric mixture. For example, an ester derivative of a carboxyl group can be prepared in the compounds to be separated. Certain enzymes will selectively hydrolyze only one of the

45 enantiomers in the mixture. Then, the resulting enantiomerically pure acid can be separated from the non-hydrolyzed ester.

In addition, the solvates and hydrates of the compounds of formula (I), (II), (III), (IV) or (V), are intended to be included in this invention.

When any variable (for example A, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, Ra, Rb, Rc, n, Z, Z ', X , Y, etc.) appears more than once in any substituent or in the compound of formula (I), (II), (III), (IV) or (V),

or any other formula in this document, its definition in each case depends on its definition in each different case. In addition, substituent combinations are only allowed if such combinations give as

55 result stable compounds. Stable compounds are compounds that can be isolated in a useful degree of purity from a reaction mixture.

The compounds of the present invention can be used in the form of salts obtained from inorganic or organic acids. These salts include, but are not limited to, those listed below: 4-acetamido-benzoate, acetate, adipate, alginate, carbonate, 4-chlorobenzenesulfonate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, canforate, camphorsulfonate, colato , digluconate, cyclopentanepropionate, dichloroacetate, dodecylsulfate, ethanedisulfonate, ethanesulfonate, ethylsuccinate, formate, fumarate, galactarate, D-gluconate, Dglucuronato, glucoheptanoate, glutarate, licerofosfato, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate (isethionate), 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, lactate, 65 lactobionate, laurate, maleate, malonate, mandelate, methanesulfonate, nicotinate, 1,5-naphthalene disulfonate, 2naphthalenesulfonate, oléate, oxalate , pamoate, palmitate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate,

propionate, L-pyroglutamate, sebacate, stearate, succinate, tartrate, terephthalate, thiocyanate, p-toluenesulfonate, undecanoate, undecylenate and valerate. In addition, the groups containing basic nitrogen can be quaternized with said agents such as lower alkyl halides, such as chlorides, bromides and iodides of methyl, ethyl, propyl and butyl; dialkyl sulfates, such as dimethyl, diethyl, dibutyl and diamyl sulfates, long chain halides, such

5 such as chlorides, bromides and iodides of decyl, lauryl, myristyl and stearyl, aralkyl halides, such as benzyl and phenethyl bromides, and others. In this way, products soluble or dispersible in water or oil are obtained.

Examples of acids that can be used to form pharmaceutically acceptable acid addition salts include said inorganic acids, such as hydrochloric acid, sulfuric acid and phosphoric acid, and said organic acids, such as oxalic acid, maleic acid, succinic acid and acid. citric. Other salts include salts with alkali metals or alkaline earth metals, such as aluminum, sodium, lithium, potassium, calcium, magnesium or zinc, or with organic bases, such as diethyl ethanolamine, diethanolamine, ethylenediamine, guanidine, meglumine, olamine (ethanolamine), piperazine , piperidine, triethylamine, tromethamine, benzathine, benzene-ethanamine, adenine, cytosine, diethylamine, glucosamine, guanine, nicotinamide, hydrabamine, tributylamine, deanol, epolamine or

15 triethanolamine.

Representative salts of the compounds of the present invention include, but are not limited to, hydrochloride, methanesulfonate, sulfonate, phosphonate, isethionate and trifluoroacetate.

The compounds of the present invention can also be used in the form of prodrugs (not claimed). Examples of such prodrugs include compounds in which one, two or three hydroxy groups in the compound of this invention are functionalized with R 15, in which R15 is

or

wherein R103 is C (R105) 2, O or -N (R105); R104 is hydrogen, alkyl, haloalkyl, alkoxycarbonyl, aminocarbonyl,

Alkylaminocarbonyl or dialkylaminocarbonyl, each M is independently selected from the group consisting of H, Li, Na, K, Mg, Ca, Ba, -N (R105) 2, alkyl, alkenyl and R106; in which 1 to 4 -CH2 radicals of the alkyl

or alkenyl, other than the -CH2 radical that is attached to Z ", is optionally replaced by a heteroatom group selected from the group consisting of O, S, S (O), SO2 and N (R105); and in which any hydrogen in said alkyl, alkenyl or R106 is optionally replaced with a substituent selected from the group consisting

30 in oxo, -OR105, -R105, -N (R105) 2, -CN, -C (O) OR105, -C (O) N (R105) 2, -SO2N (R105), -N (R105) C (O) R105, -C (O) R105, -SR105, S (O) R105, -SO2R105, -OCF3, -SR106, -SOR106, -SO2R106, -N (R105) SO2R105, halo, -CF3 and NO2; Z "is CH2, O, S, -N (R105), or, when M is absent, H; Q is O or S; W is P or S; where when W is S, Z" is not S;

35 M 'is H, alkyl, alkenyl or R106; wherein from 1 to 4 -CH2 radicals of the alkyl or alkenyl are optionally replaced by a heteroatom group selected from O, S, S (O), SO2 or N (R105); and wherein any hydrogen in said alkyl, alkenyl or R106 is optionally replaced by a substituent selected from the group consisting of oxo, -OR105, -R105, -N (R105) 2, -CN, -C (O) OR105 , -C (O) N (R105) 2, -SO2N (R105), -N (R105) C (O) R105, -C (O) R105, -SR105, -S (O) R105, -SO2R105, - OCF3, -SR106, -SOR106, -SO2R106, -N (R105) SO2R105, halo, -CF3 and NO2;

R106 is a monocyclic or bicyclic ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle; wherein any of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO2 and N (R105); and wherein any of said ring system is substituted with 0, 1, 2, 3, 4, 5 or 6 substituents selected from the group consisting of hydroxy, alkyl, alkoxy and -OC (O) alkyl;

Each R105 is independently selected from the group consisting of H or alkyl; wherein said alkyl is optionally substituted with a ring system selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle; wherein any one of said heteroaryl and heterocycle ring systems contains one or more heteroatoms selected from the group consisting of O, N, S, SO, SO2, and N (R105); and in which any of one of said ring systems is substituted with 0, 1, 2, 3 or 4 substituents selected

50 between the group consisting of oxo, -OR105, -R105) -N (R105) 2, -N (R105) C (O) R105, -CN, -C (O) OR105, -C (O) N ( R105) 2, halo and -CF3; q is 0 or 1; m is 0 or 1; and t is 0 or 1.

Representative examples of R15 of formula (VI) or (VII) that can be used for the functionalization of hydroxy groups in the compound of the present invention include, but are not limited to, those indicated below:

, - (L) -lisin, -PO3Na2,

, - (L) -tyrosine,

-

PO3-Mg,

-

PO3 (NH4) 2, -CH2-OPO3Na, - (L) -serine,

-

SO3-Na2,

- (L) -valine, - (L) -glutamic acid, - (L) -aspartic acid, - (L) -γ-tert-aspartic acid,

15 - (1L- (L) -3-pyridylalanine, - (L) -histidine, -CHO, -C (O) CF3. -PO3K2, -PO3Ca, -PO3-spermine, -PO3- (spermidine) 2, - PO3- (maglamine) 2,

Y

It will be understood by those skilled in the art that the M or M 'component in the formulas set forth herein will have a covalent, covalent / zwitterionic or ionic association with Z "or R103 depending on the actual choice for M or M'. When M or M 'is hydrogen, alkyl, alkenyl or R106, then M or M', are covalently linked to -R103 or Z ". If M is a mono or bivalent metal or other charged species (ie NH4 +), there is a

Ionic interaction between M and Z "and the resulting compound is a salt.

These prodrugs of the compound of the present invention act to increase the solubility of these compounds in the gastrointestinal tract. These prodrugs also act to increase the solubility for intravenous administration of the compound. These prodrugs can be prepared using conventional synthetic techniques. One skilled in the art will be well aware of conventional synthetic reagents to convert one or more of the hydroxy groups of the compounds of the present invention to a desired prodrug, functionalized by the substituents of formula (VI) or (VII) as defined. previously.

The prodrugs of the compounds of the present invention are metabolized in vivo to provide the compound of the present invention.

The compounds of the invention are useful for inhibiting retroviral protease, in particular HIV protease, in vitro or in vivo (especially in mammals and in particular in humans). The compounds of the present invention are also useful for the inhibition of retroviruses in vivo, especially human immunodeficiency virus (HIV). The compounds of the present invention are also useful for the treatment or prophylaxis of diseases caused by retroviruses, especially acquired immunodeficiency syndrome or an HIV infection in a human or other mammal.

The daily dose administered to a human being or other human host in single or divided doses may be in amounts, for example, from 0.001 to 300 mg / kg of body weight daily and more usually from 0.1 to 20 mg / kg of body weight daily. The unit dosage compositions may contain such amounts or submultiples thereof to make up the daily dose.

The amount of active ingredient that can be combined with the carrier materials to produce a simple dosage form will vary depending on the host treated and the particular mode of administration.

It will be understood, however, that the specific dose level for any particular patient will depend on a variety of factors including activity of the specific compound employed, age, body weight, health.

25 general, sex, diet, time of administration, route of administration, excretion rate, drug combination and the severity of the particular disease undergoing therapy.

The compounds of the present invention can be administered orally, parenterally, sublingually, by inhalation spray, rectally or topically in unit dosage formulations containing conventional pharmaceutically acceptable excipients, adjuvants and non-toxic vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches.

or iontophoresis devices. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known technique using suitable dispersing agents or humectants and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-propanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils are conventionally employed as a solvent or suspending medium. Any insipid fixed oil including synthetic mono- or diglycerides can be used for this purpose. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Suppositories for rectal administration of the drug can be prepared by mixing the drug with an excipient.

Suitable non-irritant such as cocoa butter and polyethylene glycols that are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug.

Solid dosage forms for oral administration may include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert diluent such as sucrose lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, for example lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills with enteric coatings can be additionally prepared.

Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents and sweetening, flavoring and perfuming agents.

The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multilamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present liposome-shaped compositions may contain, in addition to the compound of the present invention, stabilizers, preservatives, excipients and the like. Preferred lipids are phospholipids and phosphatidyl hills

(lecithins), both natural and synthetic.

Methods for forming liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33.

Although the compound of the invention can be administered as the sole active pharmaceutical agent, it can also be used in combination with one or more immunomodulators, antiviral agents, other anti-infective agents or vaccines. Other antiviral agents to be administered in combination with a compound of the present invention include AL-721, beta interferon, polyanoacetate, reverse transcriptase inhibitors (eg, BCH-189, AzdU, carbovir, ddA, d4C, d4T (stavudine), 3TC (lamivudine) DP-AZT, FLT (fluorothimidine), BCH-189, 5-halo-3'-thiadideoxycytidine, PMEA, bis-POMPMEA, zidovudine (AZT), MSA-300, trovirdine, R82193, L-697,661, BI- RG-587 (nevirapine), abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210, Racivir (± -FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine , efavirenz, capravirin, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150, TMC-120 and TMC-125 and the like), inhibitors of

15 retroviral protease (for example, HIV protease inhibitors such as ritonavir, lopinavir, saquinavir, amprenavir (VX-478), fosamprenavir, nelfinavir (AG1343), tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir ( DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681, DPC-684, GW640385X, SC52151, BMS 186,318, SC-55389a, BILA 1096 BS, DMP-323, KNI -227 and the like), compounds of HEPT, L, 697,639, R82150, U-87201E and the like), HIV integrase inhibitors (S-1360, zintevir (AR-177), L-870812 L-870810 and the like), TAT inhibitors (e.g. RO-24-7429 and the like), trisodium phosphonoformate, HPA-23, eflonitin, T-Peptide, Reticulose (nucleophosphoprotein), ansamycin LM 427, trimetrexate, UA001, ribavirin, alpha interferon, oxetanocin- G, cilobut-G, cyclobut-A, ara-M, BW882C87, foscarnet, BW256U87, BW348U87, L693,989, BV ara-U, CMV triclonal antibodies, FIAC, HOE-602, HPMPC, MSL-109, TI- 23, trifluridine, vidarabine, famciclov go, penciclovir, acyclovir, gancichlor, castanosperminem rCD4 / CD4-IgG, CD4-PE40, butyl-DNJ,

Hypericin, oxamyristic acid, dextran sulfate and pentosan polysulfate. Other agents that can be administered in combination with the compound of the present invention include HIV entry / fusion inhibitor (eg enfuvirtide (T-20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C (SCH-C), Schering D (SCH-D), TNX-355, UK-427857 and the like) and HIV germination / modulation inhibitor such as PA-457. Immunodductors that can be administered in combination with the compounds of the present invention include bropyrimine, Ampligen, anti-human alpha interferon antibody, colony stimulating factor, CL246,738, Imreg-1, Imreg-2, diethylthiocarbamate, interleukin-2, interferon alpha , inosine pranobex, methionine encephalin, muramil-tripeptide, TP-5, erythropoietin, naltrexone, tumor necrosis factor, beta interferon, gamma interferon, interleukin-3, interleukin-4, CD8 + infusion, interferon alpha immunoglobulin, IGF-1, anti-Leu-3A, self-vaccination, biostimulation, extracorporeal photophoresis, cyclosporine, rapamycin, FK-565,

35 FK-506, G-CSF, GM-CSF, hyperthermia, isopinosine, IVIG, HIVIG, passive immunotherapy and hyperimmunization with polio vaccine. Other anti-infective agents that can be administered in combination with the compound of the present invention include pentamidine isethionate. Any of a variety of HIV or AIDS vaccines can be used (e.g., gp120 (recombinant), Env 2-3 (gp120), HIVAC-1e (gp120), gp160 (recombinant), VaxSyn HIV-1 (gp160), Immuno -Ag (gp160), HGP-30, Immunogen-HIV, p24 (recombinant), VaxSyn HIV-1 (p24)) in combination with the compound of the present invention.

Other agents that can be used in combination with the compound of the present invention are ansamycin LM 427, apurinic acid, ABPP, Al-721, carrisin, AS-101, avarol, azimexone, colchicine, compound Q, CS-85, N-acetyl cysteine, (2-oxothiazolidin-4-carboxylate), D-penicillamine, diphenylhydantoin, EL-10, erythropoietin, fusidic acid,

45 glucan, HPA-23, human growth hormone, hydroxychloroquine, iscador, L-ofloxacin or other antibiotics of quinolone, lentinan, lithium carbonate, MM-1, monolaurin, MTP-PE, naltrexone, neurotropin, ozone, PAI, panax ginseng, pentophyllin, pentoxifylline, Peptide T, conifer pineapple extract, polyamanoacetate, reticulous, retrogenous, ribavirin, ribozymes, RS-47, Sdc-28, silicotungstate, THA, thymic humoral factor, thimopentine, thymosin fraction 5, alpha thymosin one, thymostimulin, UA001, uridine, vitamin B 12 and wobe-mugos.

Other agents that can be used in combination with the compound of the present invention are antifungals such as amphotericin B, clotrimazole, flucytosine, fluconazole, itraconazole, ketoconazole and nystatin and the like.

Other agents that can be used in combination with the compound of the present invention are antibacterial.

55 such as amicacin sulfate, azithromycin, ciprofloxacin, tosufloxacin, clarithromycin, clofazimine, ethambutol, isoniazid, pyrazinamide, rifabutin, rifampin, streptomycin and TLC G-65 and the like.

Other agents that can be used in combination with the compound of the present invention are anti-neoplastic agents such as interferon alfa, COMP (cyclophosphamide, vincristine, methotrexate and prednisone), etoposide, mBACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone) , PRO-MACE / MOPP (prednisone, methotrexate (with leucovine rescue), doxorubicin, cyclophosphamide, taxol, etoposide / mechlorethamine, vincristine, prednisone and procarbazine), vincristine, vinblastine, angioinhibins, pentosan polyserium 4-PG and the like

Other agents that can be used in combination with the compound of the present invention are drugs for treating neurological disease such as peptide T, ritalin, lithium, elavil, phenytoin, carbamazipine, mexitetin, heparin and cytosine arabinoside and the like.

Other agents that can be used in combination with the compound of the invention are anti-protozoa such as albendazole, azithromycin, clarithromycin, clindamycin, corticosteroids, dapsone, DIMP, eflornithine, 566C80,

5 fansidar, furazolidone, L, 671,329, letrazuril, metronidazole, paromycin, pefloxacin, pentamidine, piritrexim, primaquine, pyrimethamine, somatostatin, spiramycin, sulfadiazine, trimethoprim, TMP / SMX, trimetrexate and WR 6026 and the like.

For example, a compound of the present invention can be administered in combination with ritonavir. Such a combination is especially useful for inhibiting HIV protease in a human being. Such a combination is also especially useful for inhibiting or treating an HIV infection in a human being. When used in such a combination the compound of the present invention and ritonavir can be administered as separate agents at the same or different times or can be formulated as a simple composition comprising both compounds.

When administered in combination with a compound or combination of compounds of the present invention, ritonavir causes an improvement in pharmacokinetics (i.e., increases half-life, increases time to peak plasma concentration, increases blood levels ) of the compound of the present invention.

Another combination may comprise a compound, or combination of compounds of the present invention with ritonavir and one or more reverse transcriptase inhibitors (e.g., lamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine , MIV-210, Racivir (± -FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirine, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC -961, MIV-150 TMC-120, TMC-125 and the like). A further combination may comprise a compound, or combination of compounds of the present invention with ritonavir and one or more

25 HIV entry / fusion inhibitors. Such combinations are useful for inhibiting or treating an HIV infection in a human being. When used in such a combination the compound or combination of compounds of the present invention and ritonavir and one or more reverse transcriptase inhibitors or HIV entry / fusion inhibitors can be administered as separate agents at the same or different times or can be formulated as Compositions comprising two or more of the compounds.

It will be understood that agents that can be combined with the compound of the present invention for the inhibition, treatment or prophylaxis of AIDS or an HIV infection are not limited to those listed above, but in principle include any agent useful for treatment or prophylaxis of AIDS or an HIV infection.

When administered as a combination, the therapeutic agents can be formulated as separate compositions that are provided at the same time or at different times or the therapeutic agents can be provided as a simple composition.

Antiviral activity

Determination of activity against wild-type HIV or variants with passes

MT4 cells with multiplicity of infection (MOI) 0.003 of wild-type HIV or mutant variants with passages at 1 X 10 6 cells / ml for 1 hour were infected, washed twice to remove non-absorbed virus and resuspended at 1 X 105 cells / ml of medium, seeded in a 96-well plate at 100 µl / well and treated with an equal volume of inhibitor solution in a series of semi-logarithmic dilutions in RPMI 1640 medium (Rosewell Park Memorial Institute) ( Gibco) containing 10% fetal bovine serum (FBS), in triplicate. The final concentration of DMSO in all wells was 0.5%. The virus control culture was treated in an identical manner except that no inhibitor was added to the medium. The cell control was incubated in the absence of inhibitor or virus. The plates were incubated for 5 days in a CO2 incubator at 37 ° C. On day 5, 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT) stock solution (4 mg / ml in PBS, Sigma Cat. No. M 5655) was added to each well at 25 μl per well. The plates were further incubated for 4 hours, then treated with 20% sodium dodecyl sulfate (SDS) plus 0.02 N HCl at 50 µl per well to lyse the cells. After an overnight incubation, an optical density (D.O.) was measured by reading the plates at wavelengths of 570/650 nm at

55 a Bio-Tek microtiter plate reader. The reduction in percentage cytopathic effect (CPE) was calculated from the following formula:

((D.O. test well -D.O. infected control well) / (D.O. uninfected control well -D.O. infected control well)) X 100

The EC50 values were determined from the representation of the logarithm of (Fa / Fu) versus logarithm of (compound concentration) using the equation of effect of the median (Chou, 1975, Proc. Int. Cong. Pharmacol. 6th p. 619) in which Fa is the fraction inhibited by the compound and Fu is the uninhibited fraction (1-Fa).

When tested by the above method, the compounds of the present invention show EC50 in the range of 1 nM to 100 nM.

Determination of anti-HIV activity in the presence of human serum

The previous antiviral assay was performed in 96-well tissue culture plates containing 50% human serum (HS) (Sigma) plus 10% FBS (Gibco / BRL, Grand Island, NY). The compounds were dissolved in DMSO, diluted 5 to semi-logarithmic concentrations in DMSO, then transferred to serum-free medium at four times the final concentration. These solutions were added to 96-well plates at 50 µl per well, in triplicate. Cells were infected separately with 0.001 HIV MOI 1 to 1 X 10 6 cells / ml for 1 hour, washed twice to remove non-adsorbed virus and resuspended to 2 X 10 5 cells / ml of serum-free medium. The cell suspension (50 μl) was seeded at 1 X 104 cells per well. Uninfected cells were included as a control. The

The final DMSO concentration in all wells was 0.5% including infected and non-infected control wells. The cultures were incubated for 5 days in a CO2 incubator at 37 ° C. EC50 values were measured using MTT uptake as described above.

When tested by the above method, the compounds of the present invention show EC50 in the range 15 of 5 nM to 1 µM.

Generation of HIV resistant to ABT-378 / r (A17) by in vitro pass

MT4 cells (2x106) were infected with pNL4-3 at an MOI of 0.03 for 2 hours, washed, then cultured

20 in the presence of ABT-378 and ritonavir at a concentration ratio of 5: 1. The concentration of ABT-378 and ritonavir used in the initial pass was 1 nM and 0.2 nM respectively. Viral replication was monitored by determination of p24 antigen levels in the culture supernatant (Abbott Laboratories) as well as by observation of any cytopathic effect (CPE) present in the cultures. When p24 antigen levels were positive, the viral supernatant was collected for the next pass. After each pass, the drug concentrations in the

25 subsequent pass were gradually increased. After 5 months of selection, ABT-378 1.5 μM can be used in the final pass. The A17 virus was generated after 17 passes of pNL4-3 in the presence of ABT-378 and ritonavir at a concentration ratio of 5: 1.

When tested by the above method, the compounds of the present invention inhibit the A17 virus with EC50 in the range of 1 nM to 1 µM.

Synthetic Methods

The abbreviations that have been used in the descriptions of the schemes and the examples given to

35 are: DMF is N, N-dimethylformamide, DMSO is dimethyl sulfoxide, THF is tetrahydrofuran, TEA is triethylamine, NMMO is 4-methylmorpholine N-oxide, HOBT is 1-hydroxybenzotriazole hydrate, DCC is 1,3-cyclohexylcarbodiimide, EDAC is chloro of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, DMAP is 4 (dimethylamino) pyridine, TFA is trifuoroacetic acid, DEPBT is 3- (diethoxyphosphoryloxy) -1,2,3-benzotriazin-4 (3H) -one, DPPA is diphenylphosphine azide, NMM is N-methylmorpholine, DIBAL is diisobutyl aluminum hydride, EtOAc is acetate

40 ethyl and TBAF is tetrabutyl ammonium fluoride.

The compounds and processes of the present invention will be better understood together with the following synthetic schemes illustrating the methods by which the compounds of the invention can be prepared. The starting materials can be obtained from commercial sources or can be prepared by methods

45 established bibliographies known to those skilled in the art. Groups A, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, X, Y, Z, Z ', Ra, Rb, Rc and n are as have been defined above unless otherwise indicated below.

This invention is intended to include compounds having the formula (I), (II), (III), (IV) or (V) when prepared

50 by synthetic processes or by metabolic processes. The preparation of the compounds of the invention by metabolic processes includes those that occur in the human or animal body (in vivo) or processes that occur in vitro.

The compounds of the invention can be prepared according to the methods described in Schemes 1-3, which are shown below.

Scheme 1

The amino acid esters of formula (1), wherein P2 is lower alkyl (for example methyl, ethyl, tert-butyl and

5), they can be treated with a suitably protected aldehyde of formula (2) (for example, P10 and P11 together with the nitrogen atom to which they are attached form a phthalimido group) in the presence of a reducing agent under acidic conditions (for example , in the presence of acetic acid or hydrochloric acid) in an inert solvent, or mixture of solvents, such as DMSO, methanol, dichloromethane, and the like, at a temperature of about room temperature to about 50 ° C, to provide compounds of formula ( 3). The examples of

Reducing agents include, but are not limited to, sodium triacetoxyborohydride, sodium borohydride, sodium cyanoborohydride and BH3-pyridine.

Removal of the phthalimido group can be achieved using hydrazine in a suitable solvent, such as ethanol and the like, at a temperature of about room temperature to about 100 ° C, to

15 provide compounds of formula (4).

Compounds of formula (4) can be converted to compounds of formula (5) (a) by treating compounds of formula (4) with an aldehyde having the formula R5CHO, optionally in the presence of a drying agent (e.g., sulfate of magnesium, silica gel and the like) in an inert solvent, or solvent mixture, such as

Dichloromethane, benzene, toluene, methanol, ethanol, DMSO, and the like, at a temperature of about room temperature to about 100 ° C, and (b) reacting the product of step (a) with a reducing agent at about room temperature. Examples of the reducing agent include, but are not limited to, sodium triacetoxyborohydride, sodium borohydride, sodium cyanoborohydride and BH3-pyridine.

The diamine of formula (5) can be treated with a carbonylating agent in an inert solvent, or solvent mixture, such as dichloromethane, 1,2 dichloroethane, toluene, acetonitrile, and the like, at a temperature of about room temperature to approximately 100 ° C, to provide compounds of formula (6). Examples of the carbonylation agent include, but are not limited to, 4-nitrophenyl carbonate, phosphene, diphosgene, triphosgene, carbonyl diimidazole and disuccinimidyl carbonate.

The conversion of the compounds of formula (6) into the corresponding acids having the formula (7) can be achieved by acid hydrolysis (for example, acetic acid, trifluoroacetic acid, toluenesulfonic acid, formic acid, hydrochloric acid and the like) or hydrolysis of bases (for example sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, and the like) in a solvent, or mixture of solvents, such as DMF,

Toluene, benzene, dichloromethane, ethyl acetate, water, methanol and the like, at a temperature of about 0 ° C to about 100 ° C.

Scheme 2

The amino acid esters having the formula (1), in which P2 is lower alkyl (for example, methyl, ethyl, tert-butyl and the like) can be treated with compounds of the formula P1OC (O) CH2X, in which P1 is an alkyl lower and X

5 is Br, Cl or I, in an inert solvent, or mixture of solvents, such as DMF, dichloromethane, 1,2-dichloroethane, acetonitrile, toluene, benzene, diethyl ether and the like, at a temperature of about room temperature to approximately 50 ° C, to provide (8).

The compounds of formula (8) can be converted into compounds of formula (9) by (a) treatment with

Chlorosulfonyl isocyanate (or compounds of formula XSO2NCO, wherein X is Br, Cl, or I, and the like) in an inert solvent, or mixture of solvents, such as dichloromethane, 1,2-dichloroethane, dioxane, toluene, DMF, THF diethyl ether and the like, at a temperature of about -10 ° C at about room temperature, and (b) treatment of the product of step (a) with water at about room temperature. Alternatively, (8) can be reacted with a carbonylation agent, such as, but not limited to, carbonate of

4-Nitrophenyl, phosphene, diphosgene, triphosgene, carbonyl diimidazole, disuccinimidyl carbonate, followed by reaction with ammonia.

Cyclization of the compounds of formula (9) to provide compounds of formula (10) can be achieved by treatment with an organic amine base, such as triethyl amine, diisopropylethyl amine, imidazole, pyridine,

N-methylmorpholine and the like, or an inorganic base, such as sodium bicarbonate, sodium carbonate, cesium carbonate and the like, in an inert solvent, or solvent mixture, such as methanol, ethanol, DMF, dioxane, xylene, THF and similar, at a temperature of about room temperature to about 70 ° C.

The imides of formula (10) can be converted to the compounds of formula (12) by (a) deprotonation with

25 a base in an inert solvent, or mixture of solvents, such as dichloromethane, 1,2-dichloroethane, THF, diethyl ether, tert-butyl methyl ether, and the like, at a temperature of about -78 ° C to about 0 ° C, Y

(b) treating the product of step (a) with an alkyl halide of formula (11), wherein X is Cl, Br or I, at a temperature of about room temperature to about 100 ° C. Examples of the base include, but are not limited to, sodium hydride, potassium hydride, lithium diisopropyl amide, lithium bis (trimethylsilyl) amide.

Alternatively, the compounds of formula (10) can be converted into the compounds of formula (12) by treatment with an alcohol having the formula R7CH2OH, in the presence of triphenylphosphine and diethyl azodicarboxylate, in an inert solvent, such as dichloromethane, THF, dioxane or DMF, at a temperature of about 0 ° C to about 25 ° C.

The compounds of formula (12) can be converted into the compounds of formula (13) using the conditions for the transformation of the compounds of formula (6) into the compounds of formula (7).

Scheme 3

The compounds of formula (15), wherein R 8 is an alkyl or substituted alkyl moiety can be treated with an organic amine base, such as, but not limited to, triethylamine, diisobutylethylamine, pyridine, 2-methylimidazole, pyrrole and N5 methylmorpholine, and a chloroformate of formula R93OC (O) Cl (for example methyl chloroformate and the like) to give compounds of the formula (16). Compound (16) is treated with tert-butyl carbazate in the presence of an activating agent that includes, but is not limited to, 1,1'-carbonyldiimidazole (CDI), 1,3-dicyclohexylcarbodiimide (DCC), 1,3-diisopropylcarbodiimide, 1- (3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDAC), DEPBT (3 (diethoxyphosphoryloxy) -1,2,3-benzotriazin-4 (3H) -one), PyBOP (benzotriazol-1-yl- hexafluorophosphate oxy-tris-pyrrolidino

10 phosphonium), and 1,3-di-tert-butylcarbodiimide to provide the compound of formula (17). Deprotection of the compound (17) with acids, such as, but not limited to, hydrochloric acid gives the compound (18).

Treatment of the compound (18) with an aldehyde having the formula R3CHO provides a hydrazone which, in turn, is reduced with hydrogen gas using a metal catalyst, such as, but not limited to, palladium, platinum or rhodium on carbon in presence of an alcoholic solvent, such as methanol or ethanol, to give the compound (19).

The epoxides of formula (20) can be treated with a hydrazine, such as, the compound (19) in an alcoholic solvent, such as, but not limited to, ethanol or methanol at a temperature of about 25 ° C at

About 80 ° C, to give compounds of formula (21). The compound (21) can be deprotected using acids, such as, but not limited to, hydrochloric acid to give the compound (23). Alternatively compounds of formula (21) can be treated with hydrogen gas using a metal catalyst, such as, but not limited to, palladium, platinum or rhodium on carbon in the presence of an alcoholic solvent, such as methanol or ethanol to give the compound (22 ).

The compounds of formula (23) can also be obtained from the compounds of formula (18) by (a) treating compounds of formula (18) with compounds of formula (20) to give compounds of formula (22), using the conditions for the transformation of (19) into (21), (b) the treatment of compounds of formula (22) with an aldehyde of formula R3CHO, optionally in the presence of a drying agent (eg, sulfate of

30 mg, silica gel and the like) in an inert solvent, or mixture of solvents, such as dichloromethane, benzene, toluene, methanol, ethanol, methylsulfoxide, and the like, at a temperature of about room temperature to about 100 ° C, and (c) the reaction of the product of step (b) with a reducing agent at approximately room temperature. Examples of the reducing agent include, but are not limited to, sodium triacetoxyborohydride, sodium borohydride, sodium cyanoborohydride and BH3-pyridine.

5 Tert-butyl carbazate can be treated with aldehydes of formula R3CHO to form a hydrazone which, in turn, is reduced with hydrogen gas using a metal catalyst, such as, but not limited to, palladium, platinum or rhodium on carbon in the presence of an alcoholic solvent, such as methanol or ethanol, to give compounds of formula (25). The compounds of formula (25) can be reacted with epoxides of formula (26) in an inert solvent, such as, but not limited to, dichloromethane or dichloroethane, followed by treatment with bases, such as, but not limited to, potassium carbonate to provide the compounds of formula (27).

The compounds of formula (23) can be treated with carboxylic acids having the formula AC (O) OH (examples of such carboxylic acids include compounds of formula (7), (13), and the like) or their salts, and an agent of activation, optionally in the presence of 1-hydroxy-7-azabenzotriazole (HOAT), 1-hydroxybenzotriazole hydrate 15 (HOBT) or 3-hydroxy-1,2,3-benzotriazin-4 (3H) -one (HOOBT), and optionally in the presence of an inorganic base (for example, NaHCO3, Na2CO3, KHCO3, K2CO3, NaOH or KOH and the like) in an inert solvent (for example, 1: 1 ethyl acetate / water or isopropyl acetate / water or toluene / water or THF / water and the like) at about room temperature, or an organic amine base (for example, imidazole, 1-methylimidazole, 2-methylimidazole, 2isopropylimidazole, 4-methylimidazole, 4-nitroimidazole, pyridine, N, N- dimethylaminopyridine, 1,2,4-triazole, pyrrole, 3-methylpyrrole, triethylamine or N-methylmorpholine and the like) in an inert solvent (e.g., ac ethyl ethate, isopropyl acetate, THF, toluene, acetonitrile, DMF, dichloromethane and the like) at a temperature of about 0 ° C to about 50 ° C to provide the compounds of formula (24). Examples of the activating agent include, but are not limited to, 1,1'-carbonyldiimidazole (CDI), 1,3-dicyclohexylcarbodiimide (DCC), 1,3-diisopropylcarbodiimide, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDAC) ), DEPBT (3

25 (diethoxyphosphoryloxy) -1,2,3-benzotriazin-4 (3H) -one), PyBOP (benzotriazol-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate), and 1,3-di-tert-butylcarbodiimide.

Alternatively, a salt or an activated ester derivative of the acids of formula (7) or (13) (for example, the acid chloride, prepared by reacting the carboxylic acid with thionyl chloride in ethyl acetate or THF or chloride oxalyl in toluene / DMF) can be reacted with compounds of formula (23).

Similarly, the compounds of formula (27) can be treated with acids of formula AC (O) OH (for example, acids of formula (7), (13), and the like) or their corresponding salts to provide the compounds of formula (28).

The present invention will now be described together with certain preferred embodiments that are not intended to limit its scope. On the contrary, the present invention includes all alternatives, modifications and equivalents that may be included within the scope of the claims. Therefore, the following examples, which include preferred embodiments, will illustrate the preferred practice of the present invention, it being understood that the examples are intended to illustrate certain preferred embodiments and are presented to provide what is believed to be the most useful description and easily understandable of its procedures and conceptual aspects.

It will be understood that the term "purification", as used hereafter, unless otherwise indicated, means column chromatography using a silica gel column and eluting the column with a

45 solvent system as specified in the experimental details.

The compounds of the invention were named by ACD / ChemSketch version 4.01 1 (developed by Advanced Chemistry Development, Inc., Toronto, ON, Canada) or given names consistent with the ACD nomenclature.

Example 1

(1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2.2 methyl dimethylpropylcarbamate

55 Example 1A

(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoic acid

(L) -terc-leucine (10 g, 0.076 mol) was dissolved in 1,4-dioxane (40 ml) and treated with 2M NaOH (125 ml, 3.2 equivalents) followed by dropwise addition of methyl chloroformate (11.2 ml, 1.9 equivalents) at 25 ° C. The mixture was heated at 60 ° C for 22 h, cooled and extracted twice with dichloromethane. The aqueous layer was separated, cooled in an ice bath and acidified with 4N HCl (60 ml). The mixture was extracted three times with ethyl acetate, and the organic phase was separated, dried over sodium sulfate, filtered, and the solvents evaporated to give

65 14.1 g (98%) of the title compound.

Example 1B

Tert-Butyl 2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazinecarboxylate

5 Example 1A (8 g, 42.3 mmol) was dissolved in DMF (200 ml) and treated with EDAC (11.96 g, 1.48 equivalent) and HOBT (8.8 g, 1.54 equivalents) at 25 ° C. After stirring this mixture for 15 min, t-butyl carbazate (6.1 g, 1.1 equivalents) was added followed by N-methyl morpholine (8 ml, 1.72 equivalents) and stirring continued at 25 ° C for 16 h. The mixture was quenched with 1 N sodium bicarbonate and extracted twice with ethyl acetate. The solvents were evaporated, and the residue was purified using 30% ethyl acetate / hexanes to give 11.5 g (90%) of the title compound.

Example 1C

(1S) -1- (methyl hydrazinocarbonyl) -2,2-dimethylpropylcarbamate

Example 1B (11.5 g, 0.037 mol) was dissolved in THF (200 ml) and 4 N HCl (70 ml) at 60 ° C for 5 h. The solvents were evaporated to give 9.2 g (quant.) Of the title compound as the hydrochloride salt.

Example 1D

(1S) -2,2-Dimethyl-1 - ({(2E) -2- [4- (2-pyridinyl) benzylidene] hydrazino} carbonyl) propylcarbamate methyl

Example 1C (9.2 g, 0.045 mol) was dissolved in 2-propanol (90 ml) and treated with 4- (2-pyridyl) benzaldehyde (7 g, 1 equivalent) for 10 min before heating to 80 ºC for 4 h. The mixture was cooled, treated with

25 hexanes (90 ml), and the solids were filtered and partitioned between 1 N sodium bicarbonate and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, and the solvents evaporated to give 12.8 g (91%) of the title compound.

Example 1E

(1S) Methyl -2,2-dimethyl-1 - ({2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) propylcarbamate

Example 1D (6.4 g, 0.017 mol) was dissolved in methanol (64 ml) and treated with 10% Pd / C (0.64 g) and a hydrogen balloon at 25 ° C for 16 h. The catalyst was filtered, and the solvents evaporated. The solids were purified

Using 80% ethyl acetate / hexanes to give 10.7 g (83%) of the title compound.

Example 1F

(1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} -1- [4- (2

pyridinyl) benzyl] hydrazino} tert-butyl propylcarbamate

Example 1E (10.7 g, 0.029 mol) was dissolved in 2-propanol (30 ml) and hexanes (60 ml) and combined with (2S, 3S) -3N-tert-butoxycarbonylamino-1,2-epoxy- 4-phenylbutane (9.15 g, 1.2 equivalent) at 65 ° C for 2.5 days. The solvents were evaporated, and the mixture was triturated with 40% ethyl acetate / hexanes (200 ml) and heated to 60 ° C

45 for 4 min. The mixture was cooled and stirred at 25 ° C for 30 min before filtering the white solids. The mother liquor was evaporated and purified using 80% ethyl acetate / hexanes to give more grams with a total of 12 g (65%) of the title compound.

Example 1G

(1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2.2 methyl dimethylpropylcarbamate

Example 1F (12 g, 0.019 mol) was dissolved in THF (100 ml), treated with 4 N HCl (33 ml) and the mixture was heated to 60

55 ° C for 4 h. The solvents were evaporated, the mixture was made alkaline with saturated sodium bicarbonate (220 ml) and extracted twice with ethyl acetate. The organic layer was dried with Na2SO4 and the solvents evaporated to give 9.5 g (94%) of the title compound.

Example 2

(1S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate of methyl

Example 2A

65 (1S) -1 - {[(2E) -2- (4-methoxybenzylidene) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl p-anisaldehyde (0.34 g, 2.5 mmol) was dissolved in isopropanol (2 ml) and treated with Example 1C (0.1 g, 1 equivalent) at 80 ° C for 4 h. The mixture was partitioned between ethyl acetate and saturated sodium hydrosulfite, the organic layer was separated, washed with water, dried over sodium sulfate, filtered and the solvents evaporated to give 0.69 g (86%) of the compound. title, used directly without purification.

5 Example 2B

(1S) -1 - {[2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate

Example 2A (0.68 g, 2.1 mmol) was dissolved in dichloroethane (0.2 ml) and treated with sodium triacetoxy borohydride (0.86 g, 2 equivalent) and trifluoroacetic acid (25 μl, 1 , 5 equivalent) at 25 ° C for 4 h. The solvents were evaporated and the crude residue was purified using ethyl acetate: hexanes (2: 1) -ethyl acetate to give 0.4 g (57%) of the title compound.

Example 2C (1S, 2S) -1-benzyl-2-hydroxy-3- (1- (4-methoxybenzyl) -2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3dimethylbutanoyl} hydrazino) tert-butyl propylcarbamate

Example 2B (0.39 g, 1.23 mmol) was dissolved in isopropanol: hexanes (10 ml, 1: 1) and treated with (2S, 3S) -3-N-tert

20 butoxycarbonylamino-1,2-epoxy-4-phenylbutane (0.39 g, 1.1 equivalent) at 65 ° C for 2 days. The solvents were evaporated, and the crude residue was crystallized using ethyl acetate: hexanes (1: 1) to give 0.58 g (82%) of the title compound.

2D example

25 (1S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate of methyl

Example 2C (0.58 g, 0.99 mmol) was dissolved in THF (4.5 ml) and treated with 4 N HCl (1.5 ml) at 60 ° C for 3 h.

The solvents were evaporated and the crude residue was partitioned between dichloromethane and saturated sodium bicarbonate. The organic layer was separated, dried over sodium sulfate and the solvents evaporated to give 0.46 g (96%) of the crude title compound.

Example 3

35 (1S, 2S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-bromobenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate methyl

Example 3A

40 (3S, 4S) -3 - [(methoxycarbonyl) amino] -4-methylhexanoic acid

(L) -isoleucine (7.43 g, 57 mmol) was dissolved in dioxane (28 ml) and treated with 2 N sodium hydroxide (93.5 ml, 3.3 equivalents) and methyl chloroformate (8.75 ml , 2 equivalents) at 60 ° C for 16 h. The mixture was extracted with

45 dichloromethane (2 x). The mixture was made acidic with 4 N HCl, extracted with ethyl acetate (3 x), dried over sodium sulfate, filtered and the solvents evaporated to give 8.6 g (80%) of the title compound.

Example 3B

50 2 - {(2S, 3S) -2 - [(methoxycarbonyl) amino] -3-methylpentanoyl} tert-butyl hydrazinecarboxylate

Example 3A (0.54 g, 2.85 mmol) was dissolved in ethyl acetate (14 ml) and treated with EDAC (0.49 g, 1.1 equivalents), HOBT (0.42 g, 1, 1 equivalents), NMM (0.48 ml, 1.2 equivalents) and t-butyl carbazate (0.45 g, 1.2 equivalents) at 25 ° C for 16 h. The mixture was washed with saturated sodium bicarbonate, water and brine, dried

On sodium sulfate, it was filtered and the solvents evaporated. The crude residue was purified using 7% dichloromethane methanol / dichloromethane to give 0.77 g (89%) of the title compound.

Example 3C

60 (1S, 2S) -1- (methyl hydrazinocarbonyl) -2-methylbutylcarbamate

Example 3B (0.86 g, 2.85 mmol) was dissolved in 4 N HCl / dioxane (7.2 ml) at 25 ° C for 2 h. The mixture was quenched with saturated sodium bicarbonate and made basic with 1 N sodium hydroxide. The mixture was extracted with dichloromethane, dried over magnesium sulfate, filtered and the solvents evaporated to give 0.58 g (64%) of the compound of

65 title.

3D example

(1S, 2S) -1 - {[2- (4-bromobenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate

5 Example 3C (0.32 g, 1.58 mmol) was dissolved in isopropanol (8 ml) and treated with 4-bromobenzaldehyde (0.29 g, 1 equivalent) and magnesium sulfate (0.95 g, 5 equivalent) at 80 ° C for 3 h. The mixture was filtered, and the solvents were evaporated to give the crude imine which was dissolved in THF (8 ml) and treated with sodium cyanoborohydride (0.1 g, 1.05 equivalents) followed by toluenesulfonic acid (0 , 3 g, 1 equivalent) at 25 ° C for 16 h. The mixture was quenched with saturated sodium bicarbonate, the organic layer was dried over sodium sulfate, filtered and the solvents evaporated to give 0.36 g (61%) of the title compound.

Example 3E

(1S, 2S) -1-benzyl-3- (1- (4-bromobenzyl) -2 - {(2S, 3S) -2 - [(methoxycarbonyl) amino] -3-methylpentanoyl} hydrazino) -215 tert hydroxypropylcarbamate -butyl

Example 3D (0.36 g, 0.96 mmol) was dissolved in isopropanol (4.8 ml) and treated with (2S, 3S) -3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane ( 0.3 g, 1.2 equivalent) at 65 ° C for 1 h. The mixture was heated at 50 ° C for 2 days and cooled to room temperature. The solvents were evaporated and the crude residue was purified using 3% chloroform-methanol / chloroform to give 0.48 g (78%) of the title compound.

Example 3F

(1S, 2S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-bromobenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate 25 methyl

Example 3E (0.48 g, 0.755 mmol) was dissolved in THF (5 ml), treated with 2N HCl (3.8 ml) at 50 ° C for 16 h and cooled to room temperature. The solvents were concentrated, triturated with ethanol, and the solids filtered and dried to give 0.4 g (97%) of the title compound.

Example 4

2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] tert-butyl hydrazinecarboxylate

35 Example 4A

(2E) -2- [4- (2-Pyridinyl) benzylidene] tert-butyl hydrazinecarboxylate

4- (2-Pyridyl) benzaldehyde (15 g, 0.082 mol) was dissolved in ethanol (150 ml) and treated with t-butyl carbazate (10.3 g, 0.078 mol) at 80 ° C for 4 h. The mixture was combined with water (200 ml), the solids filtered, washed with water and dried in vacuo to give 22.5 g (92%) of the title compound.

Example 4B

45 2- [4- (2-Pyridinyl) benzyl] tert-butyl hydrazinecarboxylate

Example 4A (15 g, 0.05 mol) was dissolved in methanol (100 ml) and treated with 10% Pd / C (1.5 g) and a hydrogen balloon for 4 h. The catalyst was filtered, and the solvents evaporated to give 15 g (98%) of the title compound.

Example 4C

(1S) -1-benzyl-2-oxoethylcarbamate tert-butyl

(S) -N-Bocphenylalaninol (5 g, 0.019 mol) was dissolved in dichloromethane (150 ml) and triethylamine (8.3 ml, 3 equivalents) at

0 ° C and treated with a solution of sulfur pyridine-trioxide complex (9.5 g, 3 equivalents) in DMSO (30 ml) for several minutes. After 1 h at 0 ° C, the mixture was added to ice-water (200 ml). The dichloromethane was evaporated and the mixture was extracted with ether (100 ml, 4 x). The organic layer was washed with 10% citric acid, water, saturated sodium bicarbonate and brine, dried over sodium sulfate, and the solvents evaporated to give 5.3 g of the title compound.

Example 4D

(1S) -1-benzyl-2-propenylcarbamate tert-butyl

65 Triphenyl methylphosphonium bromide (13.1 g, 0.037 mol) was suspended in toluene (150 ml) and treated with 1 M potassium tert-butoxide in THF (28.8 ml, 0.8 equivalents) at 25 ° C for 16 h. This solution was added dropwise to a suspension of Example 4C in toluene (100 ml) at -78 ° C for 15 min. After 1.5 h, the mixture was heated to 25 ° C and partitioned between saturated ammonium chloride (100 ml) and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and the solvents evaporated. The oil was dissolved again in ether: hexanes (10 ml, 1: 1) and filtered to remove triphenylphosphine oxide. The filtrate was evaporated and the crude residue

5 was purified using ethyl acetate: hexanes (1: 6) to give 2.4 g (49%) of the title compound.

Example 4E

(1S) -1- (2-Oxyranyl) -2-phenyl-N- (trifluoromethyl) ethanamine

10 Example 4D (2.4 g, 9.7 mmol) was dissolved in 4 N HCl / dioxane (18 ml) at 25 ° C for 1 h. The solvents evaporated. This residue was dissolved in dichloromethane (15 ml) and treated with pyridine (8 ml, 10 equivalents) and trifluoroacetic anhydride (3 g, 1.5 equivalents) at 25 ° C for 1 h. The solvents were evaporated and the crude residue was partitioned between dichloromethane and saturated sodium bicarbonate. The organic layer was separated, dried over

15 sodium sulfate and the solvents were evaporated to give 2.63 g of crude olefin which was dissolved again in dichloromethane (50 ml) and treated with m-chloroperbenzoic acid (8.36 g, 1.5 equivalents, 70% ) at 0 ° C. The mixture was heated at 25 ° C for 16 h, diluted with ether (200 ml), washed with 10% sodium sulphite, saturated sodium bicarbonate and brine, dried over sodium sulfate, and the solvents evaporated. The crude residue was purified using 2% chloroform-methanol / chloroform to give 1.5 g (59%) of the title compound.

20 Example 4F

2 - {(2S, 3S) -2-hydroxy-4-phenyl-3 - [(trifluoromethyl) amino] butyl} -2- [4- (2-pyridinyl) benzyl] tert-butyl hydrazinecarboxylate

Example 4E (1.5 g, 5.8 mmol) was dissolved in isopropanol (22 ml) and treated with Example 4B (1.7 g, 1 equivalent) at 65 ° C for 16 h. The solvents were evaporated and the crude residue was purified using 0-50% chloroform in ethyl acetate to give 0.86 g (28%) of the title compound.

4G example

30 2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] tert-butyl hydrazinecarboxylate

Example 4F (0.2 g, 0.36 mmol) was dissolved in methanol (3.7 ml) and treated with 10% potassium carbonate (1.5 ml) at 60 ° C for 3 h. The mixture was diluted with chloroform, washed with brine, dried over magnesium sulfate,

35 filtered and the solvents evaporated. The crude residue was purified using chloroform-chloroform / 5% methanol / 0.2% ammonium hydroxide to give 0.17 g (100%) of the title compound.

Example 5

40 (1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl

Example 5A

1 - ({[2- (trimethylsilyl) ethoxy] carbonyl} oxy) -2,5-pyrrolidinedione

Trimethylsilyletanol (7.4 ml, 52 mmol) was dissolved in acetonitrile (260 ml) and treated with disuccinimoyl carbonate (20 g, 1.5 equivalents) and triethylamine (33 ml, 3 equivalents) at 25 ° C for 16 h . The solvents were evaporated, the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was triturated with ether to form a

Solid which was filtered and dried to give 11.12 g (82%) of the title compound.

Example 5B

2- (trimethylsilyl) ethyl hydrazinecarboxylate

Hydrazine hydrate (1.87 ml, 38 mmol) was dissolved in THF (16 ml) at 0 ° C and treated with Example 5A (2 g, 0.2 equivalent) in THF (7 ml) for 10 min. The mixture was heated at 25 ° C for 16 h and diluted with ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over sodium sulfate and the solvents evaporated to give 1.31 g (99%) of a crude oil which was dissolved again in ethanol (14 ml) and

60 was treated with benzaldehyde (0.72 ml, 1 equivalent) at 25 ° C for 2 days. The solvents were evaporated and the crude residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated. The crude oil was crystallized by treatment with ether / hexane and filtered to give 1.85 g (99%) of the title compound.

65 Example 5C

2- (Trimethylsilyl) ethyl 2-benzylhydrazinecarboxylate

5 Example 5B (1.69 g, 6.4 mmol) was dissolved in THF (25 ml) and treated with sodium cyanoborohydride (0.48 g, 1.2 equivalents) followed by the addition of a solution of toluenesulfonic acid (1.4 g, 1.2 equivalents) in THF (12 ml) at 25 ° C for 1 day. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated, washed with brine, dried over sodium sulfate, and the solvents evaporated. The crude residue was dissolved in THF: methanol (10 ml, 5: 1) and treated with 1 N sodium hydroxide (35 ml) at 0 ° C for 1 h. The mixture was extracted with ethyl acetate, the organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 1.74 g (100%) of the crude product.

Example 5D

2- (Trimethylsilyl) ethyl 2-benzyl-2 - {(2S, 3S) -3 - [(tert-butoxycarbonyl) amino] -2-hydroxy-4-phenylbutyl} hydrazinecarboxylate

Example 5C (1.7 g, 6.4 mmol) was dissolved in isopropanol (17 ml) and treated with (2S, 3S) -3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (1, 68 g, 1 equivalent) at 65 ° C for 16 h. The solvents were evaporated, and the crude residue was purified using 8% hexane-acetone / hexane to give 1.61 g (48%) of the title compound.

Example 5E

(1S, 2S) -1-benzyl-3- (1-benzylhydrazino) -2-tert-butyl hydroxypropylcarbamate

Example 5D (1.42 g, 2.68 mmol) was dissolved in THF (26 ml) and treated with 1 M tetrabutylammonium fluoride in THF (8.4 ml, 3 equivalents) at 25 ° C for 1 h followed 50 ° C for 3 h. The mixture was partitioned between chloroform and water, the organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 1.01 g (100%) of the title compound.

Example 5F

(1S, 2S) -1-Benzyl-3- (1-benzyl-2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazino) -2-tert-butyl hydroxypropylcarbamate

A 0.2 M solution of Example 5E (2 ml, 0.4 mmol) in THF was treated with Example 1A (79 mg, 1.1 equivalents), DEPBT (0.24 g, 2 equivalents) and triethylamine ( 0.22 ml, 4 equivalents) at 25 ° C for 16 h. The mixture was treated with 10% sodium carbonate and dichloromethane, the organic layer was separated, dried over sodium sulfate, filtered and the solvents evaporated.

Example 5G

(1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzylhydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl

A solution of Example 5F in THF (4 ml) was treated with 4 N HCl and stirred at 70 ° C for 3 h. The mixture was cooled to room temperature and quenched with saturated sodium bicarbonate and ethyl acetate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 83 mg (100%) of the title compound.

Example 6

(1S, 2S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzylhydrazino} carbonyl) -2-methylbutylcarbamate methyl

A solution of Example 5E (1.38 ml, 0.2 M solution in THF, 0.275 mmol) was treated with Example 3A (57 mg, 1.2 55 equivalents), DEPBT (99 mg, 1.2 equivalents) and triethylamine (92 μl, 2.4 equivalents) and stirred at 25 ° C for 4

h. The mixture was treated with 10% sodium carbonate (2 ml) and dichloromethane. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated. The crude residue was purified using ethyl acetate to give 79 mg (51%) of the crude product. This material was dissolved in THF (4 ml) and treated with 4 N HCl (2 ml) at 70 ° C for 3 h. The mixture was quenched with saturated sodium bicarbonate and ethyl acetate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 65 mg (100%) of the title compound.

Example 7A

65 2 - {(2S, 3S) -3 - [(tert-butoxycarbonyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] tert-butyl hydrazinecarboxylate A solution of Example 4B (0.84 g, 2.8 mmol) in isopropanol (9 ml) was treated with (2S, 3S) -3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (0.74 g, 1 equivalent), stirred at 65 ° C for 16 h and cooled to room temperature. The mixture was partitioned between water and dichloromethane. The organic layer was separated, dried over sodium sulfate, filtered and the solvents concentrated. Ether was added to precipitate the solid that was filtered to give 0.8 g

5 (57%) of the title compound.

Example 7B

(1S, 2S) -1-Benzyl-2-hydroxy-3- {1- [4- (2-pyridinyl) benzyl] hydrazino} tert-butyl propylcarbamate

A solution of Example 7A (0.6 g, 1.1 mmol) in THF (5.3 ml) was treated with 4 N HCl (1.9 ml), stirred at 60 ° C for 3 h and cooled to temperature ambient. The solvents were evaporated and the residue was azeotropically distilled with ethanol twice to give 0.6 g (100%) of the hydrochloride salt of the title compound. This salt was dissolved in THF (20 ml) and treated with sodium bicarbonate (0.43 g, 4 equivalents) in water (5 ml) and BoC2O (0.295

15 μl, 1 equivalent) at 25 ° C for 3 h. The solvents were evaporated, and the crude residue was partitioned between chloroform and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated. The crude residue was purified using 2% methanol / chloroform to give 0.357 g (72%) of the title compound.

20 Example 7C

(1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {(2S, 3S) -2 - [(methoxycarbonyl) amino] -3-methylpentanoyl} -1- [4- (2

pyridinyl) benzyl] hydrazino} tert-butyl propylcarbamate

A solution of Example 7B (0.36 g, 0.77 mmol) in dichloromethane (5 ml) was treated with O- (1,2-dihydro-2-oxo-1-pyridyl) -N, N, N 'tetrafluoroborate. , N'-tetramethyluronium (TPTU) (0.344 g, 1.5 equivalent), and diisopropylethyl amine (0.4 μl, 3 equivalents) at 0 ° C for 20 min. A solution of Example 3A (0.22 g, 1.5 equivalent) in dichloromethane (5 ml) was added at 0 ° C and the mixture was stirred at 25 ° C for 16 h. The mixture was washed with water, 10% sodium bicarbonate and brine, the organic layer was separated, dried over sodium sulfate, filtered and the solvents were

30 evaporated. The crude residue was purified using 1% methanol / chloroform to give 0.37 g (76%) of the title compound.

Example 7D

35 (1S, 2S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) - Methyl 2-methylbutylcarbamate

A solution of Example 7C (0.37 g, 0.59 mmol) in THF (4 ml) was treated with 4 N HCl (1 ml), stirred at 60 ° C for 3 h and cooled to room temperature. The solvents were evaporated, and the crude residue was partitioned between

40 ethyl acetate and 10% sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 0.28 g (89%) of the title compound.

Example 8

45 (2S) -N '- [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -5-oxo-N' - [4- (2-pyridinyl) benzyl] -2-pyrrolidinecarbohydrazide

(L) Pyroglutamic acid (14 mg, 0.11 mmol) was dissolved in THF (1.1 ml) and treated with Example 7B (50 mg, 1 equivalent), triethylamine (0.11 ml, 7 equivalents) and DEPBT (48 mg, 1.5 equivalents) at 25 ° C for 16 h. The mixture was partitioned between ethyl acetate and 10% potassium carbonate, the organic layer was separated, washed with

Brine, dried over magnesium sulfate, filtered and the solvents evaporated. The crude residue was purified using 0-10% methanol / chloroform to give 31 mg (48%) of the title compound. This material (28 mg, 0.049 mmol) was dissolved in dichloromethane: trifluoroacetic acid (0.6 ml, 1: 1) at 25 ° C for 2 h, and the solvents were evaporated to give 23 mg (100%) of the title compound in the form of the trifluoroacetic acid salt.

The compounds listed in Table 1, in which X4 represents the point of attachment to the core structure (A), were prepared by the procedures illustrated in Example 8, replacing the corresponding acids with (L) -acid pyroglutamic:

Table 1

Ex.

R4  Ex. R4

9

12

10

13

eleven

Example 14 5 (3R) -2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] 2-oxotetrahydro-3-furanyl hydrazinecarboxylate

Example 14A

1 - [({[(3R) -2-oxotetrahydro-3-furanyl] oxy} carbonyl) oxy] -2,5-pyrrolidinedione

10 (R) -alpha-hydroxybutyrolactone (8 μl, 0.11 mmol) was dissolved in acetonitrile (0.5 ml) and treated with triethylamine (45 μl, 1.5 equivalents) and disuccinimidyl carbonate (42 mg, 1 , 5 equivalents) at 25 ° C for 16 h. The solvents were evaporated, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was separated, washed with brine, dried over magnesium sulfate, filtered and evaporated.

15 Example 14B

(3R) -2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] 2-oxotetrahydro-3-furanyl hydrazinecarboxylate

A solution of Example 7B (50 mg, 0.11 mmol) in THF (1 ml) was treated with triethylamine (80 μl, 5 equivalents) and

Example 14A (26 mg, 1 equivalent), stirred at 50 ° C for 2 h and cooled to room temperature. The mixture was evaporated and purified using 20% chloroform / ethyl acetate to give 23 mg (35%) of the title compound. This material was dissolved in dichloromethane: trifluoroacetic acid (0.4 ml, 1: 1), stirred at 25 ° C for 1 h, and the solvents evaporated to give 23 mg (100%) of the title compound as trifluoroacetic acid salt.

25 Example 15

(3S) -2 - [(2S, 3R) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] 2-oxotetrahydro-3-furanyl hydrazinecarboxylate

Example 15 was prepared using the procedures of Examples 14A and 14B, substituting (R) -alphahydroxybutyrolactone for (S) -alpha-hydroxybutyrolactone.

Example 16

35 (3R) -2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] 4,4-dimethyl-2-oxotetrahydro-3 hydrazinecarboxylate -furanyl

Example 16 was prepared using the procedures of Examples 14A and 14B, substituting (R) -alphahydroxybutyrolactone for (R) -alpha-pantolactone.

Example 17

(3S) -2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] 4,4-dimethyl-2-oxotetrahydro-3- hydrazine carboxylate furanyl

5 Example 17 was prepared using the procedures of Examples 14A and 14B, substituting (R) -alphahydroxybutyrolactone for (S) -alpha-pantolactone.

Example 18

(1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzylhydrazino} carbonyl) -2-methylpropylcarbamate methyl

Example 18A

15 (2S) -�? Acid 2 - [(methoxycarbonyl) amino] -3-methylbutanoic acid

A solution of (L) -valine (7.43 g, 57 mmol) in dioxane (28 ml) was treated with 2 N sodium hydroxide (93.5 ml, 3.3 equivalents) and methyl chloroformate (8.75 ml , 2 equivalents), stirred at 60 ° C for 16 h and cooled to room temperature. The mixture was extracted with dichloromethane (2 x). The mixture was acidified with 4 N HCl, extracted with ethyl acetate (3 x), dried over sodium sulfate, filtered and the solvents evaporated to give 8.6 g (80%) of the title compound.

Example 18B

Methyl 25 (1S) -2-methyl-1 - ({2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) propylcarbamate

A solution of Example 4B (0.18 g, 0.6 mmol) in dichloromethane: trifluoroacetic acid (4 ml, 1: 1) was stirred at 25 ° C for 1 h and the solvents evaporated. This material was dissolved in THF (1 ml) and treated with diisopropylethyl amine (0.31 ml, 3 equivalents), DEPBT (0.36 g, 2 equivalents) and Example 18A (0.105 g, 1 equivalent) and stirred at 25 ° C for 3 h. The mixture was partitioned between dichloromethane and 10% sodium carbonate, the organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated. The crude residue was purified using 2% methanol / chloroform to give 0.1 g (47%) of the title compound.

Example 18C

35 (1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {(2S) -2 - [(methoxycarbonyl) amino] -3-methylbutanoyl} -1- [4- (2-pyridinyl) benzyl] hydrazino } tert-butyl propylcarbamate

A solution of Example 18B (0.1 g, 0.28 mmol) in hexane: isopropanol (6 ml, 1: 1) was treated with (2S, 3S) -3-N-tert-butoxycarbonylamino-1,2-epoxy-4 -phenylbutane (75 mg, 1 equivalent), stirred at 70 ° C for 2 days and cooled to room temperature. The solvents were evaporated and the crude residue was purified using 2% methanol / chloroform to give 0.11 g (63%) of the title compound.

Example 18D

45 (1S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2- methyl methyl propylcarbamate

A solution of Example 18C (0.11 g, 0.18 mmol) in THF (2 ml) was treated with 4 N HCl (0.3 ml), stirred at 60 ° C for 3 h and cooled to room temperature. The mixture was concentrated, neutralized with 10% sodium bicarbonate, extracted with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered and the solvents evaporated to give 92 mg (100%). of the title compound.

Example 19

55 (1S) -1 - [(2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2 - {[2- (5-methyl-3-isoxazolyl) -1.3 -thiazol-4-yl] methyl} hydrazino) carbonyl] methyl 2,2-dimethylpropylcarbamate

Example 19A

(1S, 2S) -1-benzyl-2-hydroxy-3- (2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazino) propyl tert-butyl carbamate

A solution of Example 5F (0.115 g, 0.2 mmol) in methanol (2 ml) was treated with Pd (OH) 2 (38 mg) and 4 N HCl (52 μl, 1

65 equivalent) and a hydrogen balloon at 25 ° C for 3.5 h. The solvents were evaporated, and the crude residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was separated, washed with brine,

dried over sodium sulfate, filtered and the solvents evaporated to give 90 mg (93%) of the title compound.

Example 19B

5 (1S, 2S) -1-benzyl-2-hydroxy-3- (2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} -1 - {[2- (5- methyl-3-isoxazolyl) -1,3thiazol-4-yl] methyl} hydrazino) tert-butyl propylcarbamate

A solution of Example 19A (0.4 g, 0.86 mmol) in dichloroethane (5.7 ml) was treated with acetic acid (99 μl, 2 equivalents), 2- (5-methyl-3-isoxazolyl) thiazole 4 -carboxaldehyde (0.199 g, 1.2 equivalents) and triacetoxy borohydride

10 sodium (0.545 g, 3 equivalents) and stirred at 25 ° C for 16 h. The mixture was diluted with dichloromethane and saturated sodium bicarbonate. The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered and the solvents evaporated. The crude residue was purified by HPLC reverse phase chromatography using water (0.1% trifluoroacetic acid): acetonitrile (95: 5) to acetonitrile (100%) to give 0.55 g (60%) of the title compound .

15 Example 19C

(1S) -1 - [(2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2 - {[2- (5-methyl-3-isoxazolyl) -1,3- thiazol-4-yl] methyl} hydrazino) carbonyl]

Methyl 2,2-dimethylpropylcarbamate

A solution of Example 19B (0.268 g, 0.42 mmol) in THF (2.1 ml) was treated with 4 N HCl (0.7 ml), stirred at 60 ° C for 3 h and cooled to room temperature. The solvents were evaporated to give 0.2 g (100%) of the trifluoroacetic acid salt of the title compound.

The compounds listed in Table 2, in which X3 represents the point of attachment to the core structure (B), were prepared by the procedures illustrated in Examples 19B and 19C, substituting 2- (5-methyl-3isoxazolyl) ) thiazole 4-carboxaldehyde by the corresponding aldehydes:

Table 2

Ex.

R3  Ex. R3

twenty

2. 3

twenty-one

24

22

25

Example 26

(1S, 2S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzylhydrazino} carbonyl) -2-methylbutylcarbamate 35 Example 26A

(1S, 2S) -1 - [(2-benzylhydrazino) carbonyl] -2-methylbutylcarbamate

A solution of Example 3A (3.32 g, 17.5 mmol) in THF (70 ml) was treated with benzylhydrazine di-HCl salt (3.42 g, 1 40 equivalent), diisopropylethyl amine (9.2 ml, 3 equivalent), EDAC (6.05 g, 1.8 equivalent) and HOBT (3.56 g, 1.5

equivalent) and stirred at 25 ° C for 16 h. The solvents were evaporated, and the crude residue was partitioned between chloroform and 10% sodium bicarbonate. The organic layer was separated, washed with 10% sodium bicarbonate and brine, dried over sodium sulfate, filtered and the solvents evaporated. The crude residue was purified using 1% methanol / chloroform to give 2.41 g (47%) of the title compound.

5 Example 26B

(1S, 2S) -1-benzyl-3- (1-benzyl-2 - {(2S, 3S) -2 - [(methoxycarbonyl) amino] -3-methylpentanoyl} hydrazino) -2

tert-butyl hydroxypropylcarbamate

A solution of Example 26A (2.41 g, 8.2 mmol) in isopropanol: hexane (42 ml, 1: 1) was treated with (2S, 3S) -3-N-tert-butoxycarbonylamino-1,2-epoxy-4 -phenylbutane (2.19 g, 1 equivalent), stirred at 65 ° C for 16 h and cooled to room temperature. The mixture was combined with brine and extracted three times with chloroform. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and the solvents were

15 evaporated. The crude residue was purified using 2% methanol / chloroform to give 4.57 g (100%) of the title compound.

Example 26C

(1S, 2S) -1 - ({2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2-benzylhydrazino} carbonyl) -2-methylbutylcarbamate methyl

A solution of Example 26B (4.57 g, 8.2 mmol) in THF (60 ml) was treated with 4 N HCl (14.4 ml), stirred at 60 ° C for 3 h and cooled to room temperature. The solvents were evaporated, and the crude residue was partitioned between ethyl acetate and 10% sodium bicarbonate. The organic layer was separated, washed with sodium bicarbonate at

10% and brine, dried over sodium sulfate, filtered and the solvents evaporated to give 3.41 g (89%) of the title compound.

Example 27

(1S, 2S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate methyl

Example 27A

35 (1S, 2S) -1-benzyl-2-hydroxy-3- (1- (4-methoxybenzyl) -2 - {(2S, 3S) -2 - [(methoxycarbonyl) amino] -3methylpentanoyl} hydrazino) propylcarbamate tert-butyl

A solution of Example 26B (1.2 g, 2.2 mmol) in methanol (7 ml) was treated with Pd (OH) 2 (0.24 g), 4 N HCl (0.54 ml) and stirred in a hydrogen balloon at 25 ° C for 16 h. The catalyst was filtered, washed with methanol, and the solvents evaporated to give 1 g (100%) of the crude product that was used directly in the next step. This material (0.5 g, 1.1 mmol) was dissolved in dichloroethane (4 ml) and treated with acetic acid (0.12 ml, 2 equivalents), sodium triacetoxyborohydride (0.57 g, 2.5 equivalents) and p-anisaldehyde (0.26 ml, 2 equivalents) at 25 ° C for 16 h. The mixture was quenched with 10% sodium bicarbonate and chloroform. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and the solvents evaporated. The raw waste is

Purified using 1% methanol / chloroform to give 0.38 g (60%) of the title compound.

Example 27B

(1S, 2S) -1 - {[2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methyl-butylcarbamate methyl

Example 27A (0.38 g, 0.6 mmol) was dissolved in THF (5 ml) treated with 4 N HCl (1.1 ml), stirred at 60 ° C for 3 h and cooled to room temperature. The solvents were evaporated, and the residue was triturated with ethanol, filtered and dried to give 0.29 g (100%) of the title compound.

55 Example 28

(2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoic acid

Example 28A

(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) acetaldehyde

To a solution of diethylacetal phthalimide (15 g) in tetrahydrofuran (THF) (30 ml) was added 10% aqueous HCl (18

65 ml) After heating at 75 ° C for 5 h, the solution was allowed to cool to room temperature, the ethyl acetate was separated and dried over magnesium sulfate (MgSO4). The solution was filtered and evaporated to provide 11.2 g of the title compound.

Example 28B

Tert-Butyl 5 (2S, 3S) -2 - {[2- (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl] amino} -3-methylpentanoate

To a solution of Example 28A (12.1 g) in methanol (20 ml) was added Lisoleucine tert-butyl ester hydrochloride (13.0 g, 58 mmol), sodium cyanoborohydride (7.3 g, 116 mmol) and acetic acid (2 ml). The resulting solution was stirred for 3 h at 25 ° C, the methanol was removed in vacuo, dichloromethane (500 ml) was added and the solution was washed

10 with aqueous NaHCO3 (2 x 300 ml). The organic layer was concentrated to give 12.9 g of the title compound.

Example 28C

Tert-Butyl (2S, 3S) -2 - [(2-aminoethyl) amino] -3-methylpentanoate

To a solution of Example 28B (12.9 g) in ethanol (400 ml) was added hydrazine hydrate (11.2 ml). Then, the solution was heated at 70 ° C for 2 h. After cooling to 25 ° C, the resulting solid was dissolved in a 1 N solution of NaOH (200 ml) and water (200 ml). Then, the solution was extracted with dichloromethane (3 x 200 ml), the organic extracts were combined, dried and evaporated to provide 6.8 g of the title compound.

20 Example 28D

Tert-Butyl (2S, 3S) -3-methyl-2 - [(2 - {[(6-methyl-2-pyridinyl) methyl] amino} ethyl) amino] pentanoate

6-Methyl-2-pyridinecarboxaldehyde (4.25 g) was dissolved in dichloromethane (80 ml), combined with Example 28C (8 g, 1 equivalent) and MgSO4 (15 g) and the mixture was stirred at 25 ° C for 2.5 h. The mixture was filtered, rinsed with dichloromethane, and the solvents evaporated. The residue was dissolved in methanol (80 ml) and treated with NaBH4 at 0 ° C for 0.5 h. The solvents were evaporated, and the residue was partitioned between saturated NaHCO3 and ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and the solvents evaporated.

30 to give 11 g of the title compound.

Example 28E

Tert-Butyl (2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoate

A solution of the product of Example 28D in DMF (60 ml) was treated with bis- (p-nitrophenyl) carbonate (12.6 g, 1.2 equivalents) at 50 ° C for 5 h. The solvents were evaporated, and the residue was partitioned between water and ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, the solvents were evaporated, and the residue was purified using ethyl acetate: hexanes (2: 1) to give 7.3 g (57%) of the compound of the Title.

40 Example 28F

(2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoic acid

A solution of the product of Example 28E (7.3 g) in dichloromethane (50 ml) and trifluoroacetic acid (50 ml) was stirred at 25 ° C for 3.5 h. The solvents were evaporated and the crude acid was used directly without purification.

The compounds listed in Table 3, in which X1 and X5 represent the points of attachment to the core structure (C), were prepared by the procedures illustrated in Examples 28A-28F, substituting 6-methyl-250 pyridinecarboxaldehyde for corresponding aldehydes, and substituting Lisoleucine tert-butyl ester hydrochloride for the corresponding amino acid esters:

Table 3

Ex.

R5 R1  Ex. R5 R1

29

30

Ex.

R5 R1  Ex. R5 R1

31

32

33

3. 4

35

36

37

38

39

40

41

42

43

44

Four. Five

46

47

48

49

fifty

51

52

53

54

55

56

Ex.

R5 R1  Ex. R5 R1

57

58

59

60

Example 61

(2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazol-4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoic acid

5 Example 61A

2 - {[(2-methyl-1,3-thiazol-4-yl) methyl] amino} ethanol 2-methyl-4- (chloromethyl) thiazole (2.24 g) was treated with ethanolamine (11.6 ml, 10 equivalents) in dichloromethane at 25 ° C for 16 h. The solvent was evaporated and the residue was partitioned between ethyl acetate and brine. The organic layer was separated and extracted with ethyl acetate (5 x). The organic layers are

10 combined, washed with brine, dried over Na2SO4, and the solvents evaporated to give 2.4 g (85%) of the title compound.

Example 61B

Tert-Butyl 2-hydroxyethyl [(2-methyl-1,3-thiazol-4-yl) methyl] carbamate

The product of Example 61A (2.4 g) was treated with di-t-butyl dicarbonate (2.85 g, 1 equivalent) in tetrahydrofuran / 1 M NaHCO3 (2: 1) and stirred at 25 ° C for 16 h . The solvents were evaporated, the residue was acidified with 10% citric acid and extracted with ethyl acetate (3 x). The combined organic layer was washed with

Brine, dried over Na2SO4, filtered and evaporated. The crude product was purified using 1% methanol / dichloromethane to give 1.91 g (52%) of the title compound.

Example 61C

25 (2S) -3-methyl-2 - [(2 - {[(2-methyl-1,3-thiazol-4-yl) methyl] amino} ethyl) amino] methyl butanoate

A solution of the product of Example 61B (2.26 g) in dichloromethane (20 ml) was treated with oxalyl chloride (5.4 ml, 1.5 equivalents) at -78 ° C and stirred for 15 min. DMSO (1.02 ml, 2 equivalents) was added dropwise at -78 ° C, stirred for 15 min and quenched with triethylamine (4 ml, 4 equivalents) as the mixture was heated to 0 ° C. The mixture was quenched with 20% KH2PO4 and partitioned between dichloromethane and water. The organic layer was washed with brine, dried over Na2SO4, and the solvents evaporated. To this crude product was added methanol / water (7: 2), (L) -valine methyl ester (1.21 g, 1 equivalent), sodium acetate trihydrate (1.96 g, 2 equivalents) and added in NaCNBH3 portions (0.95 g, 2 equivalents) for 30 min. After stirring for 1 hour, the mixture was partitioned between saturated NaHCO3 and extracted with ethyl acetate (2 x). The combined organic layer is

35 washed with brine, dried with Na2SO4, filtered and evaporated. The residue was treated with dichloromethane / trifluoroacetic acid (10 ml, 1: 1), stirred at 25 ° C for 2 h and concentrated to give the title compound isolated as the trifluoroacetic acid salt.

Example 61D

40 (2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazol-4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoic acid

A solution of the product of Example 61C (5.4 g) in tetrahydrofuran (80 ml) was treated with carbonyldiimidazole (6.1 g, 2 equivalents) at 25 ° C for 2 h. The mixture was quenched with 10% citric acid, the organic layer was separated,

45 washed with water and brine, dried over Na2SO4 and the solvents evaporated. A solution of the residue (3.3 g) in dioxane (20 ml) was treated with 1 M LiOH (20 ml) at 25 ° C for 2 h. The solvents were evaporated, the residue was acidified with 10% HCl, extracted with dichloromethane / 2-propanol (3: 1), the organic layer was separated, dried over Na2SO4, filtered and the solvents evaporated to give 1 , 5 g of the title compound.

The compounds listed in Table 4, in which X1 and X5 represent the points of attachment to the core structure (C), were prepared by the procedures illustrated in Examples 61A-61D, substituting 6-methyl-4 (chloromethyl ) thiazole with the corresponding halides, and substituting L-valine methyl ester for the corresponding amino acid esters:

Table 4

Example

Ex. R5 R1  Example Ex. R5 R1

365038

62 428059 63

Example 64

5 (2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2-yl) methyl] -2-oxo-1-imidazolidinyl} butanoic acid

Example 64A

2,2-dimethoxy-N - [(1-methyl-1 H -benzimidazol-2-yl) methyl] ethanamine

A solution of 1-methyl-2-formylbenzimidazole (1 g) in methanol (27 ml) and acetic acid (0.54 ml) was treated with diethyl acetal aminoacetaldehyde (0.9 g, 1 equivalent) and NaCNBH3 (0.85 g, 2 equivalents) at 25 ° C and stirred for 1 hour. The mixture was partitioned between water and ethyl acetate. The organic layer was separated, washed sequentially with saturated NaHCO3 and brine and concentrated. The residue was purified by eluting with methanol at

15 8% / dichloromethane to give 1.2 g (64%) of the title compound.

Example 64B

9H-fluoren-9-ylmethyl 2,2-dimethoxyethyl [(1-methyl-1H-benzimidazol-2-yl) methyl] carbamate

A solution of the product of Example 64A (1.2 g) in dichloromethane (30 ml) was treated with 9-fluorenylmethyl succinimide (1.6 g, 1.05 equiv.) At 0 ° C for 16 hours. The mixture was partitioned between water and ethyl acetate. The organic layer was separated, washed sequentially with 10% NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by eluting with ethyl acetate: dichloromethane (1: 1) to give 1.83 g (84%) of the compound of

25 title

Example 64C

9H-fluoren-9-ylmethyl (1-methyl-1H-benzimidazol-2-yl) methyl (2-oxoethyl) carbamate

A solution of the product of Example 64B (0.2 g) in tetrahydrofuran (0.2 ml) was treated with 30% HCl (0.2 ml), stirred at 75 ° C for 6 hours, cooled to 25 ° C and concentrated. The residue was partitioned between 10% NaHCO3 and ethyl acetate, the organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated to give the title compound (175 mg).

35 Example 64D

(2S) -2 - [(2 - {[(9H-fluoren-9-ylmethoxy) carbonyl] [(1-methyl-1H-benzimidazol-2-yl) methyl] amino} ethyl) amino] -3,3- methyl dimethylbutanoate

A solution of the product of Example 64C (0.178 g) and (L) -methyl t-leuccinate hydrochloride (76.1 mg, 1 equivalent) in methanol (1.7 ml) and acetic acid (17 μl) was treated with NaCNBH3 (54 mg, 2 equivalents) at 25 ° C for 3.5 hours. The mixture was partitioned between water and ethyl acetate. The organic layer was separated and washed with 1 N NaHCO3 and brine and concentrated. The residue was purified by ethyl acetate: dichloromethane (3: 1) to give 0.19 g (83%) of the

45 title compound.

Example 64E

(2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2-yl) methyl] -2-oxo-1-imidazolidinyl} methyl butanoate

A solution of the product of Example 64D (0.19 g) in N, N-dimethylformamide (3.5 ml) was treated with diethyl amine (0.35 ml), stirred at 25 ° C for 1.5 hours and He concentrated. A solution of the residue in dichloroethane (7 ml) was treated with bis- (p-nitrophenyl) carbonate (0.128 g, 1.2 equiv.), Stirred at 60 ° C for 16 hours and concentrated. The residue was purified by ethyl acetate: dichloromethane (3: 2) to give 80 mg (64%) of the title compound.

55 Example 64F

(2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2-yl) methyl] -2-oxo-1-imidazolidinyl} butanoic acid

A solution of the product of Example 64E (37 mg) in tetrahydrofuran (0.26 ml) and water (0.13 ml) was treated with LiOH (6.1 mg, 1.4 equivalents), stirred at 25 ° C for 16 hours, it was quenched with 1 N HCl (0.15 ml) at 0 ° C, and the solvents were evaporated to give the title compound, which will be used without further purification.

The compounds listed in Table 5, in which X1 and X5 respectively represent the binding points to the core structure (C), were prepared by the procedures illustrated in Examples 64A-64F, substituting for 1-methyl-2 -formylbenzimidazole corresponding, and substituting (L) -methyl-t-leuccinate for the corresponding amino acid esters.

Table 5

Ex.

R5 R1  Ex. R5 R1

65

66

67

68

69

10 Example 70

(1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate

15 methyl

Example 28 (40 mg) is combined with HOBT (23 mg, 1.5 equivalents) and EDAC (32 mg, 1.5 equivalents) in DMF (2 ml) and stirred for 1 hour at 25 ° C. To this mixture are added N-methylmorpholine (40 μl, 3 equivalents) and Example 1 (65 mg, 1.1 equivalents). The mixture is stirred for 16 h, evaporated and purified using methanol at

20 2% / CHCl3 to give 78 mg (86%) of the title compound. 1 H NMR (300 MHz, CDCl 3), δ ppm 0.78 (d, J = 7.72 Hz, 12 H), 0.85 (m, 3 H), 1.03 (m, 1 H), 1, 40 (m, 1 H), 1.91 (s, 1 H), 2.54 (s, 3 H), 2.61 (dd, J = 12.32, 3.86 Hz, 1 H), 2 , 81 (dd, J = 12.69, 10.11 Hz, 1 H), 2.92 (t, J = 8.09 Hz, 3 H), 3.11 (m, J = 4.04 Hz, 1 H), 3.17 (m, 3 H), 3.59 (s, 3 H), 3.64 (m, 2 H), 3.91 (m, 1 H), 3.97 (d, J = 6.62 Hz, 1 H), 4.07 (m, 1 H), 4.48 (s, 2 H), 4.79 (s, 1 H), 5.26 (d, J = 8 , 82 Hz, 1 H), 6.59 (d, J = 9.19 Hz, 1 H), 7.06 (dd, J = 12.13, 7.35 Hz, 2 H), 7.19 ( m, 6 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.54 (t, J =

25 7.72 Hz, 1 H), 7.74 (m, 2 H), 7.94 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 HOUR).

The compounds listed in Table 6, in which X1, X3, X4, and X5 respectively represent the points of attachment to the core structure (E), were prepared by the procedure of Example 70 (Method A), coupling the corresponding acids (Examples 28-69) having the formula (C), with the corresponding amines (Examples 1

27 27) having the formula (D); or by the procedure illustrated in Example 192 (Method D), replacing Example 191D with the corresponding amines (Examples 1-27), and replacing Example 18A with the corresponding amino acid esters (prepared from the corresponding amino acids using the procedure of Example 18A):

Table 6

Ex.

Method R5 R1 R3 R4

71

TO

72

TO

73

TO

74

TO

75

TO

76

TO

77

TO

78

TO

79

TO

80

D

81

D

82

D

Ex.

Method R5 R1 R3 R4

83

TO

84

TO

85

D

86

D

87

D

88

TO

89

D

90

D

91

TO

92

TO

93

TO

94

TO

Ex.

Method R5 R1 R3 R4

95

D

96

TO

97

D

98

TO

99

D

100

D

101

TO

102

D

103

D

104

TO

105

D

106

D

Ex.

Method R5 R1 R3 R4

107

D

108

D

109

D

110

TO

111

TO

112

TO

113

TO

114

TO

115

TO

116

TO

117

TO

118

D

Ex.

Method R5 R1 R3 R4

119

D

120

D

121

D

122

TO

123

TO

124

TO

125

TO

126

D

127

TO

128

D

129

D

130

D

Ex.

Method R5 R1 R3 R4

131

D

132

D

133

D

134

D

135

TO

136

TO

137

TO

138

TO

139

TO

140

TO

141

TO

Ex.

Method R5 R1 R3 R4

142

TO

143

TO

144

TO

145

D

146

D

147

D

148

D

149

D

150

D

151

D

152

D

153

D

Ex.

Method R5 R1 R3 R4

154

D

155

D

156

D

157

D

158

D

159

D

160

D

161

TO

162

TO

163

TO

164

TO

Ex.

Method R5 R1 R3 R4

165

D

166

TO

167

D

168

TO

169

TO

170

TO

171

TO

172

D

173

TO

174

TO

175

D

176

TO

Ex.

Method R5 R1 R3 R4

177

TO

178

D

179

TO

180

TO

181

TO

182

TO

183

TO

184

TO

185

TO

186

TO

187

TO

188

TO

Ex.

Method R5 R1 R3 R4

189

TO

190

D

Example 191

(1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -35 methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl

Example 191A

2 - {(2S, 3S) -3 - [(tert-butoxycarbonyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] tert-10-butyl hydrazinecarboxylate

(2S, 3S) -3-N-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutane (3 g, 0.011 mol) in isopropanol (50 ml) was combined with Example 4B (3.41 g, 1 equivalent ) and stirred at 85 ° C for 16 h. The mixture was cooled to room temperature, evaporated and partitioned between CHCl3 and brine. The organic layer was dried over sodium sulfate, filtered and

15 was evaporated to give an oil that was crystallized by trituration with diethyl ether, filtered and dried in vacuo to give 2.27 g (35%) of the title compound.

Example 191B

20 (2S, 3S) -3-amino-4-phenyl-1- {1- [4- (2-pyridinyl) benzyl] hydrazino} -2-butanol

Example 191A (2.27 g, 0.004 mol) was dissolved in THF (28 ml), treated with 4 N HCl (7.1 ml, 7 equivalents), heated at 60 ° C for 3 h and cooled to room temperature . The mixture was evaporated and azeotropically distilled twice in ethanol (30 ml), and the residue was dissolved in THF (32 ml) and treated with a solution of NaHCO3 (1.36 g,

25 4 equivalents) in water (8 ml). The mixture was stirred vigorously for 3 h at 25 ° C. The solvents were evaporated and the concentrate was partitioned between CHCl3 and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified using 1% methanol / CHCl3 to give 1.14 g (61%) of the title compound.

30 Example 191C

9H-fluoren-9-ylmethyl 2 - [(2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate

Example 191B (0.25 g, 0.69 mmol) was dissolved in THF (3 ml), combined with Fmoc-Osu (0.2 g, 1.1 equivalents) 35 and DCC (0.13 g, 1 , 2 equivalents) and the mixture was stirred at 25 ° C for 16 h. The mixture was filtered, evaporated and the residue was purified using 1% methanol / CHCl3 to give 0.21 g (57%) of the title compound.

Example 191D

40 (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -2- (3- { [2- (methoxymethyl) -1,3-thiazol-4yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanamide

Example 191C (0.21 g, 0.36 mmol) was dissolved in THF (2 ml), combined with 4 N HCl (0.5 ml, 7 equivalents) and heated at 60 ° C for 3 h. The solvents were evaporated, and the residue was azeotropically distilled twice with ethanol (20 ml). The residue was dissolved in THF (2 ml) and treated with Example 29 (105 mg, 1 equivalent), DEPBT (184 mg, 2 equivalents) and DIPEA (160 μl, 3 equivalents). The mixture was stirred at 25 ° C for 2 h. This mixture was treated with 10% Na2CO3 (10 ml) at 25 ° C for 20 min and extracted with dichloromethane. The extracts were combined, washed with 10% Na2CO3 and brine, and dried over sodium sulfate, filtered and evaporated. The crude residue was dissolved in THF (2 ml) and diethylamine (95 μl, 3 equivalents) and stirred at 25 ° C for 16 h. The

50 solvents were evaporated and the residue was purified using 2% methanol / CHCl3 to give 80 mg (38%) of the title compound.

Example 191E

(1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl

5 Example 191D (26 mg, 0.037 mmol) was dissolved dichloromethane (1 ml) and treated with tetrafluoroborate O- (1,2-dihydro-2-oxo-1-pyridyl) -N, N, N ', N'-tetramethyluronium (TPTU) (34 mg, 3 equivalents), N, N-di-isopropylethyl-amine (40 μl, 6 equivalents) followed by Example 1A (22 mg, 3 equivalents) at 0 ° C for 0.5 h and then at 25 ° C for 16 h. The solvents were evaporated, and the residue was purified using 2% methanol / CHCl3 to give 9 mg (28%) of the

10 title compound.

Example 192

(1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3

Methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate methyl Example 191D (20 mg, 0.029 mmol) was dissolved in THF (1 ml ) and treated with DEPBT (17.5 mg, 2 equivalents), Example 18A (5.1 mg, 1 equivalent) and diisopropylethyl amine (15.3 μl, 3 equivalents) at 25 ° C for 16 h. The mixture was combined with 10% sodium bicarbonate and dichloromethane. The organic layer was separated, washed with 10% sodium bicarbonate and brine, dried over sodium sulfate, filtered and the solvents evaporated. Raw waste

20 was purified using 1% methanol / chloroform to give 13.6 mg (35%) of the title compound. 1 H NMR (300 MHz, CDCl 3) δ ppm 0.70 (m, 6 H), 0.79 (d, J = 6.62 Hz, 3 H), 0.84 (m, 3 H), 0.99 (s, 1 H), 1.39 (d, J = 25.00 Hz, 1 H), 1.85 (dd, J = 13.79, 7.17 Hz, 1 H), 2.62 (s , 1 H), 2.82 (m, 1 H), 2.94 (m, 5 H), 3.12 (m, 1 H), 3.21 (m, 3 H), 3.48 (m , 3 H), 3.60 (s, 3 H), 3.66 (dd, J = 8.82, 6.99 Hz, 1 H), 3.89 (m, 1 H), 3.97 ( d, J = 19.85 Hz, 1 H), 4.05 (s, 1 H), 4.48 (s, 2 H), 4.69 (s, 2 H), 5.06 (d, J = 8.46 Hz, 1 H), 6.57 (d, J = 8.09 Hz, 1 H), 6.70 (s, 1 H), 7.18 (m, 7 H), 7.41 (d, J = 8.46 Hz, 2

25 H), 7.73 (m, 2 H), 7.94 (d, J = 8.46 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H).

The compounds listed in Table 7, in which X4 represents the point of attachment to the core structure (F), were prepared by the procedure illustrated by Example 192, replacing Example 18A with acids

corresponding:

Table 7

Ex. Nº

R4  Ex. Nº R4

193

194

195

196

197

Example 198

35 (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole -4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 4-phenylbutyl-2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl Example 198A

40 2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazol-4-yl) methyl] - 2-oxo-1-imidazolidinyl} butanoyl) amino] -4phenylbutyl} -2- [4- (2-pyridinyl) benzyl] tert-butyl hydrazinecarboxylate

Example 61 (64 mg, 0.22 mmol) was dissolved in THF (3 ml) and DMF (0.5 ml) and treated with HOBT (44 mg, 1.5 equivalents), EDAC (75 mg, 1, 8 equivalent) and N, N-diisopropylethylamine (DIPEA) (38 μl, 1 equivalent) followed by Example 4G (100 mg, 1 equivalent). The mixture was stirred at 25 ° C for 16 h. The solvents were evaporated and partitioned between ethyl acetate and saturated NaHCO3. The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated. The residue was purified using 2% methanol / CHCl3 to give 120 mg (75%) of the title compound.

Example 198B

(2S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3- [(2-methyl-1,3-thiazol-4-yl) methyl] 2-oxo-1-imidazolidinyl} butanamide

Example 198A (120 mg, 0.16 mmol) was dissolved in THF (1 ml) and 4 N HCl (0.3 ml) and the mixture was heated at 60 ° C for 3 h. The mixture was cooled to room temperature and the solvents evaporated. The residue was azeotropically distilled twice with ethanol (5 ml) and the title compound was used directly in the next step.

Example 198C

(1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole- 4-yl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] 4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl

Example 198B (46 mg, 1.5 equivalent) was dissolved in dichloromethane (3 ml) and treated with O (1,2-dihydro-2-oxo-1-pyridyl) -N, N, N ', tetrafluoroborate. N'-tetramethyluronium (TPTU) (72 mg, 1.5 equivalents) at 0 ° C followed by DIPEA (85 μl, 3 equivalents). The mixture was stirred for 20 min, combined with a solution of Example 1A, DIPEA (85 μl, 3 equivalents) in dichloromethane (2 ml) and stirred at 25 ° C for 16 hours. The solvents were evaporated and partitioned between CHCl3 and brine. The organic layer was dried over sodium sulfate, and the solvents evaporated. The residue was purified using 2% methanol / CHCl3 to give 38 mg (29%) of the title compound.

Example 199

(1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate tert-butyl

Example 199A

(2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- [[ 2-oxo-3- (4-quinolinyl-methyl) 1-imidazolidinyl] pentanamide

Example 75 (185 mg) was dissolved in THF (5 ml) and 4 N HCl (1.1 ml, 20 equivalents), heated at 60 ° C for 2 h and cooled to room temperature. The solvents were evaporated and the residue was azeotropically distilled twice in ethanol (10 ml) to give 164 mg of the title compound.

Example 199B

(1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate tert-butyl

Example 199A (164 mg) was dissolved in THF: DMF (2.2 ml, 10: 1) together with DEPBT (144 mg, 2 equivalents), TEA (230 μl, 7 equivalents) followed by Example 1A (61 mg, 1.1 equivalents). The mixture was stirred at 25 ° C for 4 h. The mixture was partitioned between ethyl acetate and 10% NaHCO3 and stirred vigorously for 30 min. The organic layer was separated, and the aqueous layer was extracted again with ethyl acetate. The organic layer was combined, washed with brine, dried over magnesium sulfate and evaporated. The residue was purified using chloroform: methanol

(98: 2) to give 156 mg (72%) of the title compound. 1 H NMR (300 MHz, CDCl 3) δ ppm 0.75 (m, 3 H), 0.82 (s, 9 H), 0.93 (m, 3 H), 1.33 (d, J = 5, 52 Hz, 1 H), 1.43 (m, 9 H), 1.89 (s, 1 H), 2.85 (m, 8 H), 3.57 (m, 1 H), 3.61 (s, 1 H), 3.91 (d, J = 11.03 Hz, 1 H), 4.00 (m, 2 H), 4.13 (d, J = 8.46 Hz, 1 H) , 4.25 (dd, J = 15.44, 6.99 Hz, 1 H), 4.80 (m, 2 H), 5.09 (d, J = 9.19 Hz, 1 H), 6 , 48 (d, J = 9.56 Hz, 1 H), 6.56 (s, 1 H), 7.05 (m, 3 H), 7.20 (m, 2 H), 7.35 ( m, 1 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.74 (m, 4 H), 7.95 (d, J = 8.46 Hz, 2 H), 7.95 (m, 1 H), 8.14 (d, J = 7.72 Hz, 1 H), 8.21 (d, J = 7.35 Hz, 1 H), 8.68 (d, J = 4.41 Hz, 1 H), 8.88 (d, J = 4.41 Hz, 1 H).

The compounds listed in Table 8, in which X4 represents the point of attachment to the core structure (G), were prepared by coupling the corresponding acids (Examples 28-69) with the corresponding amine (Example 199A), using the Procedure of Example 199B:

Table 8

Ex. Nº

R4  Ex. Nº R4

200

201

202

203

204

205

206

207

208

Example 209 5 (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4- quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate ethyl

Example 209A

10 (2S, 3S) -N - ((1S, 2S) -3- {2 - [(2S) -2-amino-3,3-dimethylbutanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino } -1-Benzyl-2-hydroxy-propyl) 3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide

Example 199B (150 mg, 0.17 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (1 ml) and stirred at 25 ° C for 1 h. The solvents were evaporated and the residue was partitioned between ethyl acetate and saturated NaHCO3, the organic layer was washed with brine, dried over MgSO4, filtered and evaporated to give the title compound, used directly in the next step.

Example 209B

20 (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl)) -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate ethyl

Example 209A (20 mg, 0.025 mmol) was dissolved in dichloromethane (0.3 ml) and treated with trifluoroacetic acid (8 μl, 2.2 equivalents) and ethyl chloroformate (3 μl, 1.1 equivalents) at 25 ºC for 16 hours. The solvents were evaporated, and the crude residue was purified using ethyl acetate: methanol (9: 1) with 0.2% ammonium hydroxide to give 9.2 mg (42%) of the title compound.

Example 210

(2S, 3S) -N - ((1S, 2S) -3- {2 - [(2S) -2- (acetylamino) -3,3-dimethylbutanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} -1-benzyl-2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide

5 Example 209A (20 mg, 0.025 mmol) was dissolved in dichloromethane (0.3 ml) and treated with trifluoroacetic acid (8 μl, 2.2 equivalents) and acetic anhydride (3 μl, 1.1 equivalents) at 25 ºC for 16 hours. The solvents were evaporated and the residue was purified by preparative TLC using 0.5 mm silica gel plates and CHCl3: methanol: NH4OH (90: 9.8: 0.2) to give 3.5 mg (17%) of the title compound.

10 Example 211

(1S, 2S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) ) -1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (3-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl

Example 79 (22 mg, 0.025 mmol) was dissolved in toluene (0.2 ml) and treated with tetrakis (triphenylphosphine) -palladium (0) (3 mg, 10% by mol, 0.1 equivalent) followed by 2M Na2CO3 (26 μl, 2 equivalents). The mixture was stirred at 25 ° C for 10 min and a solution of 3-pyridine boronic acid (6.3 mg, 2 equivalents) in ethanol (0.2 ml) was added. The mixture was heated in a microwave (150 ° C, 30 min.). The mixture was cooled to room temperature, diluted with

20 dichloromethane and filtered. The solvents were evaporated and the residue was purified by HPLC reverse phase chromatography using water (0.1% trifluoroacetic acid): acetonitrile (95: 5) to acetonitrile (100%) to give 15 mg (68%) of the compound Title. 1 H NMR (300 MHz, DMSO-d6) δ ppm 0.51 (d, J = 6.62 Hz, 3 H), 0.65 (m, 6 H), 0.77 (t, J = 7.17 Hz, 3 H), 1.00 (m, 3 H), 1.21 (d, J = 12.50 Hz, 3 H), 1.50 (m, 1 H), 1.78 (s, 1 H), 2.68 (m, 4 H), 3.06 (m, 3 H), 3.48 (d, J = 11.03 Hz, 3 H), 3.63 (d, J = 7, 72 Hz, 2 H), 3.98 (m, 2 H), 4.46 (s, 4 H), 4.87 (s, 2 H), 7.08 (m, 5 H), 7.52 (m, 3 H),

25 7.69 (m, J = 8.46 Hz, 3 H), 7.87 (t, J = 6.99 Hz, 1 H), 8.11 (d, J = 8.09 Hz, 1 H ), 8.29 (d, J = 7.72 Hz, 1 H), 8.37 (d, J = 7.72 Hz, 1 H), 8.66 (d, J = 5.15 Hz, 1 H), 8.99 (m, 2 H), 9.12 (s, 1 H).

The compounds listed in Table 9, in which X3a represents the point of attachment to the core structure (H), were prepared by the procedure illustrated in Example 211, coupling Example 79 with the boronic acids available in the market:

Table 9

Ex. Nº

R3a  Ex. Nº R3a

212

213

214

Example 215

35 (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) ) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

Example 84 (0.26 g, 0.34 mmol) was dissolved in trifluoroacetic acid: dichloromethane (3: 1) (10 ml) at 50 ° C for 2

40 h The solvents were evaporated, and the mixture was partitioned between saturated NaHCO3 and dichloromethane. The organic layer was separated, dried over sodium sulfate, evaporated, and the residue was purified using 5% methanol / CHCl3 to give 140 mg (64%) of the title compound.

Example 216

(1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- pyridinyl) ethyl] -2-oxo-1

methyl imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate

5 Example 215 (60 mg, 0.091 mmol) was dissolved in 1,2-dichloroethane (1 ml) and treated with isovaleraldehyde (10 mg, 1.2 equivalents) and acetic acid (15 μl, 3 equivalents) followed by triacetoxy sodium borohydride (60 mg, 3 equivalents) at 25 ° C for 16 h. The mixture was partitioned between saturated NaHCO3 and dichloromethane, the organic layer was separated, dried over sodium sulfate, filtered and the solvents evaporated. The residue was purified using

10% methanol / CHCl3 to give 36 mg (55%) of the title compound. 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (d, J = 6.25 Hz, 6 H), 0.87 (m, 6 H), 1.00 (s, 9 H), 1.07 (m, 1 H), 1.34 (m, 2 H), 1.45 (m, 1 H), 1.55 (m, 1 H), 1.94 (d, J = 11.03 Hz, 1 H), 2.54 (s, 3 H), 2.65 (d, J = 9.19 Hz, 1 H), 2.71 (m, 3 H), 2.93 (d, J = 7 , 72 Hz, 2 H), 3.07 (m, 1 H), 3.17 (m, 4 H), 3.58 (s, 3 H), 3.77 (d, J = 9.56 Hz , 1 H), 3.96 (m, J = 11.03 Hz, 2 H), 4.48 (m, 2 H), 5.35 (d, J = 9.56 Hz, 1 H), 6 , 74 (d, J = 8.46 Hz, 1 H), 6.88 (d, J = 18.02 Hz, 1 H), 7.06 (dd, J = 10.85, 7.54 Hz, 2 H), 7.15 (m, 5 H), 7.55 (t, J

15 = 7.72 Hz, 1 H).

The compounds listed in Table 10, in which X3 represents the point of attachment to the core structure (J), were prepared by the procedure illustrated in Example 216, substituting isovaleraldehyde for the commercially available aldehydes:

20 Table 10

Ex. Nº

R3  Ex. Nº R3

217

218

219

220

221

222

223

224

225

226

227

228

229

230

Ex. Nº

R3  Ex. Nº R3

231

232

233

2. 3. 4

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

Ex. Nº

R3  Ex. Nº R3

257

258

259

260

261

262

263

264

265

266

267

268

269

Example 270

2- (4-pyridinyl) -1,3-thiazol-4-carbaldehyde 5 Example 270A

Ethyl 2- (4-pyridinyl) -1,3-thiazol-4-carboxylate

A suspension of iso-thionicotinamide (5 g, 36.2 mmol) was dissolved in ethanol (90 ml) and treated with ethyl bromopyruvate (5 ml, 1 equivalent) and 20 g of 3 Å of powdered molecular sieves. The reaction was stirred at 70 ° C under a nitrogen atmosphere for 48 h. The mixture was filtered and evaporated to give 12.5 g of crude material. This material was dissolved in THF (200 ml) and treated with 2,6-lutidine (17 ml, 4 equivalents). The reaction was cooled to 0 ° C followed by the addition of trifluoroacetic acid (10.2 ml, 2 equivalents). Stirring was continued for 2 h in a

15 nitrogen atmosphere. Water (200 ml) was added and the reaction was extracted twice with ethyl acetate (600 ml, 150 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent removed by evaporation. The crude material was purified using chloroform: ethyl acetate (1: 1) to give 4.70 g (56%) of the title compound.

20 Example 270B

2- (4-pyridinyl) -1,3-thiazol-4-carbaldehyde

Example 270A (4.7 g, 20.1 mmol) was dissolved in dichloromethane (67 ml) and treated with the slow addition of a

1 M solution of diisobutylaluminum hydride in dichloromethane (38 ml, 1.9 equivalents). The reaction was stirred under a nitrogen atmosphere for 1 h followed by the addition of acetic acid (3.8 ml). The reaction was heated to 25 ° C, quenched with a 10% solution of potassium sodium tartrate (200 ml) and stirred for 1 h. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent removed by evaporation to give

3.73 g of crude material that was purified using chloroform: ethyl acetate (1: 1) to give 2.62 g (69%) of the title compound.

Example 271

4- (5-pyrimidinyl) benzaldehyde

5-Bromopyrimidine (159 mg, 1 mmol) was dissolved in toluene (5 ml) and treated with tetrakis (triphenylphosphine) -palladium (0) (116 mg, 0.1 equivalent) and a 2M solution of sodium carbonate (1 ml, 2 equivalents). The mixture was stirred under an argon atmosphere for 20 min followed by the addition of 3-formylphenyl boronic acid (165 mg, 1.1 equivalents) in ethanol (1 ml). The reaction was heated to 80 ° C and stirred for 16 h. The mixture was filtered and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and the solvent was removed by evaporation. This material was purified using hexanes: dichloromethane (1: 1) followed by dichloromethane: methanol (97: 3) to give 110 mg (60%) of the title compound.

Example 272

2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4-carbaldehyde

Example 272A

Ethyl 5-methyl-isoxazol-3-carbothioamide 2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4-carboxylate (1.0 g, 7.0 mmol) was dissolved in acetone (16 ml ) and treated with ethyl bromopyruvate (1 ml, 1 equivalent) and 3.9 g of 3 Å of powdered molecular sieves. The reaction was stirred at 55 ° C under a nitrogen atmosphere for 18 h. The mixture was filtered and evaporated to give 1.06 g of crude material. This material was dissolved in THF (25 ml), cooled to 0 ° C and treated with 2.6 lutidine (1.5 ml, 3 equivalents). Trifluoroacetic acid (0.9 ml, 1.5 equivalents) was added and stirring continued for 2 h under a nitrogen atmosphere. The reaction was poured into a 1 M solution of sodium bicarbonate and extracted twice with ethyl acetate (75 ml). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent removed by evaporation. The crude material was purified using chloroform: ethyl acetate (1: 1) to give 876 mg (53%) of the title compound.

Example 272B

2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4-carbaldehyde

Example 272A (870 mg, 3.7 mmol) was dissolved in dichloromethane (12 ml) and treated with the dropwise addition of a 1 M solution of diisobutyl aluminum hydride in dichloromethane (7.0 ml, 1.9 equivalent). The reaction was stirred under a nitrogen atmosphere for 1 h followed by the addition of acetic acid (0.7 ml). The reaction was heated to 25 ° C, interrupted with a 10% solution of potassium sodium tartrate (45 ml) and stirred for 1 h. The layers were separated and the aqueous layer was extracted twice with chloroform. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent removed by evaporation to give 670 mg of crude material that was purified using chloroform: hexanes (4: 1) to give 594 g ( 83%) of the title compound.

Example 273

2- (2-pyridinyl) -1,3-thiazol-4-carbaldehyde

Example 273A

Ethyl 2- (2-pyridinyl) -1,3-thiazol-4-carboxylate

2-Picolinamide (3.1 g, 25.4 mmol) was dissolved in toluene (25 ml) and treated with Lawesson's reagent (5.1 g, 0.5 equivalents). The reaction was heated to 85 ° C and stirred for 48 h. The reaction was stopped with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and the solvent was removed by evaporation. This material was dissolved in ethanol (50 ml) and treated with ethyl bromopyruvate (3 ml, approximately 1 equivalent) and 3 Å of powdered molecular sieves (10 g). The reaction was heated at reflux for 16 h. Then, the reaction was filtered and the solvent was removed by evaporation. The material was dissolved in ethyl acetate, washed with a saturated sodium bicarbonate solution, washed with brine and dried over magnesium sulfate. The reaction was filtered and the solvents removed by evaporation. This material was purified using dichloromethane: ethyl acetate (3: 1) to give 1.98 g of the title compound (33%).

Example 273B

2- (2-pyridinyl) -1,3-thiazol-4-carbaldehyde

Example 273A (910 mg, 3.9 mmol) was dissolved in dichloromethane (13 ml) and treated with the dropwise addition of a 1 M solution of diisobutyl aluminum hydride in dichloromethane (7.4 ml, 1.9 equivalent). The reaction was stirred under a nitrogen atmosphere for 1 h followed by the addition of acetic acid (0.8 ml). The reaction was heated to 25 ° C, interrupted with a 10% solution of potassium sodium tartrate (45 ml) and stirred for 1 h. The layers were separated and the aqueous layer was extracted twice with chloroform. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and the solvent removed by evaporation to give 670 mg of crude material. The crude material was purified using chloroform: hexanes (4: 1) to give 390 g (53%) of the title compound.

Example 274

2-Isopropyl-1,3-thiazol-4-carbaldehyde

Example 274 was prepared using the procedures described in the Journal of Medicinal Chemistry, 41, 4; 602-617 (1998).

Example 275

(1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (4-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

Example 275A

2-((2S, 3S) -3 - {[(benzyloxy) carbonyl] amino} -2-hydroxy-4-phenylbutyl) -2- (4-nitrobenzyl) tert-butyl hydrazinecarboxylate

N '- (4-Nitro-benzyl) -hydrazinecarboxylic acid tert-butyl ester (1 g, 3.7 mmol) was dissolved in isopropanol (30 ml.) And treated with (2S, 3S) -3-N- benzyloxycarbonylamino-1,2-epoxy-4-phenylbutane (1.2 g, 1.1 equivalents) at 65 ° C for 16 h. The mixture was cooled to 25 ° C, and the solids filtered and dried in vacuo to give 1.5 g (71%) of the title compound.

Example 275B

(1S, 2S) -1-Benzyl-2-hydroxy-3- [2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} -1- (4-nitrobenzyl) hydrazino] benzyl propylcarbamate

Example 275A (0.355 g, 0.63 mmol) was dissolved in THF (6.3 ml) and treated with 4 N HCl (1.2 ml) at 60 ° C for 16

h. The solvents were evaporated, the crude residue was dissolved in THF (3.2 ml) and treated with DEPBT (0.28 g, 1.5 equivalents), triethylamine (0.26 ml, 3 equivalents) at 25 ° C for 25 ° C. 3 h The solvents were evaporated, and the crude residue was purified using HPLC reverse phase chromatography using water (0.1% trifluoroacetic acid): acetonitrile (95: 5) to acetonitrile (100%) to give 344 mg (86%) of the title compound.

Example 275C

(1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

A solution of Example 275B (0.29 g, 0.456 mmol) in methanol (4.6 ml) was treated with Pd / C (29 mg, 10%) and stirred at 25 ° C in a hydrogen balloon for 2.5 h. The catalyst was filtered, rinsed with methanol, and the solvents evaporated to give 0.17 g of crude product that was used in the next step. The crude material was dissolved in DMF (3.6 ml) and treated with EDAC (112 mg, 2 equivalents), HOBT (97 mg, 2 equivalents), N-methyl morpholine (251 μl, 5 equivalents) and Example 32 (123 mg, 1 equivalent) at 25 ° C for 16 h. The solvents were evaporated, and the residue was partitioned between 1 N NaHCO3 and ethyl acetate. The organic layer was separated, washed with brine, dried over magnesium sulfate, and the solvents evaporated to give two products, one being the amine of Example 275C and the other, the para-aminobenzyl compound. This mixture was subjected to THF: 4 N HCl (1: 2) at 50 ° C for 3 h to give 85 mg (27%) of the title compound.

Example 275D

(1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (4-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

A solution of Example 275C (13.8 mg, 0.02 mmol) in 1,2-dichloroethane (0.25 ml) was treated with 2- (4-pyridyl) thiazole 4carboxaldehyde (4.6 mg, 1.2 equivalents) ), sodium triacetoxy borohydride (12.7 mg, 3 equivalents) and acetic acid (2.3 μl) and stirred at 25 ° C for 16 h. The mixture was partitioned between dichloromethane and saturated NaHCO3. The organic layer was separated, dried over magnesium sulfate, filtered, and the solvents evaporated. The residue was purified by HPLC reverse phase chromatography using water (0.1% trifluoroacetic acid): acetonitrile (95: 5) to acetonitrile (100%) to give 3 mg (14%) of the title compound. 1 H NMR (300 MHz, CD3OD) δ ppm 0.87 (s, 9 H), 0.91 (s, 9 H), 2.36 (d, J = 8.82 Hz, 1 H), 2.85 (m, 5 H), 3.07 (m, 1 H), 3.14 (m, 1 H), 3.28 (m, 3 H), 3.46 (s, 3 H), 3.61 (s, 3 H), 3.76 (s, 1 H), 3.85 (s, 1 H), 4.05 (s, 1 H), 4.16 (m, 3 H), 4.46 (m, 2 H), 4.71 (s, 2 H), 7.08 (m, 3 H), 7.16 (m, 2 H), 7.38 (s, 1

5 H), 7.73 (s, 1 H), 7.95 (m, 2 H), 8.64 (m, 2 H).

The compounds listed in Table 11, in which X3 represents the point of attachment to the core structure (K), were prepared by the procedure illustrated in Example 275D, substituting 2- (4-pyridyl) thiazole 4-carboxyaldehyde for corresponding aldehydes available in the market:

10 Table 11

Ex. Nº

R3  Ex. Nº R3

276

277

278

279

Example 280

15 (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole -4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

Example 280A

20 (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole -4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

A solution of Example 19A (0.46 g, 0.987 mmol) in dichloromethane: trifluoroacetic acid (9 ml, 2: 1) was stirred at 25 ° C for 4 h. The solvents were evaporated, the crude residue was dissolved in DMF (10 ml) and treated with Example 29 (0.37 g, 1.1 equivalents), EDAC (0.338 g, 2 equivalents), HOBT (0, 29 g, 2 equivalents) and N-methyl morpholine (0.76 ml, 5 equivalent) at 25 ° C for 16 h. The solvents were evaporated, and the crude residue was partitioned between ethyl acetate and 1 N sodium bicarbonate. The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and the solvents evaporated to give 0.475 g (70%) of the title compound.

30 Example 280B

(1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3

methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

A solution of Example 280A (20 mg, 0.029 mmol) in 1,2-dichloroethane (0.3 ml) was treated with isovaleraldehyde (6.2 μl, 2 equivalents), acetic acid (3.3 μl, 2 equivalents) , and sodium triacetoxyborohydride (18.5 mg, 3 equivalents) at 25 ° C for 16 h. The mixture was partitioned between dichloromethane and saturated sodium bicarbonate. The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and the solvents evaporated. The residue was purified by HPLC reverse phase chromatography using water (0.1% TFA): acetonitrile (95: 5) to acetonitrile

40 (100%) to give 8 mg (36%) of the title compound. 1 H NMR (300 MHz, DMSO-d6) δ ppm 0.78 (dd, J = 13.79, 6.43 Hz, 12 H), 0.91 (m, 9 H), 1.25 (m, 3 H), 1.62 (m, 1 H), 1.77 (d, J = 8.82 Hz, 1 H), 2.58 (m, 3 H), 2.69 (m, 4 H), 2.79 (m, 2 H), 3.09 (m, 3 H), 3.37 (s, 3 H), 3.81 (m, 2 H), 3.95 (m, 2 H), 4.10 (s, 1 H), 4.36 (m, 2 H), 4.66 (s, 1 H), 7.06 (m, 5 H), 7.20 (m, 1 H), 7.44 (m, 1 H), 8.96 (s, 2 H), 9.17 (s, 1 H), 9.48 (s, 1 H).

The compounds listed in Table 12, in which X3 represents the point of attachment to the core structure (L), were prepared by the procedure illustrated in Example 280B, substituting isovaleraldehyde for the corresponding commercially available aldehydes:

Table 12

Ex. Nº

R3  Ex. Nº R3

281

282

Example 283

5 (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) ) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate methyl

Example 283A

10 (1S, 2S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2 -pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2-methylbutylcarbamate methyl

A solution of Example 127 (0.74 g) in methanol (5 ml) was treated with 4 N HCl (0.25 ml, 1 equivalent) and catalyst

15 Pearlman (150 mg, 20% by weight) and stirred in a hydrogen balloon at 25 ° C for 4 h. The mixture was filtered, rinsed with methanol (10 ml) and the solvents evaporated. The residue was purified using 10% methanol / CHCl3 to give 0.47 g (73%) of the title compound.

Example 283B

20 (1S, 2S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2 -pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate methyl

A solution of Example 283A (50 mg, 0.45 mmol) in 1,2-dichloroethane (1 ml) and treated with p-anisaldehyde (16 mg,

25 1.5 equivalents), acetic acid (5 μl, 2 equivalents) and sodium triacetoxyborohydride (32 mg, 2 equivalents) at 25 ° C for 16 h. The mixture was quenched with 10% NaHCO3 (2 ml) and CHCl3. The organic layer was separated, dried over sodium sulfate, filtered and the solvents evaporated. The residue was purified using 5% methanol / CHCl3 to give 53 mg (90%) of the title compound.

30 Example 284

(1S, 2S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2- pyridinyl) methyl] -2-oxo-1

imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2-methylbutylcarbamate methyl

A solution of Example 283A (50 mg, 0.075 mmol) in dichloroethane (1 ml) was treated with isovaleraldehyde (10 mg, 1.5 equivalents), acetic acid (5 μl, 2 equivalents) and sodium triacetoxy borohydride (32 mg, 2 equivalents) and stirred at 25 ° C for 16 h. The mixture was quenched with 10% NaHCO3 (2 ml) and CHCl3. The organic layer was separated, dried over sodium sulfate and the solvents evaporated. The residue was purified using 5% methanol / CHCl3 to give 49 mg (89%) of the title compound.

40 Example 285

(1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2- pyridinyl) methyl] -2-oxo-1

imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl

Example 283A (300 mg, 0.45 mmol) was dissolved in dichloroethane (1 ml) and treated with 4- (2-pyridyl) benzaldehyde (0.125 g, 1.5 equivalents), acetic acid (40 μl, 2 equivalent) and sodium triacetoxy borohydride (0.19 g, 2 equivalents) at 25 ° C for 16 h. The mixture was quenched with 10% NaHCO3 (2 ml) and CHCl3. The organic layer was separated, dried over sodium sulfate, and the solvents evaporated. The residue was purified using methanol at

50% / CHCl3 to give 0.273 g (72%) of the title compound.

Example 286

(1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] -2-Oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-methyl dimethylpropylcarbamate

Example 286A

(1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] -2-Oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-methyl dimethylpropylcarbamate

Example 139 (0.122 g, 0.146 mmol) was dissolved in methanol (4 ml) and treated with Pearlman catalyst (30 mg) and 4 N HCl (40 μl) with a hydrogen balloon at 25 ° C for 4 h. The mixture was filtered, rinsed with methanol, and the solvents evaporated. The residue was purified using 10% methanol / CHCl3 to give 98 mg (100%) of the title compound.

Example 286B

(1S) -1 - {[2 - {(2S, 3R) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] -2-Oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-methyl dimethylpropylcarbamate

Example 286A (45 mg, 0.067 mmol) was dissolved in 1,2-dichloroethane (1 ml) and treated with p-anisaldehyde (15 mg, 1.2 equivalents) and acetic acid (5 μl, 3 equivalents) followed by sodium triacetoxy borohydride (30 mg, 3 equivalents) at 25 ° C for 16 h. The mixture was partitioned between saturated NaHCO3 and dichloromethane, the organic layer was separated, dried over sodium sulfate, filtered, and the solvents evaporated. The residue was purified using 3% methanol / CHCl3 to give 36 mg (55%) of the title compound.

Example 287

(1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

Example 287 was prepared using the procedure of Example 286B, substituting p-anisaldehyde for isovaleraldehyde.

Example 288

(1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

Example 288A

(1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

Example 94 (0.17 g, 0.2 mmol) was dissolved in methanol (5 ml) and treated with 4 N HCl (52 μl, 1 equivalent) and Pd (OH) 2 (34 mg, 20% by weight ) and a hydrogen balloon at 25 ° C for 16 h. The mixture was filtered, rinsed with methanol (10 ml), and the solvents evaporated. The residue was purified using 3% methanol / CHCl3 to give 100 mg (74%) of the title compound.

Example 288B

(1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

Example 288A (40 mg) was dissolved in dichloroethane (1 ml) and treated with p-anisaldehyde (12 μl, 1.5 equivalents), acetic acid (7 μl, 2 equivalents) and sodium triacetoxy borohydride at 25 ° C for 16 h. The mixture was quenched with 10% NaHCO3 (2 ml) and CHCl3. The organic layer was separated, dried over sodium sulfate, filtered and the solvents evaporated. The residue was purified using 5% methanol / CHCl3 to give 22 mg (46%) of the title compound.

Example 289

(1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl

Example 289 was prepared using the procedure of Example 288B, substituting p-anisaldehyde for isovaleraldehyde.

Example 290

(1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-pyridinylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl

Example 209 was dissolved in DMF (0.15 ml) and treated with 4-bromomethylpyridine (5 mg, 1.3 equivalents) and N, Ndiisopropylethylamine (8 μl, 3 equivalents) at 25 ° C for 1 h followed by 50 ° C for 16 h. The mixture is distributed between water and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered and the solvents were evaporated The residue was purified using 10% methanol / CHCl3 to give 7 mg (61%) of the title compound.

NMR data

Example 71 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (s, 9 H), 0.93 (m, 9 H), 2.62 (dd, J = 12.13, 2.94 Hz, 2 H), 2.82 (m, 2 H), 2.86 (d, J = 1.84 Hz, 1 H), 3.10 (m, 2 H), 3.31 (m, J = 9.19 Hz, 1 H), 3, 59 (d, J = 9.19 Hz, 1 H), 3.63 (s, 3 H), 3.85 (s, 3 H), 3.99 (s, 1 H), 4.00 (m, 2 H), 4.12 (m, 1H), 4.69 (d, J = 8.46 Hz, 2 H), 4.74 (s, 1 H), 5.28 (d, J = 8.09 Hz, 1 H), 6.22 (d, J = 9.56 Hz, 1 H), 6.41 (s, 1 H), 7.01 (m, 3 H), 7.10 (m, 2 H) , 7.30 (m, 4 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.74 (m, 3 H), 7.96 (d, J = 8.46 Hz, 2 H), 8.69 (d, J = 4.41 Hz, 1 H). Example 72 1 H NMR (300 MHz, CDCl 3) δ ppm 0.75 (d, J = 6.25 Hz, 3 H), 0.82 (m, 9 H), 0.98 (m, 1 H), 1 , 32 (m, 1 H), 1.90 (d, J = 6.99 Hz, 1 H), 2.63 (dd, J = 12.50, 2.94 Hz, 1 H), 2.82 (dd, J = 12.50, 10.30 Hz, 2 H), 2.91 (d, J = 6.62 Hz, 3 H), 3.01 (dd, J = 7.72, 3.31 Hz, 2 H), 3.06 (m, 3 H), 3.60 (s, 3 H), 3.63 (d, J = 3.31 Hz, 1 H), 3.84 (d, J = 11.03 Hz, 1 H), 4.00 (m, 2 H), 4.12 (m, 1 H), 4.28 (d, J = 15.08 Hz, 1 H), 4.46 (d, J = 15.08 Hz, 1 H), 4.75 (s, 1 H), 5.27 (d, J = 8.82 Hz, 1 H), 6.57 (d, J = 9.56 Hz, 1 H), 6.71 (s, 1 H), 7.18 (m, 7 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.63 (m, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.53 (m, 2 H). Example 73 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 7.72 Hz, 12 H), 0.85 (m, 3 H), 1.03 (m, 1 H), 1 , 40 (m, 1 H), 1.91 (s, 1 H), 2.54 (s, 3 H), 2.61 (dd, J = 12.32, 3.86 Hz, 1 H), 2.81 (dd, J = 12 , 69, 10.11 Hz, 1 H), 2.92 (t, J = 8.09 Hz, 3 H), 3.11 (m, J = 4.04 Hz, 1 H), 3.17 (m, 3 H), 3.59 (s, 3 H), 3.64 (m, 2 H), 3.91 (m, 1 H), 3.97 (d, J = 6.62 Hz, 1 H), 4.07 (m, 1 H), 4.48 (s, 2 H), 4.79 (s, 1 H), 5.26 (d, J = 8.82 Hz, 1 H), 6.59 (d, J = 9.19 Hz, 1 H), 7.06 (dd, J = 12.13, 7.35 Hz, 2 H), 7.19 (m, 6 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.54 (t, J = 7, 72 Hz, 1 H), 7.74 (m, 2 H), 7.94 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 74 1 H NMR (300 MHz, CDCl 3) δ ppm 0.64 (d, J = 6.62 Hz, 3 H), 0.75 (m, 3 H), 0.78 (m, 3 H), 0 , 84 (m, 3 H), 0.96 (m, 2 H), 1.63 (d, J = 3.31 Hz, 2 H), 2.62 (dd, J = 12.50, 3.68 Hz, 1 H), 2, 88 (m, 5 H), 3.10 (m, 1 H), 3.22 (m, 2 H), 3.47 (s, 3 H), 3.59 (s, 3 H), 3.69 (m, 1 H), 3.88 (d, J = 11.03 Hz, 1 H), 3.97 (d, J = 18.02 Hz, 2 H), 4.08 (m, 2 H), 4.47 (s, 3 H), 4.69 (s, 2 H), 5.10 (d, J = 8.82 Hz, 1 H), 6.57 (d, J = 9.19 Hz, 1 H), 6.75 (s, 1 H), 7.14 (m, 7 H), 7.44 (d, J = 8.46 Hz, 2 H), 7.72 (d, J = 7.72 Hz, 1 H), 7.79 (m, 1 H), 7.94 (d, J = 8.46 Hz , 2 H), 8.72 (d, J = 4.04 Hz, 1 H). Example 75 1 H NMR (300 MHz, CDCl 3) δ ppm 0.76 (d, J = 6.62 Hz, 3 H), 0.81 (t, J = 7.35 Hz, 3 H), 1.00 ( m, 1 H), 1.38 (s, 9 H), 1.92 (s, 1 H), 2.52 (s, 1 H), 2.71 (d, J = 11.03 Hz, 1 H), 2.80 (m, 1 H), 2.86 (d, J = 7.72 Hz, 1 H), 2.92 (d, J = 7.72 Hz, 1H), 3.04 (m, 2 H), 3.08 (m, 1 H), 3.66 (d, J = 12.50 Hz, 1 H), 3.91 (d, J = 11.03 Hz, 1 H), 3.98 (s, 2 H), 4.09 (d, J = 9.93 Hz, 1 H), 4.48 (s, 1 H), 4.75 (d, J = 15.44 Hz, 1 H), 4.88 (m, 1 H), 5.33 (s, 1 H), 6.44 (d, J = 8.82 Hz, 1H), 7.08 (m, 3 H), 7.14 (m, 2 H), 7.22 (m, 1 H), 7.28 (s, 1 H), 7.41 (d , J = 8.09 Hz, 2 H), 7.58 (m, 1 H), 7.74 (m, 4 H), 7.96 (d, J = 8.09 Hz, 2 H), 8.12 (d, J = 8.46 Hz, 1 H), 8.19 (d, J = 8.09 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H), 8.86 (d, J = 4.41 Hz, 1 H). Example 76 1 H NMR (300 MHz, CDCl 3) δ ppm 0.65 (d, J = 6.99 Hz, 3 H), 0.75 (t, J = 7.17 Hz, 3 H), 0.95 ( s, 9 H), 1.28 (m, 2 H), 1.68 (m, 1 H), 2.62 (m, 2 H), 2.83 (m, 3 H), 3.11 (m, 2 H), 3.32 (m, 1 H), 3.62 (s, 3 H), 3.68 (m, 1 H), 3.85 (s, 3 H), 3.93 (d, J = 13.60 Hz, 1 H), 4.00 (s, 1 H), 4.05 (m, 1 H), 4.15 (c, J = 8 , 3 3 Hz, 1 H), 4.69 (m, 3 H), 5.10 (d, J = 8.09 Hz, 1 H), 6.26 (d, J = 9.56 Hz, 1 H), 6.58 (s, 1 H), 7.01 (m, 3 H), 7.10 ( m, 2 H), 7.29 (m, 3 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.74 (m, 4 H), 7.96 (d, J = 8.46 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 77 1 H NMR (300 MHz, CDCl 3) δ ppm 0.65 (d, J = 6.62 Hz, 3 H), 0.74 (t, J = 7.17 Hz, 3 H), 0.88 ( dd, J = 13.05, 3.86 Hz, 1 H), 0.96 (s, 9 H), 1.30 (s, 1 H), 1.64 (s, 1 H), 2.65 (m, 3 H), 2.85 (m, 4 H), 3.14 (m, 2 H), 3.35 (m, 1 H), 3.48 (s, 3 H), 3.62 (s, 3 H), 3.68 (m, 1 H), 3.92 (d, J = 13.60 Hz, 1 H), 4.03 (s, 1 H), 4.10 (m, 1 H), 4.50 (s, 2 H), 4.71 (s, 3 H), 5.09 (d, J = 8.46 Hz, 1 H), 6.30 (d, J = 9.19 Hz, 1 H), 6.59 (s, 1 H), 7.16 (m, 7 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H). Example 78 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (s, 9 H), 0.95 (s, 9 H), 2.61 (dd, J = 12.50, 2.94 Hz, 2 H), 2.84 (m, 4 H), 3.14 (m, 2 H), 3.34 (d, J = 4.04 Hz, 1 H), 3.48 (d, J = 2.57 Hz, 3 H), 3, 62 (s, 3 H), 3.94 (d, J = 13.60 Hz, 1 H), 4.02 (s, 2 H), 4.09 (m, 1 H), 4.50 (s, 2 H), 4.71 (s, 3 H), 5.27 (d, J = 8, 46 Hz, 1 H), 6.27 (d, J = 9.56 Hz, 1 H), 6.44 (s, 1 H), 7.10 (m, 6 H), 7.23 (m, 1 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.74 (m, 2 H) , 7.95 (d, J = 8.46 Hz, 2 H), 8.69 (d, J = 4.78 Hz, 1H). Example 79 1 H NMR (300 MHz, CDCl 3) δ ppm 0.64 (d, J = 6.62 Hz, 3 H), 0.77 (c, J = 6.50 Hz, 9 H), 0.88 ( m, 4 H), 1.04 (m, 1 H), 1.35 (m, 2 H), 1.90 (s, 1 H), 2.59 (m, 1 H), 2.78 (m, 1 H), 2.88 (d, J = 6.99 Hz, 3 H), 3.08 (m, 2 H), 3.61 (s, 3 H), 3.67 (m, 1 H), 3.84 (m, 2 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.10 (d, J = 7.72 Hz, 1 H), 4.81 (m, 2 H), 5.09 (d, J = 9.19 Hz, 1 H), 6.56 (d, J = 9.56 Hz, 1 H), 6.72 (s, 1 H), 7.09 (m, 5 H), 7.24 (m, 3 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.59 (m, 1 H), 7.72 (t, J = 6.99 Hz, 1 H), 8.14 (d, J = 7.72 Hz, 1 H), 8.19 (d, J = 7 , 72 Hz, 1 H), 8.88 (d, J = 4.04 Hz, 1H). Example 80 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 2.94 Hz, 9 H), 0.87 (m, 6 H), 0.97 (d, J = 6.62 Hz, 1 H), 1.38 (m, 1 H), 1.89 (s, 1 H), 2.60 (dd, J = 12.50, 3.31 Hz, 1 H), 2.79 (m, 1 H) , 2.90 (d, J = 8.09 Hz, 3 H), 3.05 (m, 3

H), 3.58 (s, 1 H), 3.62 (s, 3 H), 3.87 (m, 2 H), 3.99 (m, 1 H), 4.12 (m, 1 H), 4.29 (d, J = 15.08 Hz, 1 H), 4.46 (m, 1 H), 4.72 (s, 1 H), 5.27 (d, J = 8.46 Hz, 1 H), 6.54 (d, J = 9.93 Hz, 1 H), 6.60 (s, 1 H), 7.15 (m, 5 H), 7.30 (m, 6 H), 7.63 (m, 1 H), 8.54 (m, 2 H). Example 81 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (m, 12 H), 0.87 (m, 3 H), 1.02 (m, 1 H), 1.27 (d, J = 3.68 Hz, 1 H), 1.41 (m, 1 H), 1.89 (s, 1 H), 2.54 (s, 3 H), 2.59 (m, 1 H), 2.78 (dd, J = 12, 50, 10.30 Hz, 1 H), 2.91 (m, 2 H), 3.16 (m, 2 H), 3.59 (s, 2 H), 3.61 (s, 3 H), 3.89 (s, 1 H), 3.95 (m, 2 H), 4.07 (c, J = 8.70 Hz, 1 H), 4.47 (m, 2 H), 4.75 (s, 1 H), 5.26 (d, J = 9.93 Hz, 1 H), 6.54 (d, J = 9.93 Hz, 2 H), 7.06 (dd, J = 12.50, 7.72 Hz , 2 H), 7.12 (m, 1 H), 7.19 (m, 4 H), 7.29 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 82 1 H NMR (300 MHz, CDCl 3) δ ppm 0.62 (t, J = 6.80 Hz, 3 H), 0.77 (m, 6 H), 0.86 (t, J = 7.35 Hz, 3 H), 1.02 (m, 1 H), 1.37 (m, 1 H), 1.91 (m, 1 H), 2.60 (dd, J = 12.32, 2.76 Hz, 1 H), 2, 80 (m, 1 H), 2.93 (m, 4 H), 3.06 (m, 4 H), 3.58 (s, 1 H), 3.61 (s, 3 H), 3.70 (m, 1 H), 3.85 (m, 2 H), 3.99 (m, 1 H), 4.13 (m, 1 H), 4.29 (d, J = 15.08 Hz, 1 H), 4.45 (m, 1 H), 4.73 (s, 1 H), 5.10 (d, J = 8.09 Hz, 1 H), 6.57 (d, J = 9.19 Hz, 1 H) , 6.74 (s, 1 H), 7.14 (m, 5 H), 7.29 (m, 6 H), 7.63 (t, J = 7.54 Hz, 1H), 8.53 (m, 2 H). Example 83 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (s, 9 H), 0.95 (s, 9 H), 1.27 (d, J = 3.68 Hz, 1 H), 2 , 48 (s, 3 H), 2.64 (d, J = 2.94 Hz, 2 H), 2.87 (m, 2 H), 3.14 (m, 2 H), 3.34 (s, 1 H), 3.58 (s, 1 H), 3.62 (s, 3 H), 3.99 (m, 2 H), 4.02 (s, 1 H), 4.11 (d, J = 6.62 Hz, 1 H), 4.57 (s, 2 H), 4.73 (s, 1 H), 5.27 (d, J = 9.19 Hz, 1 H), 6.27 (d, J = 9.56 Hz, 1 H), 6.44 (s, 1 H), 6.55 (s, 1 H), 7.10 (m, 5 H), 7.22 (m, 1 H), 7.26 (s, 1 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.69 (d, J = 4.04 Hz, 1 H). Example 84 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (d, J = 8.82 Hz, 12 H), 0.86 (m, 5 H), 0.88 (m, 3 H), 1 , 05 (m, 1 H), 1.42 (m, 1 H), 1.94 (m, 1 H), 2.54 (s, 3 H), 2.54 (dd, J = 12.32, 3.49 Hz, 1 H) , 2.75 (m, 1 H), 2.89 (d, J = 6.62 Hz, 2 H), 3.14 (m, 2 H), 3.54 (s, 1 H), 3.61 (s, 3 H), 3.78 (s, 3 H), 3.85 (d, J = 7.72 Hz, 1 H), 3.91 (m, 1 H), 4.06 (m, 1 H), 4.47 (m, 2 H), 4.71 (d, J = 8.82 Hz, 1 H), 5.26 (d, J = 10.30 Hz, 1 H), 6.54 (m, J = 9.56 Hz, 2 H), 6.83 (d, J = 8.82 Hz, 2 H), 7.08 (m, 2 H), 7.16 (m, 3 H), 7.20 (d, J = 8.82 Hz, 2 H), 7.54 (t, J = 7 , 54 Hz, 1 H). Example 85 1 H NMR (300 MHz, DMSO d6) δ ppm 0.68 (s, 9 H), 0.86 (s, 9 H), 2.72 (m, 4 H), 2.72 (m, 3 H), 3.09 (m, 1 H), 3.24 (m, 1 H), 3.50 (s, 3 H), 3.67 (d, J = 9.19 Hz, 2 H), 3.98 (s, 1 H), 4.04 (s, 1 H), 4.12 (s, 1 H), 4.42 (d, J = 15.44 Hz, 1 H), 4.53 (d, J = 15.08 Hz, 1 H), 4.85 (d, J = 3.31 Hz, 1 H), 6.98 (m, 1 H), 7.09 (m, 5 H), 7.32 (m, 1 H), 7.45 (d, J = 8.09 Hz, 2 H), 7.53 (dd, J = 8.82, 4.78 Hz, 1 H), 7.60 (s, 1 H), 7.65 (d, J = 9 , 19 Hz, 1 H), 7.87 (m, 2 H), 7.98 (d, J = 8.46 Hz, 2 H), 8.29 (m, 1 H), 8.66 (m, 2 H), 9.13 (s, 2 H). Example 86 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.78 (s, 9 H), 0.91 (s, 9 H), 0.98 (m, 1 H), 2.42 (t, J = 9.01 Hz, 1 H), 2.82 (m, 5 H), 3.06 (m, 1 H), 3.16 (c, J = 9.19 Hz, 1 H), 3.59 (s, 3 H), 3.73 (m, 1 H), 3.83 (s, 1 H), 3.99 (m, 2 H), 4.07 (m, 1 H), 4.19 (m, 1 H), 4.47 (m, 2 H), 4.55 (s, 3 H), 4.69 (s, 2 H), 7.09 (m, 4 H), 7.18 (m, 3 H), 7.23 (d, J = 7.35 Hz, 1 H), 7.35 (m, 1 H), 7.45 (d, J = 7.72 Hz, 1 H), 7.54 (d, J = 8.46 Hz, 2 H), 7.81 (m, 2 H), 7.86 (d, J = 2.21 Hz, 1 H), 7.89 (d, J = 1.84 Hz, 1 H). Example 87 1 H NMR (500 MHz, DMSO d6) δ ppm 0.66 (m, 12 H), 0.75 (t, J = 7.63 Hz, 3 H), 0.92 (m, 1 H), 1.27 (m, 2 H), 1.76 (m, 1 H), 2.65 (dd, J = 13.43, 9.77 Hz, 1 H), 2.71 (s, 3 H), 2.76 (m, 9 H), 3.03 (m, 1 H) 1 3.15 (m, 1 H), 3.21 (c, J = 8.54 Hz, 1 H), 3.65 (m, 2 H), 3.95 (m, 2 H), 4.01 (m, 2 H), 4.09 (s, 1 H) , 4.38 (d, J = 15.87 Hz, 1 H), 4.47 (d, J = 15.87 Hz, 1 H), 6.90 (d, J = 9.16 Hz, 1 H), 7.03 (t, J = 6.41 Hz, 1 H), 7.10 (m, 4 H), 7.40 (m, 2 H), 7.44 (s, 1 H), 7.48 (d, J = 8.54 Hz, 2 H), 7.97 (d, J = 7.93 Hz, 2 H), 8.68 (d, J = 4.88 Hz, 1 H), 9, 12 (s, 1 H). Example 88 1 H NMR (500 MHz, CDCl 3) δ ppm 0.80 (s, 9 H), 0.94 (s, 9 H), 1.63 (m, 2 H), 2.55 (s, 3 H ), 2.65 (m, 2 H), 2.81 (m, 1 H), 2.90 (m, 3 H), 2.99 (c, J = 8.95 Hz, 1 H), 3.32 (m, 1 H), 4.00 (m, 4 H), 4.12 (c, J = 7.93 Hz, 1 H), 4.31 (d, J = 15.26 Hz, 1 H), 4.38 (d, J = 15.26 Hz, 1 H), 4.72 (s, 1 H), 5.29 (m, 1 H) , 6.29 (d, J = 9.16 Hz, 1 H), 6.51 (s, 1 H), 7.09 (m, 3 H), 7.16 (d, J = 6.10 Hz, 4 H), 7.23 (m, 1 H), 7.43 (d, J = 7, 93 Hz, 2 H), 7.55 (dd, J = 7.93, 2.44 Hz, 1 H), 7.70 (d, J = 7.93 Hz, 1 H), 7.75 (m, 1 H), 7.95 (d, J = 8.54 Hz, 2 H), 8.40 (s, 1 H), 8.69 (d, J = 3.66 Hz, 1 H). Example 89 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.78 (s, 9 H), 0.91 (s, 9 H), 1.35 (m, 1 H), 1.52 (s, 3 H), 1.53 (s, 3 H), 2.36 (m, 1 H), 2.82 (m, 6 H), 3.06 (m, 1 H), 3.22 (dd, J = 17.83, 8.64 Hz, 1 H), 3.29 (m, 3 H), 3.59 (s, 3 H), 3.83 (m, 1 H), 3.97 (d, J = 13.60 Hz, 1 H), 4.04 (t, J = 5.33 Hz, 2 H), 4.20 (m, 1 H) , 4.41 (d, J = 15.81 Hz, 1 H), 4.59 (d, J = 15.44 Hz, 1 H), 7.09 (m, 2 H), 7.18 (m, 3 H), 7.35 (m, 1 H), 7.53 (m, 2 H), 7 , 76 (d, J = 7.72 Hz, 2 H), 7.82 (m, 3 H), 7.88 (m, 2 H), 8.59 (d, J = 4.78 Hz, 1 H). Example 90 1 H NMR (300 MHz, DMSO-d6) δ ppm 0.66 (m, J = 8.09 Hz, 12 H), 0.74 (t, J = 7.17 Hz, 3 H), 0, 89 (m, 3 H), 1.25 (m, 5 H), 1.75 (s, 1 H), 2.76 (m, 5 H), 3.04 (s, 1 H), 3.19 (m, 1 H ), 3.50 (s, 3 H), 3.67 (d, J = 9.93 Hz, 2 H), 3.96 (m, 2 H), 4.03 (s, 1 H), 4.15 (m, 1 H), 4.48 (m, 2 H), 4.95 (d, J = 3, 31 Hz, 1 H), 7.04 (m, 5 H), 7.32 (m, 1 H), 7.45 (d, J = 8.46 Hz, 3 H), 7.67 (m, 2 H), 7.72 (s, 1 H), 7.86 (m, 2 H), 7.99 (d, J = 8.09 Hz, 2 H), 8.57 (d, J = 5.15 Hz, 1 H), 8.64 (d, J = 4.04 Hz, 1 H), 9.13 (s, 1 H). Example 91 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 7.35 Hz, 12 H), 0.86 (m, 3 H), 1.28 (m, 6 H), 1 , 39 (m, 2 H), 1.96 (d, J = 38.24 Hz, 1 H), 2.63 (d, J = 2.57 Hz, 1 H), 2.81 (m, 1 H), 2.90 (m, 3 H), 3.16 (m, 2 H), 3.90 (d, J = 11.40 Hz, 1 H), 3.98 (d, J = 9.56 Hz, 1 H), 4.07 (s, 1 H), 4.50 (s, 2 H), 4.80 (s, 1 H), 5.30 (m, 1 H), 6.59 (m, 2 H), 7.17 (m, 5 H), 7.23 (m, 3 H), 7.30 (d, J = 7.72 Hz, 1 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.71 (m, 2 H), 7.94 (d, J = 8.46 Hz, 2 H), 8.54 (m, 1 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 92 1 H NMR (300 MHz, CDCl 3) δ ppm 0.72 (d, J = 6.62 Hz, 3 H), 0.81 (m, 3 H), 0.81 (s, 9 H), 0 , 94 (m, 1 H), 1.26 (m, 1 H), 1.84 (s, 1 H), 2.60 (dd, J = 9.56, 2.94 Hz, 1 H), 2.76 (m, 1 H) , 2.90 (m, 2 H), 3.35 (d, J = 18.02 Hz, 1 H), 3.61 (m, 2 H), 3.63 (s, 3 H), 3.99 (m, 4 H), 4.16 (m, J = 6.62 Hz, 1 H), 4.81 (m, 3 H), 5.26 (d, J = 8.46 Hz, 1 H), 6.29 (d, J = 9.56 Hz, 1 H), 6.44 (s, 1 H), 7.14 (m, 6 H), 7.22 (t, J = 3.31 Hz, 2 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.64 (m, 1 H), 7.75 (m, 2 H), 7.96 (d, J = 8.09 Hz, 2 H), 8.52 (d, J = 4.78 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 93 1 H NMR (300 MHz, CDCl 3) δ ppm 0.75 (d, J = 6.62 Hz, 3 H), 0.82 (m, 12 H), 0.97 (m, 1 H), 1 , 34 (m, 1 H), 1.88 (d, J = 10.30 Hz, 1 H), 2.53 (s, 3 H), 2.62 (m, 1 H), 2.81 (m, 1 H), 2.88 (m, 3 H), 3.02 (m, 3 H), 3.60 (s, 3 H), 3.63

(s, 1 H), 3.85 (d, J = 11.40 Hz, 1 H), 4.00 (m, 2 H), 4.09 (m, 1 H), 4.24 (d, J = 15.08 Hz, 1 H), 4.41 (m, 1 H), 4.78 (s, 1 H), 5.28 (d, J = 12.87 Hz, 1 H), 6.57 (d, J = 9.56 Hz, 1 H), 6.68 (s, 1 H), 7.13 (m, 6 H), 7.22 (m, 1 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.52 (dd, J = 7.91.2.39 Hz, 1 H), 7.74 (m, 2 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.38 (d, J = 1.84 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 94 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (s, 9 H), 0.94 (s, 9 H), 2.55 (s, 3 H), 2.63 (m, 2 H ), 2.86 (m, 4 H), 2.98 (m, 2 H), 3.32 (m, 1 H), 3.62 (s, 3 H), 4.00 (m, 3 H), 4.09 (d, J = 10, 66 Hz, 1 H), 4.34 (m, 2 H), 4.74 (s, 1 H), 5.29 (d, J = 7.72 Hz, 1 H), 6.29 (d, J = 9.19 Hz, 1 H), 6.47 (s, 1 H), 7.08 (m, 2 H) , 7.16 (m, 4 H), 7.23 (dd, J = 6.80, 2.02 Hz, 1 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.54 (dd, J = 7.72, 2.21 Hz, 1 H), 7.75 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.39 (d, J = 1.84 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 95 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.78 (s, 9 H), 0.90 (d, J = 5.52 Hz, 9 H), 2.31 (t, J = 9 , 38 Hz, 1 H), 2.81 (m, 8 H), 2.95 (m, 1 H), 3.07 (c, J = 8.82 Hz, 1 H), 3.59 (s, 3 H), 3.72 (s, 1 H), 3.84 (d, J = 8.82 Hz, 1 H), 3.99 (m, 2 H), 4.08 (d, J = 3.68 Hz, 1 H), 4.18 (m, 1 H), 4.74 (d, J = 15.08 Hz, 1 H) , 5.02 (d, J = 15.44 Hz, 1 H), 6.82 (t, J = 7.17 Hz, 2 H), 6.91 (t, J = 7.17 Hz, 1 H), 7.04 (d, J = 6.99 Hz, 2 H), 7.34 (m, 1 H), 7.49 (d, J = 4.41 Hz, 1 H), 7.54 (d, J = 8.09 Hz, 2 H), 7.70 (m, 1 H), 7.85 (m, 5 H), 8.09 (d, J = 8.46 Hz, 1 H), 8, 35 (d, J = 8.46 Hz, 1 H), 8.59 (d, J = 4.78 Hz, 1 H), 8.85 (d, J = 4.78 Hz, 1 H). Example 96 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (m, 12 H), 0.83 (t, J = 7.35 Hz, 3 H), 1.00 (m, 1 H), 1 , 26 (d, J = 2.94 Hz, 1 H), 1.39 (m, 1 H), 1.92 (s, 1 H), 2.68 (dd, J = 13.05, 3.49 Hz, 1 H), 2.79 (d, J = 9.56 Hz, 1 H), 2.87 (m, 2 H), 3.08 (t, J = 9.01 Hz, 1 H), 3.21 (m, 1 H), 3.35 (m, 2 H), 3.58 (s, 3 H), 3.64 (m, 2 H), 3.91 (d, J = 11.03 Hz, 1 H), 4.04 (m, 3 H), 4.57 (m, 2 H), 5.32 (d, J = 9.19 Hz, 2 H), 6.74 (d, J = 9.93 Hz, 1 H), 7.11 (m, 5 H), 7.36 (s, 1 H), 7.56 (d, J = 8.46 Hz, 2 H), 7.71 (m, 2 H), 7.84 (d, J = 8.46 Hz, 2 H), 7.97 (d, J = 8 , 09 Hz, 1 H), 8.28 (m, 1 H), 8.57 (d, J = 8.46 Hz, 1 H), 8.74 (dd, J = 5.52, 1.47 Hz, 1 H), 9.04 (d, J = 4.78 Hz, 1 H), 9.28 (d, J = 1.47 Hz, 1 H). Example 97 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (s, 9 H), 0.97 (s, 9 H), 2.54 (dd, J = 12.32, 2.76 Hz, 1 H), 2.75 (m, 1 H), 2.86 (m, 2 H), 3.11 (m, 2 H), 3.35 (m, 1 H), 3.48 (s, 3 H), 3.58 (t, J = 9.19 Hz, 2 H), 3.64 (s, 3 H), 3.79 (s, 3 H), 3.87 (m, 2 H), 4.02 (s, 1 H), 4.10 (m, 1 H), 4.50 (s, 2 H), 4.67 (s, 1 H), 4.71 (s, 2 H), 5.29 (d, J = 7.72 Hz, 1 H), 6.25 (d, J = 9.56 Hz, 1 H), 6.40 (s, 1 H), 6.84 (m, 2 H), 7.10 (m, 5 H), 7.21 (d, J = 8.46 Hz, 2 H), 7.26 (s, 1 H). Example 98 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (m, 15 H), 0.98 (m, 2 H), 1.32 (m, 1 H), 1.94 (m, 1 H ), 2.62 (dd, J = 12.13, 2.94 Hz, 2 H), 2.81 (m, 2 H), 2.92 (d, J = 7.72 Hz, 3 H), 3.14 (m, 3 H) , 3.61 (s, 3 H), 3.84 (m, 1 H), 4.15 (m, 1 H), 4.24 (d, J = 16.18 Hz, 1 H), 4.50 (d, J = 16.18 Hz, 1 H), 4.79 (s, 1 H), 5.28 (d, J = 9.19 Hz, 1 H), 6.50 (d, J = 9.56 Hz, 1 H), 6.66 (s, 1 H), 7.17 (m, 6 H), 7.37 (dd, J = 5.15, 2.21 Hz, 1 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H), 9.11 (s, 1 H), 9.15 (d, J = 5 , 15 Hz, 1 H). Example 99 1 H NMR (300 MHz, DMSO-d6) δ ppm 0.66 (m, 12 H), 0.74 (t, J = 7.17 Hz, 3 H), 0.88 (m, 1 H) , 1.05 (dd, J = 20.22, 6.62 Hz, 1 H), 1.28 (m, 2 H), 1.75 (s, 1 H), 2.68 (m, 5 H), 3.10 (m, 3 H), 3.50 (s, 3 H), 3.67 (d, J = 8.82 Hz, 2 H), 3.95 (m, 2 H), 4.03 (s, 1 H), 4.49 (m, 2 H), 4.93 (d, J = 2.94 Hz, 1 H), 6.93 (d, J = 9.56 Hz, 1 H), 7.10 (m, 3 H), 7.32 (m, 1 H), 7.43 (t, J = 8.64 Hz, 3 H), 7.86 (m, 2 H), 7.97 (m, 3 H), 8.65 (d, J = 4.41 Hz, 1 H), 9.12 (s, 1 H). Example 100 1 H NMR (300 MHz, CDCl 3) 8 ppm 0.82 (s, 9 H), 0.96 (s, 9 H), 1.39 (d, J = 6.99 Hz, 6 H), 1 , 80 (s, 5 H), 2.63 (s, 2 H), 2.86 (d, J = 7.35 Hz, 2 H), 3.14 (m, 2 H), 3.31 (m, 1 H), 3.63 (s, 3 H), 4.04 (s, 2 H), 4.12 (m, 1 H), 4.48 (t, J = 15.44 Hz, 2 H), 5.30 (s, 1 H), 6.33 (s, 1 H), 6.58 (s, 1 H), 7.00 (s, 1 H), 7.10 (m, 4 H), 7.22 (m, 1 H), 7.41 (d, J = 8.09 Hz, 2 H), 7.75 (m, 3 H), 7.96 (d, J = 8.09 Hz, 2 H), 8.69 (d, J = 4.41 Hz, 1 H). Example 101 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (d, J = 6.62 Hz, 3 H), 0.87 (t, J = 7.35 Hz, 3 H), 0.96 ( s, 9 H), 1.07 (m, 3 H), 1.43 (m, 1 H), 1.71 (s, 3 H), 1.91 (m, 1 H), 2.63 (m, 1 H), 2.90 (m, 2 H), 3.11 (m, 2 H), 3.15 (m, 2 H), 3.57 (d, J = 1.47 Hz, 1 H), 3.65 (s, 3 H), 3.76 (d, J = 9.19 Hz, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.06 (m, 2 H) 1 4.13 (d, J = 1.84 Hz, 1 H), 4.23 (m, 1 H), 4.46 (m, 2 H), 4.79 (s, 1 H), 5.39 (d, J = 9 , 93 Hz, 1 H), 6.52 (m, J = 7.72 Hz, 2 H), 7.03 (d, J = 7.72 Hz, 1 H), 7.07 (d, J = 7.35 Hz, 1 H), 7.15 (m, 5 H), 7.27 (s, 1 H), 7.54 (t, J = 7.72 Hz, 1 H), 7.97 (s, 1 H). Example 102 1 H NMR (300 MHz, CDCl 3) δ ppm 0.64 (d, J = 6.62 Hz, 3 H), 0.74 (t, J = 7.35 Hz, 3 H), 0.83 ( dd, J = 6.62, 2.21 Hz, 6 H), 0.92 (m, 1 H), 1.26 (d, J = 4.04 Hz, 1 H), 2.10 (m, 1 H), 2.62 (m, 1 H), 2.68 (s, 3 H), 2.80 (m, 1 H), 2.88 (m, 4 H), 3.12 (m, 1 H), 3.23 (m, 2 H), 3.59 (s, 3 H), 3.69 (m, 1 H), 3.79 (d, J = 10.66 Hz, 1 H), 3.97 (m, 2 H), 4.10 (d, J = 8.09 Hz, 1 H), 4.44 (m, 2 H), 5.07 (m, 1 H), 6.58 (d, J = 9.19 Hz, 1 H), 6.72 (s, 1 H), 6.97 (s, 1 H), 7.11 (m, 6 H), 7.22 (m, 1 H), 7.42 (d, J = 8.46 Hz, 2 H), 7.74 (m, 2 H), 7.94 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 103 1 H NMR (300 MHz, CDCl 3) δ ppm 0.65 (d, J = 6.62 Hz, 3 H), 0.74 (t, J = 7.17 Hz, 3 H), 0.85 ( m, 2 H), 0.96 (s, 9 H), 1.31 (m, 1 H), 1.65 (m, 1 H), 2.63 (d, J = 9.19 Hz, 1 H), 2.69 (d, J = 4.78 Hz, 3 H), 2.86 (m, 3 H), 3.14 (m, 1 H), 3.35 (m, 1 H), 3.60 (d, J = 6.25 Hz, 3 H), 3.68 (m, 2 H), 3.92 (d, J = 13.97 Hz, 1 H), 4.03 (m, 2 H), 4.11 (d, J = 8.46 Hz, 1 H), 4.46 (m, 2 H), 4.71 (s, 1 H), 5.10 (d, J = 7.72 Hz, 1 H), 6.31 (d, J = 9.56 Hz, 1 H), 6.61 (s, 1 H), 6.97 (d, J = 2.94 Hz, 1 H), 7.15 (m, 6 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.74 (m, 2 H) , 7.95 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 104 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (d, J = 6.62 Hz, 3 H), 0.87 (m, 3 H), 1.00 (s, 9 H), 1 , 07 (m, 2 H), 1.42 (m, 2 H), 1.91 (m, 1 H), 2.53 (s, 3 H), 2.64 (m, 2 H), 2.88 (m, 1 H), 3.15 (m, 2 H), 3.59 (d, J = 11.40 Hz, 1 H), 3.65 (s, 3 H), 3.81 (m, 1 H), 3.91 (m, 1 H), 4.09 (m, 2 H), 4.26 (m, 1 H), 4.47 (m, 2 H), 4.80 (s, 1 H), 5.40 (s, 1 H), 6.48 (d, J = 9.56 Hz, 1 H), 7.02 (d, J = 7.72 Hz, 1 H), 7.07 (d, J = 7.72 Hz, 2 H) , 7.16 (m, 5 H), 7.23 (s, 1 H), 7.35 (dd, J = 7.72, 4.78 Hz, 1 H), 7.53 (t, J = 7.54 Hz, 1 H), 7.84 (m, 1 H), 8.10 (d, J = 8.09 Hz, 1 H), 8.18 (s, 1 H), 8.63 (d, J = 4.04 Hz, 1 H). Example 105 1 H NMR (300 MHz, CDCl 3) δ ppm 0.70 (m, 6 H), 0.83 (dd, J = 6.62, 1.84 Hz, 6 H), 1.56 (s, 1 H), 1.84 (m, 1 H), 2.12 (m, 1 H), 2.61 (m, 1 H), 2.69 (m, 3 H), 2.81 (dd, J = 12.50, 10.30 Hz , 1 H), 2.91 (m, 2 H), 3.14 (m, 1 H), 3.24 (m, 1 H), 3.60 (s, 3 H), 3.66 (dd, J = 8.64, 6.80 Hz, 1 H), 3.91 (d, J = 13 , 60 Hz, 1 H), 4.02 (m, 1 H), 4.09 (d, J = 8.46 Hz, 1 H), 4.45 (m, 2 H), 4.74 (s, 1 H), 5.06 (s; 1 H), 6.59 (d, J = 8.82 Hz, 1 H), 6.73 (s, 1 H), 6.95 (d, J = 8.46 Hz,

1 H), 7.12 (m, 6 H), 7.21 (m, 2 H), 7.41 (d, J = 8.46 Hz, 1 H), 7.73 (m, 2 H) , 7.93 (t, J = 8.27 Hz, 3 H), 8.68 (d, J = 4.04 Hz, 1 H). Example 106 1 H NMR (300 MHz, CDCl 3) δ ppm 0.71 (t, J = 6.25 Hz, 6 H), 0.96 (d, J = 5.52 Hz, 9 H), 1.86 ( m, 1 H), 2.61 (dd, J = 12.13, 2.94 Hz, 1 H), 2.70 (m, 3 H), 2.80 (d, J = 10.30 Hz, 1 H), 2, 90 (m, 2 H), 3.16 (m, 1 H), 3.35 (m, 1 H), 3.64 (m, 2 H), 3.63 (m, 3 H), 3.92 (d, J = 13.60 Hz, 1 H), 4.05 (m, 2 H), 4.09 (m, 1 H), 4.47 (m, 2 H), 4.70 (s, 1 H), 5.09 (d, J = 9.56 Hz, 1 H), 6.32 (d, J = 9.56 Hz, 1 H), 6.61 (s, 1 H), 6.98 (s, 1 H), 7.11 (m, 6 H), 7.22 (m, 2 H), 7.41 (d, J = 8.09 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.04 Hz , 1 HOUR). Example 107 1 H NMR (300 MHz, CDCl 3) δ ppm 0.64 (d, J = 6.62 Hz, 3 H), 0.78 (m, 9 H), 0.96 (m, 2 H), 1 , 38 (m, 2 H), 1.90 (s, 1 H), 2.61 (m, 1 H), 2.66 (d, J = 11.77 Hz, 3 H), 2.86 (m, 3 H), 3.11 (m, 1 H), 3.23 (m, 2 H), 3.61 (m, 3 H), 3.70 (m, 1 H), 3.88 (d, J = 11.03 Hz, 1 H), 3.97 (d, J = 17.28 Hz, 1 H), 4.04 (s, 1 H), 4.44 (m, 2 H), 4.76 (s, 1 H), 5.12 (s, 1 H), 6.60 (s, 2 H), 6.79 (s, 2 H), 6.94 (d, J = 15.81 Hz, 1 H), 7.16 (m, 7 H), 7.42 (d, J = 8.46 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.68 (d, J = 4.04 Hz, 1 H). Example 108 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 15 H), 0.85 (m, 2 H), 0.97 (m, 1 H), 1.37 (m, 1 H ), 1.89 (s, 1 H), 2.61 (dd, J = 12.69, 3.49 Hz, 1 H), 2.69 (m, 3 H), 2.78 (d, J = 9.93 Hz, 1 H) , 2.87 (m, 2 H), 3.09 (m, 1 H), 3.23 (m, 1 H), 3.62 (m, 3 H), 3.64 (m, 2 H), 3.65 (m, 1 H), 3.88 (m, 1 H), 3.98 (d, J = 8.46 Hz, 1 H), 4.06 (m, 1 H), 4.44 (m, 2 H), 4.78 (s, 1 H), 5.25 (s, 1 H), 6.55 (d, J = 9.19 Hz, 1 H), 6.64 (s, 1 H), 6.96 (s, 1 H), 7.17 (m, 7 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.94 (d, J = 8.09 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 109 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 13.24 Hz, 9 H), 0.96 (m, 9 H), 2.61 (m, 2 H), 2 , 70 (s, 3 H), 2.79 (d, J = 10.66 Hz, 1 H), 2.88 (m, 2 H), 3.13 (m, 2 H), 3.34 (m, 1 H), 3.58 (s, 1 H), 3.63 (m, 3 H), 3.96 (m, 1 H), 4.04 (m, 2 H), 4.10 (m, 1 H), 4.46 (m, 2 H), 4.72 (s, 1 H), 5.28 (d, J = 9, 19 Hz, 1 H), 6.29 (d, J = 9.56 Hz, 1 H), 6.48 (s, 1 H), 6.97 (s, 1 H), 7.10 (m, 5 H), 7.21 (m, 2 H), 7.43 (d, J = 8.46 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 110 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (d, J = 6.62 Hz, 3 H), 0.81 (s, 9 H), 0.86 (m, 3 H), 1 , 01 (m, 1 H), 1.38 (m, 1 H), 1.91 (m, 1 H), 2.54 (dd, J = 12.32, 3.13 Hz, 1 H), 2.74 (m, 1 H) , 2.86 (t, J = 7.17 Hz, 2 H), 2.94 (m, 1 H), 3.10 (m, 1 H), 3.21 (m, 2 H), 3.47 (s, 2 H), 3.57 (m, 2 H), 3.62 (s, 3 H), 3.66 (s, 1 H), 3.78 (s, 3 H), 3.87 (m, 2 H), 4.06 (m, 1 H), 4.48 (s, 2 H), 4.69 (s, 2 H), 4.71 (s, 1 H), 5.27 (d, J = 8, 82 Hz, 1 H), 6.51 (m, 2 H), 6.83 (d, J = 8.46 Hz, 2 H), 7.12 (m, 6 H), 7.21 (d, J = 8.46 Hz, 2 H). Example 111 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 4.41 Hz, 3 H), 0.82 (s, 9 H), 0.87 (m, 3 H), 1 , 02 (m, 2 H), 1.37 (m, 1 H), 1.94 (m, 2 H), 2.55 (dd, J = 12.13, 2.94 Hz, 1 H), 2.76 (m, 1 H) , 2.88 (t, J = 6.99 Hz, 1 H), 3.57 (d, J = 9.93 Hz, 2 H), 3.63 (s, 3 H), 3.66 (d, J = 4.78 Hz, 2 H), 3.78 (s, 3 H), 3.89 ( d, J = 19.12 Hz, 1 H), 3.90 (s, 1 H), 3.95 (d, J = 5.15 Hz, 1 H), 4.07 (m, 1 H), 4.83 (m, 2 H), 5.29 (d, J = 8.82 Hz, 1 H) , 6.49 (m, 2 H), 6.84 (d, J = 8.82 Hz, 2 H), 7.07 (m, 6 H), 7.21 (d, J = 8.46 Hz, 2 H), 7.34 (d, J = 4.78 Hz, 1 H), 7.64 (t, J = 7.72 Hz, 1 H), 7.77 (m, 1 H), 8.21 (t, J = 9.01 Hz, 2 H), 8.93 (d, J = 4.41 Hz, 1 H). Example 112 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.66 (d, J = 6.62 Hz, 3 H), 0.73 (d, J = 6.62 Hz, 3 H), 0, 77 (d, J = 6.62 Hz, 3 H), 0.84 (t, J = 7.35 Hz, 3 H), 1.00 (m, 1 H), 1.37 (m, 2 H), 1.70 ( s, 1 H), 1.76 (s, 1 H), 1.87 (m, 2 H), 2.09 (m, 1 H), 2.24 (m, 1 H), 2.53 (s, 3 H), 2.72 (m, 1 H), 2.87 (m, 4 H), 3.13 (m, 4 H), 3.24 (m, 2 H), 3.76 (s, 1 H), 3.87 (d, J = 11.03 Hz, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.06 (d, J = 13.24 Hz, 1 H), 4.35 (m , J = 15.44 Hz, 2 H), 4.53 (m, 1 H), 7.12 (m, 4 H), 7.17 (s, 1 H), 7.22 (m, 3 H), 7.34 (m, 1 H), 7.53 (d, J = 8.46 Hz, 2 H), 7.69 (t, J = 7.72 Hz, 1 H), 7.84 (d, J = 7.72 Hz, 2 H), 7.91 (d, J = 8.46 Hz, 2 H), 8.60 (d, J = 4.41 Hz, 1 H) . Example 113 1 H NMR (300 MHz, CDCl 3) δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.78 (s, 9 H), 0.81 (m, 3 H), 0 , 96 (m, 1 H), 1.33 (m, 1 H), 1.95 (m, 4 H), 2.65 (dd, J = 12.50, 2.94 Hz, 1 H), 2.80 (m, 1 H) , 2.92 (m, 2 H), 3.15 (m, 2 H), 3.64 (m, 3 H), 3.65 (d, J = 9.56 Hz, 2 H), 3.83 (d, J = 11.03 Hz, 1 H), 4.00 (m, 2 H), 4.12 (c, J = 8.46 Hz, 1 H), 4.68 (m, 2 H), 5.36 (d, J = 9.19 Hz, 1 H), 6.63 (d, J = 9.56 Hz, 1 H), 7.15 (m, 6 H), 7.45 (d, J = 8.09 Hz, 2 H), 7.49 (m, 1 H), 7.59 (m, 1 H), 7.72 (d, J = 8.09 Hz, 1 H), 7.80 (m, 1 H), 7.92 (d, J = 8.09 Hz, 2 H), 8, 72 (d, J = 4.04 Hz, 1 H), 9.12 (dd, J = 4.78, 1.84 Hz, 1 H). Example 114 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.78 (s, 9 H), 0.91 (s, 9 H), 2.44 (d, J = 8.09 Hz, 1 H) , 2.66 (d, J = 3.31 Hz, 3 H), 2.78 (m, 2 H), 2.86 (m, 3 H), 3.11 (dd, J = 7.54, 2.39 Hz, 1 H), 3.35 (m, 2 H), 3.59 (s, 3 H), 3.72 (s, 1 H), 3.85 (d, J = 10.30 Hz, 1 H), 4.01 (d, J = 11.40 Hz, 2 H), 4.07 (m, 2 H), 4.16 (m, 1 H), 4.49 (d, J = 16.18 Hz, 1 H), 4.69 (m, 1 H), 7.09 (m, 3 H), 7.18 (m, 2 H), 7.35 (m, 1 H), 7.55 (m, 2 H), 7.82 (d, J = 8.09 Hz, 1 H), 7.88 (d, J = 8.46 Hz, 4 H), 7.92 (m, 2 H), 7.95 (m, 1 H), 8.59 (m, 1 H). Example 115 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.78 (s, 9 H), 0.91 (s, 9 H), 2.41 (d, J = 8.46 Hz, 1 H) , 2.41 (d, J = 8.46 Hz, 1 H), 2.83 (m, 4 H), 3.09 (t, J = 9.01 Hz, 1 H), 3.20 (t, J = 9.19 Hz, 1 H), 3.34 (s, 2 H), 3.59 (s, 3 H), 3.72 (s, 1 H), 3.83 (d, J = 1.47 Hz, 1 H), 3.97 (m, 3 H), 4.01 (d, J = 11.03 Hz, 1 H), 4, 03 (m, 3 H), 4.20 (d, J = 7.35 Hz, 1 H), 4.56 (m, 2 H), 7.11 (m, 3 H), 7.16 (m, 2 H), 7.35 (m, 1 H), 7.56 (m, 3 H), 7.87 (m, 4 H), 8.03 (m, 2 H), 8.60 (m, 1 H). Example 116 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.59 (d, J = 6.25 Hz, 3 H), 0.75 (d, J = 6.62 Hz, 3 H), 0, 83 (m, 6 H), 0.97 (m, 3 H), 1.34 (m, 3 H), 1.87 (m, 2 H), 2.52 (d, J = 5.88 Hz, 3 H), 2.66 (m, 1 H), 2.85 (m, 4 H), 3.09 (m, 4 H), 3.21 (m, 2 H), 3.34 (s, 1 H), 3.74 (m, 2 H), 3.89 (m, 2 H), 4.03 (m, 1 H), 4.34 (d, J = 75.81 Hz, 1 H), 4.54 (m, 1 H), 7.12 (m, 4 H), 7.21 (m, 3 H), 7.35 (m, 1 H), 7.54 (d, J = 8.46 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.85 (m, 3 H), 7.90 (d, J = 8.09 Hz, 2 H), 8.59 (d, J = 4.78 Hz, 1 H). Example 117 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.79 (s, 9 H), 0.92 (s, 9 H), 1.53 (d, J = 3.68 Hz, 6 H) , 2.33 (t, J = 8.82 Hz, 1 H), 2.69 (m, 2 H), 2.80 (m, 2 H), 2.84 (s, 1 H), 3.06 (m, 1 H), 3 , 21 (t, J = 9.19 Hz, 1 H), 3.27 (d, J = 2.57 Hz, 1 H), 3.33 (s, 1 H), 3.64 (s, 3 H), 3.72 (s, 1 H), 3.76 (s, 3 H), 3.81 ( d, J = 13.24 Hz, 2 H), 3.89 (m, 1 H), 4.05 (m, 1 H), 4.13 (m, 1 H), 4.41 (d, J = 15.44 Hz, 1 H), 4.59 (m, 1 H), 6.82 (m, 2 H), 7.08 (m, 3 H), 7.15 (d, J = 1.84 Hz, 1 H), 7.19 (m, 2 H), 7.28 (m, 2 H), 7.53 (d, J = 6.99 Hz, 1 H), 7.77 (t, J = 7.72 Hz, 1 H), 7.83 (s, 1 H). Example 118 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.72 (d, J = 6.62 Hz, 3 H), 0.79 (s, 9 H), 0.86 (t, J = 7 , 35 Hz, 3 H),

0.98 (m, 1 H), 1.39 (m, 1 H), 1.52 (d, J = 2.57 Hz, 6 H), 1.86 (m, 1 H), 2.65 (d, J = 15.44 Hz, 2 H), 2.74 (m, 1 H), 2.84 (m, 2 H), 3.07 (dd, J = 9.74, 4.60 Hz, 1 H), 3.13 (s, 1 H), 3.18 (m, 1 H), 3, 26 (d, J = 7.72 Hz, 1 H), 3.64 (s, 3 H), 3.71 (s, 1 H), 3.75 (s, 3 H), 3.79 (s, 1 H), 3.87 (m, 3 H), 4.16 (m, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.61 (d, J = 15.44 Hz, 1 H), 6.82 (m, 2 H), 7.09 (dd, J = 6.62, 4.04 Hz, 4 H), 7.16 (m, 4 H), 7.28 (m, 2 H), 7.52 (d, J = 6.99 Hz, 1 H), 7.75 (t, J = 7.91 Hz, 1 H). Example 119 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.79 (s, 9 H), 0.92 (s, 9 H), 2.39 (d, J = 9.56 Hz, 1 H) , 2.70 (m, 2 H), 2.83 (m, 2 H), 3.05 (m, 1 H), 3.16 (c, J = 9.07 Hz, 2 H), 3.65 (s, 3 H), 3.72 (s, 1 H), 3.76 (s, 3 H), 3.85 (m, 3 H), 4.05 (s, 1 H), 4.12 (m, 1 H), 4.47 (m, 2 H), 4.69 (s, 2 H), 6.82 (m, 2 H), 7.08 (m, 4 H), 7.15 (m, 3 H), 7.23 (d, J = 7.72 Hz, 1 H), 7.29 (m, 2 H), 7.45 (d, J = 7.35 Hz, 1 H), 7.84 (m, 2 H). Example 120 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.79 (s, 9 H), 0.92 (s, 9 H), 2.39 (d, J = 9.56 Hz, 1 H) , 2.70 (m, 2 H), 2.83 (m, 2 H), 3.05 (m, 1 H), 3.16 (c, J = 9.07 Hz, 2 H), 3.65 (s, 3 H), 3.72 (s, 1 H), 3.76 (s, 3 H), 3.85 (m, 3 H), 4.05 (s, 1 H), 4.12 (m, 1 H), 4.47 (m, 2 H), 4.69 (s, 2 H), 6.82 (m, 2 H), 7.08 (m, 4 H), 7.15 (m, 3 H), 7.23 (d, J = 7.72 Hz, 1 H), 7.29 (m, 2 H), 7.45 (d, J = 7.35 Hz, 1 H), 7.84 (m, 2 H). Example 121 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.72 (d, J = 6.62 Hz, 3 H), 0.79 (s, 9 H), 0.86 (t, J = 7 , 35 Hz, 3 H), 0.99 (m, 1 H), 1.37 (m, 1 H), 1.86 (s, 1 H), 2.66 (dd, J = 12.13, 3.31 Hz, 2 H) , 2.75 (m, 1 H), 2.83 (dd, J = 10.66, 4.04 Hz, 2 H), 3.13 (m, 3 H), 3.24 (d, J = 9.19 Hz, 1 H), 3.64 (s, 3 H), 3.72 (s, 1 H), 3.75 (s, 3 H), 3.79 (s, 1 H), 3.87 (m, 3 H), 3.91 (s, 1 H), 4.18 (m, 1 H), 4.36 (d, J = 15.81 Hz, 1 H), 4.57 (m, 1 H), 4.68 (s, 2 H), 6.82 (d, J = 8.82 Hz, 2 H), 7.14 (m, 6 H), 7.21 (d, J = 7.72 Hz, 1 H), 7.29 (d, J = 8.46 Hz, 2 H), 7.44 (d, J = 7.72 Hz, 1 H), 7.81 (t, J = 7.72 Hz, 1 H). Example 122 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (m, 12 H), 0.89 (m, 3 H), 1.04 (m, 2 H), 1.44 (m, 2 H ), 1.93 (d, J = 10.30 Hz, 1 H), 2.54 (m, 1 H), 2.76 (m, 2 H), 3.09 (m, 1 H), 3.22 (m, 1 H), 3.59 (m, 3 H), 3.78 (m, 3 H), 3.83 (m, 2 H), 3.93 (m, 1 H), 4.06 (m, 1 H), 4.77 (s, 1 H), 5.12 (m, 2 H), 5.28 (d, J = 8.82 Hz, 1 H), 6.59 (s, 2 H), 6.82 (d, J = 8.46 Hz, 2 H), 7.08 (m, 6 H), 7.19 (m, 2 H), 7.42 (m, 1 H), 7.53 (m, 1 H), 7.73 ( m, 2 H), 8.16 (dd, J = 8.46, 1.84 Hz, 1 H), 8.94 (dd, J = 4.04, 1.84 Hz, 1 H). Example 123 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (m, 12 H), 0.86 (t, J = 7.35 Hz, 3 H), 1.05 (m, 2 H), 1 , 36 (m, 2 H), 1.91 (m, 1 H), 2.53 (m, 1 H), 2.72 (d, J = 2.94 Hz, 3 H), 2.77 (d, J = 12.50 Hz, 1 H), 2.87 (m, 2 H), 3.03 (m, 2 H), 3.57 (d, J = 13.97 Hz, 2 H), 3.63 (s, 3 H), 3.79 (s, 3 H), 3.87 (d, J = 11.03 Hz, 1 H) , 3.94 (m, 1 H), 4.07 (m, 1 H), 4.74 (s, 1 H), 4.77 (d, J = 2.94 Hz, 2 H), 5.28 (d, J = 9.93 Hz, 1 H), 6.48 (m, 2 H), 6.84 (d, J = 8.82 Hz, 2 H), 7.06 (m, 3 H), 7.10 (m, 2 H), 7.17 (s, 1 H), 7.20 (m, 2 H), 7.52 (t, J = 6.99 Hz, 1 H), 7.67 (m, 1 H), 8.04 (d, J = 7.72 Hz, 1 H), 8.13 (d, J = 7.35 Hz, 1 H). Example 124 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 6.62 Hz, 3 H), 0.84 (m, 12 H), 0.99 (m, 2 H), 1 , 32 (m, 1 H), 1.94 (m, 1 H), 2.54 (dd, J = 11.95, 2.39 Hz, 1 H), 2.74 (m, 1 H), 2.87 (d, J = 7.35 Hz, 2 H), 3.07 (m, 1 H), 3.17 (m, 2 H), 3.57 (t, J = 9.01 Hz, 2 H), 3.64 (s, 3 H), 3.79 (m, 3 H), 3.89 (m, 3 H) , 3.88 (m, 2 H), 4.11 (m, 1 H), 4.60 (d, J = 15.44 Hz, 1 H), 4.71 (m, 1 H), 4.77 (m, 1 H), 5.28 (d, J = 9.19 Hz, 1 H), 6.39 ( m, 2 H), 6.83 (m, 2 H), 7.09 (m, 5 H), 7.22 (m, 2 H), 7.24 (s, 1 H), 7.99 (dd, J = 8.09, 1.47 Hz, 1 H), 8.38 (dd, J = 4 , 78, 1.47 Hz, 1 H). Example 125 1 H NMR (300 MHz, CDCl 3) δ ppm 0.76 (m, 3 H), 0.82 (s, 9 H), 0.86 (m, 3 H), 1.01 (m, 1 H ), 1.37 (m, 1 H), 1.94 (m, 1 H), 2.55 (dd, J = 12.32, 2.76 Hz, 1 H), 2.75 (m, 1 H), 2.89 (t, J = 7.54 Hz, 2 H), 3.15 (m, 1 H), 3.54 (s, 1 H), 3.60 (d, J = 9.56 Hz, 2 H), 3.63 (s, 3 H), 3.71 (d, J = 5.52 Hz, 1 H), 3.79 (s, 3 H), 3.86 (m, 3 H), 4.09 (m, 1 H), 4.70 (m, 3 H), 5.27 (d, J = 9.19 Hz, 1 H), 6.48 (m, 2 H), 6.84 (m, 2 H), 7.15 (m, 5 H), 7.20 (m, 2 H), 7.47 (m, 1 H), 7.57 (m, 1 H), 9.13 (dd, J = 4.78, 1.47 Hz, 1 H). Example 126 1 H NMR (300 MHz, CDCl 3) δ ppm 0.77 (m, 3 H), 0.82 (m, 12 H), 0.98 (m, 1 H), 1.37 (m, 1 H ), 1.87 (s, 1 H), 2.43 (s, 3 H), 2.60 (dd, J = 12.69, 3.49 Hz, 1 H), 2.82 (m, 2 H), 2.89 (t, J = 8.27 Hz, 1 H), 3.08 (m, 1 H), 3.59 (s, 3 H), 3.64 (d, J = 9.93 Hz, 2 H), 3.89 (d, J = 11.03 Hz, 1 H), 3.99 (d, J = 8.09 Hz, 2 H), 4.07 (m, 1 H), 4.44 (s, 2 H), 4.80 (s, 1 H), 5.25 (s, 1 H), 6.58 (d, J = 2.21 Hz, 2 H), 6.66 (s, 1 H), 6.73 (d, J = 3.31 Hz, 1 H), 7.12 (m, 6 H), 7.22 (m, 2 H), 7.44 (d, J = 8.09 Hz, 2 H), 7.74 (m, 3 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.69 (d, J = 4.78 Hz, 1 H). Example 127 1 H NMR (300 MHz, CDCl 3) δ ppm 0.63 (d, J = 6.99 Hz, 3 H), 0.78 (dd, J = 13.05, 6.80 Hz, 6 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.04 (m, 1 H), 1.30 (m, 1 H), 1.40 (dd, J = 10.85, 2.76 Hz, 1 H ), 1.63 (d, J = 4.04 Hz, 1 H), 1.92 (s, 1 H), 2.54 (s, 3 H), 2.59 (m, 1 H), 2.80 (dd, J = 12.32, 10.11 Hz, 1 H), 2.90 (d , J = 7.72 Hz, 2 H), 2.94 (s, 1 H), 3.14 (m, 2 H), 3.22 (m, 1 H), 3.57 (s, 1 H), 3.60 (s, 3 H), 3.68 (m, 1 H), 3.84 (d, J = 13.60 Hz, 1 H), 3.91 (d, J = 11.03 Hz, 1 H), 3.96 (m, 1 H), 4.08 (m, 1 H), 4.45 (m, 2 H), 4.75 (s, 1 H), 5.07 (s, 1 H), 6.59 (d, J = 18.75 Hz, 2 H), 7.09 (m, 4 H), 7.18 (m, 4 H), 7.29 (m, 4 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 128 1 H NMR (300 MHz, DMSO d6) δ ppm 0.64 (m, 3 H), 0.68 (s, 9 H), 0.74 (t, J = 7.35 Hz, 3 H), 0.92 (m, 1 H), 0.93 (m, 1 H), 1.24 (m, 2 H), 1.47 (m, 3 H), 1.54 (dd, J = 8.64, 6.07 Hz, 1 H), 1.74 (s, 1 H), 1.87 (s, 2 H), 2.50 (m, 3 H), 2.69 (m, 4 H), 3.12 (m, 3 H), 3.48 (d, J = 13.97 Hz, 3 H), 3.67 (d, J = 9 , 93 Hz, 2 H), 3.95 (m, 2 H), 4.04 (dd, J = 9.38, 6.43 Hz, 1 H), 4.35 (m, 2 H), 4.94 (d, J = 3.68 Hz, 1 H), 5.13 (m, 1 H), 6.95 (d, J = 9.93 Hz, 1 H), 7.07 (m, 5 H), 7.26 (s, 1 H), 7.35 (m, 1 H), 7.45 (d, J = 8.09 Hz, 2 H), 7.87 (m, 1 H), 7.99 (d, J = 8.09 Hz, 1 H), 8.63 (m, 1 H), 9.12 (s, 1 H). Example 129 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (m, 3 H), 0.88 (m, 3 H), 1.04 (m, 1 H), 1.25 (m, 2 H ), 1.32 (d, J = 6.25 Hz, 3 H), 1.42 (m, 2 H), 1.95 (m, 1 H), 2.52 (d, J = 5.15 Hz, 3 H), 2.87 ( m, 2 H), 2.96 (m, 2 H), 3.23 (m, 2 H), 3.63 (m, 2 H), 3.91 (d, J = 10.66 Hz, 1 H), 4.02 (m, 2 H), 4.20 (d, J = 8.09 Hz, 1 H), 4.45 (m, 2 H), 4.83 (s, 1 H), 6.51 (s, 1 H), 6.84 (d, J = 8.82 Hz, 1 H), 7.03 (m, 2 H), 7.18 (m, 4 H), 7.38 (d, J = 8.09 Hz, 2 H), 7.55 (m, 1 H), 7.73 (m, 3 H), 7.90 (d, J = 8.09 Hz, 2 H), 7.95 (m, 1 H), 8.66 (d, J = 4.78 Hz, 1 H). Example 130 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.88 (d, J = 6.62 Hz, 6 H), 0.99 (s, 9 H), 1.00 (s, 9 H) , 1.37 (c, J = 7.11 Hz, 2 H), 1.52 (s, 3H), 1.53 (s, 3 H), 1.66 (m, 1 H), 2.37 (d, J = 8.82 Hz , 1 H), 2.70 (m, 3 H), 2.74 (m, 1 H), 2.77 (d, J = 5.15 Hz, 1 H), 2.81 (t, J = 4.23 Hz, 1 H), 2.85 (s, 1 H), 2.87 (s, 1 H) , 3.07 (m, 2 H), 3.23 (m, 2 H), 3.66 (s, 3 H),

3.74 (s, 1 H), 3.84 (s, 1 H), 4.10 (s, 1 H), 4.13 (s, 1 H), 4.41 (d, J = 15, 44 Hz, 1 H), 4.60 (m, 1 H), 7.10 (m, 3 H), 7.15 (d, J = 1.47 Hz, 2 H), 7.19 (d, J = 7.72 Hz, 1 H), 7.53 (d, J = 6.99 Hz, 1 H), 7, 77 (t, J = 7.91 Hz, 1 H), 7.88 (d, J = 9.93 Hz, 1 H). Example 131 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.87 (m, 12 H), 1.00 (s, 9 H), 1.06 (m, 1 H), 1.40 (m, 4 H), 1.52 (d, J = 2.21 Hz, 6H), 1.64 (m, 1 H), 1.92 (m, 1 H), 2.67 (d, J = 6.62 Hz, 3 H), 2.75 (m, 3 H), 2.85 (m, 3 H), 3.13 (m, 4 H), 3.66 (s, 3 H), 3.73 (s, 1 H), 3.83 (s, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.14 (dd, J = 5.70, 3.86 Hz, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.62 (d, J = 15.81 Hz, 1 H), 7.10 (m, 3 H), 7.16 (m, 3 H), 7.52 ( d, J = 6.99 Hz, 1 H), 7.76 (t, J = 7.72 Hz, 1 H). Example 132 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.88 (d, J = 6.62 Hz, 6 H), 0.99 (s, 9 H), 1.01 (s, 9 H) 11.37 (c, J = 7.35 Hz, 2 H), 1.66 (m, 1 H), 2.41 (m, 1 H), 2.69 (m, 3 H), 2.76 (m, 2 H), 2 , 84 (m, 3 H), 3.05 (m, 2 H), 3.17 (c, J = 9.07 Hz, 1 H), 3.35 (m, 1 H), 3.66 (s, 3 H), 3.74 (s, 1 H), 3.84 (s, 1 H), 4 , 10 (s, 1 H), 4.13 (m, 1 H), 4.42 (d, J = 15.81 Hz, 1 H), 4.54 (m, 1 H), 4.70 (s, 2 H), 7.09 (m, 4 H), 7.17 (m, 2 H), 7.23 ( d, J = 7.35 Hz, 1 H), 7.45 (d, J = 7.72 Hz, 1 H), 7.83 (t, J = 7.72 Hz, 1 H). Example 133 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.85 (m, 6 H), 0.90 (m, 6 H), 1.00 (s, 9 H), 1.06 (m, 1 H), 1.39 (m, 4 H), 1.64 (m, 1 H), 1.91 (m, 1 H), 2.68 (m, 3 H), 2.74 (m, 2 H), 2.79 (m, 1 H), 2.85 (m, 2 H), 3.13 (m, 2 H), 3.18 (m, 1 H), 3.25 (m, 1 H), 3.66 (s, 3 H), 3.72 (d, J = 6.25 Hz, 1 H), 3.83 (s, 1 H), 3.94 (d, J = 11.40 Hz, 1 H), 4.15 (m, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.57 (m, 1 H), 4.69 (s, 2 H), 7.12 (m, 3 H), 7.17 (m, 3 H), 7.21 (d, J = 7.72 Hz, 1 H), 7.44 (d, J = 7.72 Hz, 1 H), 7.82 (t, J = 7.72 Hz, 1 H). Example 134 1 H NMR (300 MHz, DMSO d6) δ ppm 0.72 (dd, J = 6.43, 2.76 Hz, 3 H), 0.84 (m, 6 H), 1.20 (m, 5 H), 1.31 (m, 2 H), 1.83 (m, 1 H), 2.45 (m, 3 H), 2.64 (dd, J = 8.09, 3.68 Hz, 2 H) , 2.80 (m, 3 H), 3.14 (m, 2 H), 3.58 (m, 1 H), 4.03 (m, 3 H), 4.35 (s, 2 H), 4.84 (m, 1 H), 7.03 (d, J = 7.72 Hz, 1 H), 7.12 (m, 6 H), 7.21 (m, 1 H), 7.34 (m, 1 H), 7.46 (m, 3 H), 7.66 (m, 1 H), 7.88 (m, 2 H), 8.04 (m, 3 H), 8.65 (d, J = 4, 04 Hz, 1 H), 9.18 (d, J = 9.19 Hz, 1 H). Example 135 1 H NMR (300 MHz, CDCl 3), δ ppm 0.77 (d, J = 6.62 Hz, 3 H), 0.85 (m, 12 H), 0.97 (m, 1 H), 1.30 (m, 1 H), 1.89 (m, 1 H), 2.54 (d, J = 9.19 Hz, 2 H), 2.71 (d, J = 10.66 Hz, 1 H), 2.80 (m, 2 H), 3.01 (m, 2 H), 3.56 (dd, J = 17.46, 8.64 Hz, 2 H), 3.63 (s, 3 H), 3.79 (s, 3 H), 3.85 (m, 2 H), 3.94 (m, 1 H), 4.11 (d, J = 7.72 Hz, 1 H), 4.69 (m, 2 H), 4.88 (m, 1 H), 5.26 (m, 1 H), 6.33 (d, J = 9.93 Hz, 1 H), 6.39 (s, 1 H), 6.61 (m, 1 H), 6.72 (m, 1 H), 6.86 (m, 2 H), 6.92 (m, 2 H), 7.01 (m, 3 H), 7.22 (d, J = 8.46 Hz, 2 H), 7.37 (d, J = 6.99 Hz, 1 H), 7.42 (d, J = 8.82 Hz, 1 H), 8.32 (d, J = 7.35 Hz, 1 H). Example 136 1 H NMR (300 MHz, CF 3 COOD), δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.82 (t, J = 7.35 Hz, 3 H), 0.98 (m, 1 H), 1.35 (m, 1 H), 1.54 (m, 1 H), 1.86 (m, 1 H), 2.11 (m, 1 H), 2.18 (m, 3 H), 2.22 (m, 1 H), 2.52 (s, 3 H), 2.73 (m, 1 H), 2.80 (dd, J = 13.60, 2.21 Hz, 2 H), 2.89 (m, 2 H), 3.13 (m, 2 H), 3.25 (m, 1 H), 3.28 (m, 1 H), 3.33 (m, 1 H), 3.79 (m, 1 H), 3.90 (d, J = 11.03 Hz, 1 H), 3.97 (m, 1 H), 4.02 (d, J = 3.68 Hz, 2 H) , 4.24 (m, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.12 (m, 3 H), 7.18 (m, 3 H), 7.35 (m, 1 H), 7.54 (d, J = 8.46 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.85 (m, 2 H), 7.91 (m, 2 H), 8.60 (d, J = 4.41 Hz, 1 H). Example 137 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.41 (s, 2 H), 0.70 (s, 2 H), 0.82 (m, 6 H), 1.00 (s , 3 H), 1.33 (d, J = 25.37 Hz, 1 H), 1.88 (m, 1 H), 2.53 (s, 3 H), 2.73 (m, 1 H), 2.84 (d, J = 18, 75 Hz, 2 H), 3.11 (m, 2 H), 3.21 (m, 3 H), 3.34 (s, 3 H), 3.38 (m, 1 H), 3.91 (m, 2 H), 3.96 (m, 1 H), 4.27 (d, J = 12, 87 Hz, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.47 (d, J = 8.09 Hz, 1 H), 4.54 (d, J = 15.81 Hz, 1 H), 4.59 (s, 1 H), 4.68 (s, 1 H) , 7.13 (d, J = 7.35 Hz, 3 H), 7.19 (d, J = 7.72 Hz, 3 H), 7.35 (dd, J = 7.72, 5.52 Hz, 1 H), 7.58 (d, J = 7.72 Hz, 2 H), 7.73 (m, 1 H), 7.85 (m, 4 H), 8.59 (d, J = 5.15 Hz, 1 H). Example 138 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.50 (s, 1 H), 0.81 (s, 5 H), 0.86 (d, J = 7.35 Hz, 4 H ), 1.02 (d, J = 6.25 Hz, 2 H), 1.01 (s, 1 H), 1.38 (s, 2 H), 1.89 (s, 1 H), 2.45 (m, 3 H), 2 , 79 (m, 2 H), 3.20 (m, 3 H), 3.34 (s, 1 H), 3.79 (d, J = 18.38 Hz, 2 H) 1 3.88 (d, J = 11.40 Hz, 1 H), 4.37 (d, J = 32.36 Hz, 4 H), 4, 53 (m, 1 H), 4.73 (s, 1 H), 7.13 (d, J = 6.62 Hz, 4 H), 7.20 (m, 3 H), 7.36 (m, 1 H), 7.56 (d, J = 7.72 Hz, 3 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.86 (m, 5 H), 8.60 (d, J = 5.15 Hz, 1 H). Example 139 1 H NMR (300 MHz, CDCl 3), δ ppm 0.80 (m, 9 H), 0.97 (m, 9 H), 1.24 (t, J = 6.99 Hz, 1 H), 2.55 (s, 3 H), 2.62 (d, J = 9.56 Hz, 2 H), 2.80 (m, 1 H), 2.88 (m, 2 H), 3.13 (m, 2 H), 3.34 (s, 1 H), 3.60 (d, J = 10.30 Hz, 4 H), 3.97 (m, 2 H), 4.05 (m, 1 H), 4.13 (m, 1 H), 4.49 (s, 2 H), 4.74 (s, 1 H), 5.29 (m, 1 H), 6.31 (d, J = 9.56 Hz, 1 H), 6.46 (s, 1 H), 7.11 (m, 6 H), 7.23 (m, 1 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.58 (m, 1 H), 7.74 (m, 2 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.69 (d, J = 4.04 Hz, 1 H). Example 140 1 H NMR (300 MHz, DMSO d6), δ ppm 0.69 (m, 12 H), 0.79 (t, J = 7.35 Hz, 3 H), 0.95 (m, 1 H) , 1.28 (s, 1 H), 1.76 (s, 1 H), 2.69 (m, 4 H), 3.07 (m, 2 H), 3.37 (m, 3 H), 3.54 (s, 3 H), 3.70 (m, 8 H), 3.95 (d, J = 11.03 Hz, 2 H), 4.02 (s, 1 H), 4.17 (m, 3 H), 4.36 (m, 2 H), 6.73 (m, 2 H), 6.83 (s, 1 H), 6.95 (d, J = 9.19 Hz, 1 H), 7.07 (m, 5 H), 7.41 (d, J = 7.35 Hz, 2 H), 9.01 (s, 1 H). Example 141 1 H NMR (300 MHz, DMSO-d6), δ ppm 0.79 (m, 15 H), 0.94 (m, 9 H), 1.31 (m, 3 H), 1.77 (d , J = 11.40 Hz, 1 H), 2.63 (m, 6 H), 2.83 (m, 2 H), 3.09 (m, 3 H), 3.37 (s, 3 H), 3.57 ( m, 4 H), 3.78 (d, J = 9.19 Hz, 2 H), 4.00 (m, 5 H), 4.36 (m, 2 H), 7.07 (m, 5 H), 7.43 (m, 1 H), 8.98 (s, 1 H). Example 142 1 H NMR (300 MHz, CF 3 COOD), δ ppm 0.84 (m, 5 H), 1.01 (s, 1 H), 1.29 (s, 2 H), 1.76 (s, 1 H), 1.89 (s, 2 H), 2.06 (s, 1 H), 2.53 (s, 3 H), 2.70 (d, J = 8.82 Hz, 2 H), 2.85 (d, J = 6 , 25 Hz, 2 H), 2.99 (s, 1 H), 3.14 (m, 4 H), 3.45 (s, 1 H), 3.68 (s, 1 H), 3.83 (s, 2 H), 4.36 (m, 2 H), 4.54 (d, J = 15, 44 Hz, 2 H), 4.87 (s, 2 H), 7.12 (s, 3 H), 7.20 (t, J = 7.17 Hz, 3 H), 7.37 (d, J = 5.88 Hz, 1 H), 7.50 (s, 1 H), 7.55 (d, J = 8 , 09 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.87 (m, 4 H), 8.60 (d, J = 4.78 Hz, 1 H). Example 143 1 H NMR (300 MHz, BENZENE-d6), δ ppm 0.80 (m, 3 H), 0.85 (t, J = 7.35 Hz, 3 H), 1.01 (s, 1 H ), 1.29 (s, 3 H), 1.89 (s, 2 H), 2.05 (s, 1 H), 2.53 (s, 3 H), 2.70 (d, J = 9.93 Hz, 3 H) , 2.86 (s, 2 H), 2.99 (s, 1 H), 3.15 (m, 4 H), 3.49 (s, 1 H), 3.67 (s, 1 H), 3.88 (d, J = 11.03 Hz, 2 H), 4.34 (d, J = 15.81 Hz, 3 H), 4.53 (m, 1 H), 4.88 (s, 2 H), 7.13

(m, 3 H), 7.19 (m, 3 H), 7.36 (m, 1 H), 7.56 (s, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.88 (m, 3 H), 8.60 (d, J = 5.15 Hz, 1 H). Example 144 1 H NMR (300 MHz, CDCl 3), δ ppm 0.86 (m, 15 H), 0.94 (s, 1 H), 1.01 (m, 1 H), 1.13 (m, 6 H), 1.42 (m, 1 H), 1.93 (s, 1 H) 1 2.49 (d, J = 2.94 Hz, 1 H), 2.54 (s, 3 H), 2.74 (m, 1 H), 2.92 (m, 2 H), 3.15 (m, 3 H), 3.33 (m, 4 H), 3.52 (d, J = 9.93 Hz, 1 H), 3.62 (m, 4 H), 3.83 (m, 2 H), 3.92 (d, J = 11.40 Hz, 1 H), 4.06 (t, J = 8.27 Hz, 1 H), 4.46 (m, 2 H), 4.75 (s, 1 H), 5.31 (d, J = 9.19 Hz, 1 H), 6.43 (s, 1 H), 6.52 (d, J = 9.56 Hz, 1 H), 6.59 (d, J = 8.46 Hz, 2 H), 7.05 (m, 3 H), 7.11 (d, J = 2.21 Hz, 1 H), 7.17 (m, 4 H), 7.55 (m, 1 H). Example 145 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.75 (d, J = 6.62 Hz, 3 H), 0.83 (t, J = 7.35 Hz, 3 H), 0 , 87 (s, 9 H), 0.98 (dd, J = 15.63, 6.07 Hz, 1 H), 1.35 (s, 1 H), 1.84 (s, 1 H), 2.53 (s, 3 H) , 2.72 (m, 2 H), 2.81 (d, J = 6.99 Hz, 2 H), 2.88 (m, 2 H), 3.02 (s, 2 H), 3.17 (m, 7 H), 3.57 (s, 1 H), 3.82 (d, J = 15, 44 Hz, 1 H), 3.90 (m, 2 H), 4.04 (m, 1 H), 4.35 (d, J = 15.44 Hz, 2 H), 4.53 (m, 1 H), 4.91 (s, 2 H), 7.13 (m, 3 H), 7.19 (m, 3 H), 7.25 (m, 1 H), 7.53 (d, J = 8.46 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.85 (m, 2 H), 7.90 (d, J = 8.46 Hz, 2 H). Example 146 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.81 (s, 9 H), 0.93 (s, 9 H), 1.52 (s, 3 H), 1.53 (s , 3 H), 2.35 (d, J = 8.82 Hz, 1 H), 2.66 (dd, J = 12.69, 2.76 Hz, 1 H), 2.76 (m, 1 H), 2.82 (d, J = 3, 68 Hz, 2 H), 2.86 (m, 2 H), 3.06 (m, 1 H), 3.21 (t, J = 9.19 Hz, 1 H), 3.27 (d, J = 2.57 Hz, 1 H), 3.33 (s, 1 H), 3.65 (s, 2 H), 3.72 (s, 1 H), 3.80 (m, 2 H), 4.05 (s, 1 H), 4.12 (dd, J = 5.88, 4.04 Hz, 1 H), 4.19 (s, 4 H), 4.41 (d, J = 15.81 Hz , 1 H), 4.60 (m, 1 H), 4.91 (s, 2 H), 6.71 (d, J = 8.46 Hz, 1 H), 6.81 (m, 1 H), 6.89 (d, J = 1.84 Hz, 1 H), 7.09 (m, 2 H) , 7.15 (m, 2 H), 7.19 (d, J = 8.82 Hz, 1 H), 7.53 (d, J = 8.09 Hz, 1 H), 7.77 (t, J = 7.72 Hz, 1 H), 7.82 (d, J = 9.56 Hz, 1 H) . Example 147 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.80 (s, 9 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.01 (m, 1 H), 1.37 (m, 1 H), 1.88 (d, J = 8.09 Hz, 1 H), 2.64 (dd, J = 12.32, 3 , 13 Hz, 2 H), 2.71 (d, J = 6.62 Hz, 1 H), 2.77 (m, 1 H), 2.84 (m, 2 H), 3.12 (m, 2 H), 3.24 (m, 1 H), 3.65 (s, 3 H), 3.72 (s, 1 H), 3.78 (m, 3 H), 3.89 (m, 1 H), 4.16 (m, 1 H), 4.19 (s, 4 H), 4.36 (d, J = 15.44 Hz, 1 H), 4.57 (m, 1 H), 4.68 (s, 2 H), 4.91 (s, 2 H), 6.71 (d, J = 8.09 Hz, 1 H), 6.81 (m, 1 H), 6.89 (d, J = 2.21 Hz, 1 H), 7.11 (m, 3 H), 7.17 (m, 2 H), 7.21 (d, J = 7.72 Hz, 1 H), 7.44 (d, J = 7.72 Hz, 1 H), 7.81 (t, J = 7.72 Hz, 1 H), 7.84 (d, J = 10.30 Hz, 1 H). Example 148 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.81 (s, 9 H), 0.93 (s, 9 H), 2.39 (c, J = 9.80 Hz, 1 H ), 2.66 (m, 1 H), 2.75 (d, J = 9.93 Hz, 1 H), 2.82 (d, J = 2.94 Hz, 1 H), 2.86 (m, 1 H), 3.05 (m, 2 H), 3.16 (c, J = 9.07 Hz, 2 H), 3.34 (s, 1 H), 3.65 (s, 3 H), 3.72 (s, 1 H), 3.80 (m, 3 H), 4.05 (s, 1 H), 4.13 (m, 1 H), 4.19 (s, 4 H), 4.41 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 4.69 (s, 2 H), 4.91 (s, 1 H), 6.71 (d, J = 8.09 Hz, 1 H), 6.81 (m, 1 H), 6.89 (d, J = 2.21 Hz, 1 H), 7.08 (m, 2 H), 7.16 (m, 2 H), 7.23 (d, J = 7.72 Hz, 1 H), 7.45 (d, J = 7.35 Hz, 1 H) , 7.83 (m, 2 H). Example 149 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.80 (s, 9 H), 0.86 (t, J = 7.35 Hz, 3 H), 1.01 (m, 1 H), 1.39 (m, 1 H), 1.84 (m, 1 H), 2.64 (m, 4 H), 2.75 (m, 1 H), 2.83 (m, 3 H), 3.14 (m, 2 H), 3.27 (d, J = 7.72 Hz, 1 H), 3.65 (s, 3 H), 3.72 (s, 1 H), 3.75 (s, 1 H), 3.80 (d, J = 4.04 Hz, 2 H), 3.88 (d, J = 11.40 Hz, 1 H), 4.16 (d, J = 5.52 Hz, 1 H), 4.18 (d, J = 7.35 Hz, 4 H), 4.37 (d, J = 15.81 Hz, 1 H), 4, 61 (d, J = 15.81 Hz, 1 H), 4.91 (s, 2 H), 6.71 (d, J = 8.09 Hz, 1 H), 6.81 (m, 1 H), 6.89 (d, J = 1.84 Hz, 1 H), 7.10 (m, 2 H), 7.16 (m, 3 H), 7.52 (d, J = 8.09 Hz, 1 H), 7.76 (t, J = 7.91 Hz, 1 H), 7.82 (s, 1 H). Example 150 1 H NMR (300 MHz, DMSO d6), δ ppm 0.71 (dd, J = 5.15, 2.94 Hz, 6 H), 0.79 (m, 3 H), 0.86 (t , J = 7.91 Hz, 1 H), 0.93 (dd, J = 17.46, 8.27 Hz, 3 H), 1.15 (m, 1 H), 1.22 (m, 2 H), 1.80 (s, 1 H), 2.45 (s, 2 H), 2.54 (s, 1 H), 2.76 (d, J = 30.89 Hz, 3 H), 2.96 (d, J = 2.94 Hz, 1 H), 3.14 (m, 3 H), 3.32 (s, 2 H), 3.64 (s, 1 H), 3.96 (m, 4 H), 4.34 (d, J = 11.03 Hz, 2 H), 4.82 (t, J = 4.04 Hz, 1 H), 7.03 (d, J = 7.35 Hz, 1 H), 7, 17 (m, 5 H), 7.35 (m, 2 H), 7.45 (m, 2 H), 7.65 (t, J = 7.72 Hz, 1 H), 7.87 (d, J = 6.99 Hz, 1 H), 7.93 (m, 1 H), 8.02 (d, J = 8.09 Hz, 2 H), 8.65 (d, J = 4.78 Hz, 1 H), 9.28 (d, J = 15.08 Hz, 1 H). Example 151 1 H NMR (300 MHz, CDCl 3), δ ppm 0.75 (m, 9 H), 0.94 (m, 10 H), 2.38 (s, 3 H), 2.58 (m, 1 H), 2.78 (m, 1 H), 2.88 (t, J = 8.46 Hz, 2 H), 2.96 (m, 1 H), 3.31 (m, 1 H), 3.58 (d, J = 9, 19 Hz, 2 H), 3.64 (s, 3 H), 3.88 (d, J = 13.97 Hz, 1 H), 4.00 (t, J = 6.99 Hz, 2 H), 4.13 (d, J = 8.82 Hz, 1 H), 4.30 (d, J = 15, 08 Hz, 1 H), 4.50 (m, 1 H), 4.71 (s, 1 H), 5.29 (d, J = 9.56 Hz, 1 H), 6.28 (d, J = 9.56 Hz, 1 H), 6.44 (s, 1 H), 7.05 (m, 3 H), 7.15 (m, 3 H), 7.30 (m, 5 H), 8.39 (s, 1 H), 8.43 (d, J = 4.78 Hz, 1 H). Example 152 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.89 (s, 6 H), 0.99 (s, 9 H), 1.01 (s, 9 H), 1.24 (t , J = 7.17 Hz, 1 H), 1.43 (t, J = 8.27 Hz, 3 H), 1.53 (d, J = 3.68 Hz, 6 H), 2.37 (d, J = 8.82 Hz, 1 H), 2.68 (m, 2 H), 2.76 (m, 2 H), 2.83 (m, 2 H), 3.07 (m, 1 H), 3.23 (dd, J = 18.20, 8.64 Hz, 2 H), 3.34 (m, 1 H), 3, 66 (s, 3 H), 3.73 (m, 1 H), 3.84 (s, 1 H), 4.11 (m, 2 H), 4.13 (s, 1 H), 4.41 (d, J = 15.81 Hz, 1 H), 4.60 (m, 1 H), 4.91 (s, 2 H), 7.08 (m, 2 H), 7.16 (m, 2 H), 7.21 (s, 1 H), 7.53 (d, J = 6.99 Hz, 1 H), 7.77 (t, J = 7.72 Hz, 1 H), 7.88 (d, J = 9 , 56 Hz, 1 H). Example 153 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.87 (m, 21 H), 1.00 (s, 9 H), 1.06 (m, 1 H), 1.41 (m , 2 H), 1.89 (s, 1 H), 2.67 (m, 4 H), 2.74 (m, 4 H), 2.85 (m, 2 H), 3.15 (m, 2 H), 3.26 (s, 1 H), 3.27 (s, 1 H), 3.66 (s, 3 H), 3.72 (t, J = 6.07 Hz, 1 H), 3.83 (s, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.12 (m, 1 H), 4.37 ( d, J = 15.81 Hz, 1 H), 4.62 (d, J = 15.81 Hz, 1 H), 7.10 (m, 2 H), 7.17 (m, 3 H), 7.52 (d, J = 8.09 Hz, 1 H), 7.76 (t, J = 7.91 Hz, 1 H), 7.85 (d, J = 9.56 Hz, 1 H). Example 154 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.89 (s, 6 H), 0.99 (s, 9 H), 1.01 (s, 9 H), 1.43 (t , J = 8.27 Hz, 2 H), 2.42 (d, J = 9.56 Hz, 1H), 2.68 (m, 3H), 2.76 (m, 2H), 2.82 (m, 2 H), 3.05 (m, 1 H), 3.17 (c, J = 9.19 Hz, 2 H), 3.34 (d, J = 2.94 Hz, 2 H), 3.66 (s, 3 H), 3.74 (t, J = 6.43 Hz, 1 H), 3.84 (s, 1 H) , 4.10 (d, J = 6.62 Hz, 2 H), 4.42 (d, J = 15.81 Hz, 1 H), 4.54 (m, 1 H), 4.70 (s, 2 H), 4.91 (s, 1 H), 7.10 (c, J = 5.52 Hz, 3 H), 7.17 (m, 3 H), 7.23 (d, J = 7.72 Hz, 1 H), 7.45 (d, J = 7.72 Hz, 1 H), 7.84 (t, J = 7.72 Hz, 1 H), 7.89 (d, J = 9, 19 Hz, 1 H). Example 155 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.85 (d, J = 6.62 Hz, 3 H), 0.90 (m, 12 H), 0.98 (d, J = 11.77 Hz, 9 H), 1.04 (d, J = 1.47 Hz, 1 H), 1.42 (m, 3 H), 1.87 (d, J = 10.66 Hz, 1 H), 2.69 (m, 2 H), 2.77 (m, 3 H), 2.85 (m, 2 H), 3.12 (m, 2 H), 3.24 (m, 2 H), 3.66 (s, 3 H), 3.73 (m, 1 H), 3.84 (s, 1 H), 3.94 (d, J = 11.40 Hz, 1 H), 4.15 (d, J = 1.84 Hz, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.57 (m, 1 H), 4.69 (s, 2 H), 4.87 (s, 2 H), 7.12 (m, 3 H), 7.17 (m, 2 H), 7.22 (d, J = 7.72 Hz, 1 H), 7.44 (d, J = 7.35 Hz, 1 H), 7.82 (t, J = 7.72 Hz, 1 H).

Example 156 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.13 (m, 2 H), 0.46 (m, 2 H), 0.91 (s, 1 H), 0.99 (s , 9 H), 1.00 (s, 9 H), 1.52 (s, 3 H), 1.53 (s, 3 H), 2.41 (d, J = 9.19 Hz, 1 H), 2.53 (dd, J = 12, 87, 6.62 Hz, 1 H), 2.70 (m, 1 H), 2.75 (m, 2 H), 2.84 (m, 3 H), 3.08 (m, 1 H), 3.24 (m, 2 H), 3.34 (m, 1 H), 3.66 (s, 3 H), 3.76 (s, 1 H), 3.87 (s, 1 H), 4.10 (s, 1 H), 4.14 (m, 1 H), 4.41 (d, J = 15.44 Hz, 1 H), 4.60 (m, 1 H), 7.09 (m, 3 H), 7.16 (m, 2 H), 7.20 (s, 1 H), 7.53 (d, J = 6.99 Hz, 1 H), 7.77 (t, J = 7.91 Hz, 1 H), 7.86 (d, J = 9.19 Hz, 1 H). Example 157 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.14 (m, 2 H), 0.46 (m, 2 H), 0.84 (d, J = 6.25 Hz, 3 H ), 0.90 (m, 6 H), 0.99 (s, 9 H), 1.05 (m, 1 H), 1.41 (m, 1 H), 1.52 (d, J = 2.57 Hz, 6 H), 1.89 (s, 1 H), 2.52 (dd, J = 12.87, 6.99 Hz, 1 H), 2.71 (m, 3 H), 2.86 (m, 2 H), 3.14 (m, 3 H), 3.26 (d, J = 3.31 Hz, 1 H), 3.66 (s, 3 H), 3.76 (s, 1 H), 3.87 (s, 1 H), 3.93 (d, J = 11.40 Hz, 1 H), 4.17 (m, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.61 (d, J = 15.81 Hz, 1 H), 4.91 (s, 1 H), 7.11 (m, 2H), 7.17 (m, 3 H), 7.52 (d, J = 6.99 Hz, 1 H), 7.76 (t, J = 7.72 Hz, 1 H), 7.83 (d, J = 9.19 Hz, 1 H). Example 158 1 H NMR (300 MHz, MeOH-d4), δ ppm 0.15 (m, 2 H), 0.47 (m, 2 H), 0.90 (m, 1 H), 0.99 (s , 9 H), 1.00 (s, 9 H), 2.45 (d, J = 9.56 Hz, 1 H), 2.53 (dd, J = 12.69, 6.80 Hz, 2 H), 2.69 (m, 1 H ), 2.75 (m, 2 H), 2.84 (m, 2 H), 3.06 (m, 2H), 3.18 (c, J = 9.07 Hz, 1 H), 3.36 (m, 1 H), 3.66 (s, 3 H), 3.76 (s, 1 H), 3.87 (s, 1 H), 4.11 (s, 1 H), 4.14 (m, 1 H), 4.42 (d, J = 15.44 Hz, 1 H), 4.54 (m, 1 H), 4.69 (s, 2 H), 7.10 (m, 3 H), 7.16 (m, 2 H), 7.23 (d, J = 7.72 Hz, 1 H), 7.45 (d, J = 7.72 Hz, 1 H), 7.85 (m, 2 H). Example 159 1H NMR (300 MHz, MeOH-d4), δ ppm 0.84 (d, J = 6.62 Hz, 3 H), 0.89 (m, 3 H), 0.97 (s, 1H) , 0.98 (d, J = 6.62 Hz, 9 H) 1 1.06 (m, 1 H), 1.40 (m, 1 H), 1.89 (m, 1 H), 2.52 (dd, J = 12.69 , 6.80 Hz, 1 H), 2.73 (m, 4 H), 2.81 (m, 1 H), 2.88 (m, 2 H), 3.13 (m, 4 H), 3.24 (t, J = 9.01 Hz, 3 H), 3.66 (s, 3 H), 3.77 (s, 1 H), 3.87 (s, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.17 (m, 1 H), 4.37 (d, J = 15.81 Hz, 1 H), 4.57 (m, 1 H), 4.69 (s, 2 H), 4.91 (s, 1 H), 4.91 (s, 1 H), 7.12 (m, 3 H), 7.17 (m, 2 H), 7.21 (d, J = 8.09 Hz, 1 H), 7.44 (d, J = 7.72 Hz, 1 H), 7, 82 (t, J = 7.72 Hz, 1 H), 7.87 (d, J = 8.46 Hz, 1 H). Example 160 1 H NMR (300 MHz, CDCl 3), δ ppm 0.63 (d, J = 6.62 Hz, 3 H), 0.92 (m, 14 H), 1.35 (m, 3 H), 1.92 (m, 1 H), 2.59 (dd, J = 12.32, 3.13 Hz, 1 H), 2.69 (s, 3H), 2.84 (m, 3H), 3.10 (m, 1 H ), 3.22 (m, 2H), 3.64 (m, 3 H), 3.95 (m, 4 H), 4.43 (m, 2H), 4.74 (s, 1 H), 5.11 (d, J = 8.09 Hz, 1 H), 6.58 (d, J = 9, 56 Hz, 1 H), 6.68 (s, 1 H), 6.97 (s, 1 H), 7.18 (m, 5H), 7.30 (m, 5 H). Example 161 1 H NMR (300 MHz, CDCl 3), δ ppm 0.79 (d, J = 6.25 Hz, 3 H), 0.82 (s, 9 H), 0.87 (t, J = 7, 35 Hz, 3 H), 1.04 (m, 1 H), 1.38 (m, 1 H), 1.93 (m, 1 H), 2.58 (dd, J = 12.50, 2.94 Hz, 1 H) , 2.77 (m, 1 H), 2.91 (m, 4 H), 3.09 (m, 3 H), 3.60 (m, 1 H), 3.62 (s, 3 H), 3.78 (s, 3 H), 3.88 (m, 2 H), 4.10 (m, 1 H), 4.45 (d, J = 15.08 Hz, 1 H), 4.67 (d, J = 15.08 Hz, 1 H), 5.30 (da, J = 7.54 Hz, 1 H), 6.59 (da, J = 9.56 Hz, 1 H), 6.64 (sa, 1 H), 6.83 (d, J = 8.82 Hz, 2 H), 7.08-7.22 (m, 7 H), 7.54 (m, 1 H), 7.71 (m, 1 H), 7.80 (m, 1 H), 8.06 (d, J = 1.84 Hz, 1 H), 8.09 (d, J = 8.46 Hz, 1 H), 8.85 (d, J = 2.21 Hz, 1 H). Example 162 1 H NMR (300 MHz, CDCl 3), δ ppm 0.80-0.82 (m, 12 H), 0.88 (t, J = 7.35 Hz, 3 H), 1.05 (m, 1 H), 1.44 (m, 1 H), 1.95 (m, 1 H), 2.55 (dd, J = 12.32, 3.13 Hz, 1 H), 2.77 (m, 1 H), 2, 93 (m, 4 H), 3.16 (m, 3 H), 3.60 (m, 1 H), 3.62 (s, 3 H), 3.78 (s, 3 H), 3.86 (d, J = 8.46 Hz, 1 H), 3.94 (d, J = 11.40 Hz, 1 H), 4.09 (m, 1 H), 4.64 (d, J = 15.44 Hz, 1 H), 4.73 (d, J = 15.44 Hz, 1 H), 5.29 (da, J = 9.19 Hz, 1 H), 6.51 (sa, 1 H), 6.58 (da, J = 9.56 Hz, 1 H), 6.82 (d, J = 8.82 Hz, 2 H), 7.10-7.21 (m, 7H), 7.44 (d, J = 8.46 Hz, 1 H), 7.54 (m, 1 H), 7.71 (m, 1 H), 7.80 (m, 1 H), 8.06 (d a, J = 8.46 Hz, 1 H), 8.14 (d, J = 8.09 Hz, 1 H). Example 165 1 H NMR (300 MHz, CDCl 3), δ ppm 0.80 (m, 9 H), 0.96 (d, J = 13.97 Hz, 9 H), 1.62 (s, 3 H), 2.60 (m, 1 H), 2.83 (m, 4 H), 3.10 (m, 2 H), 3.34 (s, 1 H), 3.60 (m, 4 H), 3.98 (m, 4 H), 4.49 (d, J = 2.57 Hz, 3 H), 4.71 (s, 1 H), 5.29 (d, J = 9.19 Hz, 1 H), 6.28 (d, J = 9.56 Hz, 1 H), 6.40 (s, 1 H), 7.10 (m, 7 H), 7.28 (m, 5 H), 7.56 (t, J = 7.72 Hz, 1 H). Example 166 1 H NMR (300 MHz, CDCl 3) δ ppm 0.90-0.82 (m, 6H), 0.99 (s, 9H), 1.07-0.96 (m, 1H), 1.45 -1.39 (m, 1 H), 2.00-1.86 (m, 1H), 2.54 (s, 3H), 2.69-2.61 (m, 2H), 2.90-2.87 (m, 3H), 3, 23-3.08 (m, 3H), 3.66-3.54 (m, 1H), 3.63 (s, 3H), 3.79-3.76 (m, 1H), 3.95-3.92 (d, J = 11.03, 1H), 4.16-4.03 (m, 1H), 4, 28-4.07 (dd, J = 48.9, 15.44 Hz, 2H), 4,494.47 (m, 2H), 4.82 (s, 1H), 5.40-5.37 (m, 1H), 6.53-6.49 (d, J = 9.56.1H), 7.18-7.02 (m, 6H), 7.23 (s, 1H), 7.44-7, 40 (m, 1H), 7.54 (t, J = 7.72, 1H), 8.20-8.15 (m, 2H), 8.70-8.68 (m, 1H), 9.14 (d, J = 1.84 Hz, 1H). Example 167 1 H NMR (300 MHz, DMSO d6) δ ppm 0.65 (s, 9H), 0.70-0.65 (m, 3H), 0.81-0.77 (m, 3H), 0, 88-0.84 (m, 2H), 0.98-0.94 (m, 1H), 1.77 (m, 1H), 2.79-2.62 (m, 4H), 3.08-2.99 (m, 1H) , 3.25-3.16 (m, 2H), 3.53 (s, 3H), 3.67-3.55 (m, 2H), 3.98-3.84 (m, 2H), 3.99-3.96 (d, J = 10.67 Hz, 1H), 4.05 (m, 1H), 4, 54-4.41 (dd, J = 15.81.21.7 Hz, 2H), 4.93-4.92 (d, J = 3.31 Hz, 1H), 6.96-6.93 (d, J = 9.56 Hz, 1H), 7.01-7.10 (m, 5H), 7.28-7.19 (m, 3H), 7.35-7.32 (m, 2H), 7.45-7.42 (d, J = 9.56 Hz, 1H) 7.54-7.50 (dd, J = 8.82, 4.78 Hz, 1H) 7.60 (s , 1H) 8.30-8.26 (ddd, J = 8.27, 2.02, 1.84 Hz, 1H) 8.67-8.64 (dd, J = 4.78, 1.47 Hz, 1H) 9.06 (s, 1H) 9.13-9.12 (d, J = 1.47 Hz, 1H). Example 168 1 H NMR (300 MHz, CD 3 OD), δ ppm 0.83 (m, 6 H), 0.89 (s, 9 H), 0.97 (m, 1 H), 1.01 (s, 9 H), 1.30 (m, 1 H), 1.42 (t, J = 8.27 Hz, 2 H), 1.86 (m, 1 H), 2.44 (m, 1 H), 2.65-2.84 (m, 6 H), 3.04 (m, 3 H), 3.65 (s, 3 H), 3.72 (m, 1 H), 3.83 (s, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.14 (m, 1 H), 4.73 (d, J = 15, 44 Hz, 1 H), 4.86 (d, J = 15.44 Hz, 1 H), 6.74 (m, 1 H), 6.83 (m, 3 H), 6.94 (ta, J = 7.35 Hz, 1 H), 7.01 (m, 2 H), 7.41 (sa, 1 H), 7.56 (m, 1 H), 8.36 (da, J = 7.35 Hz, 1 H). Example 169 1 H NMR (300 MHz, CD 3 OD), δ ppm 0.89 (s, 9 H), 0.95 (s, 9 H), 1.01 (s, 9 H), 1.43 (t, J = 8.27 Hz, 2 H), 2.05 (m, 1 H), 2.66-2.81 (m, 6 H), 2.96 (m, 2 H), 3.20 (m, 1 H), 3.65 (s, 3 H), 3.73 (m, 1 H), 3.84 (sa, 1 H), 4.08 (sa, 1 H), 4.11 (m, 1 H), 4.64 (d, J = 15.81 Hz, 1 H), 4.95 (d, J = 15.81 Hz, 1 H), 6, 69 (t, J = 7.54 Hz, 2 H), 6.76 (m, 1 H), 6.86 (m, 2 H), 6.98 (da, J = 7.35 Hz, 2 H), 7.43 (sa, 1 H), 7.58 (m, 1 H), 7.83 (da, J = 9.93 Hz, 1 H), 8.38 (da, J = 6.99 Hz, 1 H). Example 170 1 H NMR (300 MHz, CDCl 3), δ ppm 0.84 (s, 9 H), 0.93 (s, 9 H), 2.14 (m, 1 H), 2.55 (dd, J = 12.50, 2.21 Hz, 1 H), 2.74 (m, 4 H), 2.97 (m, 2 H), 3.18 (m, 1 H), 3.59 (da, J = 9.19 Hz, 2 H), 3.63 (s, 3 H), 3.80 (s, 3 H), 3.84 (d, J = 113.60 Hz, 1 H), 3.94 (d, J = 13.60 Hz, 1 H), 4.12 (m, 1 H), 4.62 (d, J = 15.44 Hz , 1 H), 4.69 (s, 1 H), 4.99 (d, J =

15.44 Hz, 1 H), 5.28 (da, J = 9.56 Hz, 1 H), 6.10 (da, J = 9.56 Hz, 1 H), 6.32 (sa, 1 H), 6.65 (m, 1 H), 6.75 (m, 3 H), 6.89 (m, 5 H), 7.22 (d, J = 8.82 Hz, 2 H), 7.40 (sa, 1 H), 7.45 (m, 1 H), 8.35 (m, 1 H). Example 171 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (s, 9H), 0.90-0.83 (m, 6H), 1.02 (s, 9H), 1.11-1.00 (m, 1H), 1,421.35 (m, 2H), 1.99-1.89 (m, 1H), 2.58-2.53 (m, 1H), 2.78-2.64 (m , 4H), 3.14-2.28 (m, 4H), 3.61 (s, 3H), 3.77-3.59 (m, 3H), 4.09-3.96 (m, 2H), 4.73 (sa, 1H), 4.82 (s, 2H), 5.37-5.34 (m, 1H), 6.64 -6.61 (m, 1H), 6.71 (sa, 1H), 7.13-7.05 (m, 5H), 7.30-7.28 (d, J = 4.41 Hz, 1H), 7.63-7.57 (t, J = 6.99 Hz, 1H), 7.76- 7.70 (t, J = 6.99 Hz, 1H), 8.15-8.12 (d, J = 8.45 Hz, 1H), 8.21 -8.18 (d, J = 8.45 Hz, 1H), 8.89-8.88 (d, J = 4.42 Hz, 1H). Example 172 1 H NMR (300 MHz, CDCl 3), δ ppm 0.67 (d, J = 6.99 Hz, 3 H), 0.93 (m, 11 H), 1.39 (m, 2 H), 1.61 (m, 1 H), 1.90 (s, 1 H), 2.54 (dd, J = 12.32, 3.13 Hz, 1 H), 2.81 (m, 8 H), 3.10 (m, 1 H), 3.22 (m, 2 H), 3.77 (m, 11 H), 4.08 (d, J = 8.09 Hz, 1 H), 4.44 (m, 2 H), 4.70 (s, 1 H), 5.08 (s, 1 H), 6.56 (m, 2 H), 6.85 (m, 2 H), 6.97 (s, 1 H), 7.14 (m, 6 H). Example 173 1H NMR (300 MHz, CDCl3) δ ppm 0.64-0.62 (d, J = 6.61 Hz, 3H), 0.89-0.75 (m, 12H), 1.10-0 , 93 (m, 1 H), 1.99-1.89 (m, 1H), 2.61-2.56 (m, 1H), 2.89-2.76 (m, 4H), 3.10-2.98 (m, 3H ), 3.70-3.57 (m, 2H), 3.62 (s, 3H), 4.01-3.83 (m, 3H), 4.16-4.06 (m, 1H), 4.89-4.74 (dd, J = 15.44, 29.05 Hz, 2H), 4.76 (sa, 1H ), 5.10-5.08 (m, 1H), 6.54-6.51 (d, J = 9.2 Hz, 1H), 6.59 (sa, 1 H), 7.12-7.04 (m, 5H) 7.31-7.28 (m, 6H), 7.63-7, 58 (ddd, J = 8.27, 6.99.1.29 Hz, 1H), 7.757.70 (ddd, J = 8.36, 6.89, 1.29 Hz, 1H), 8.15- 8.12 (d, J = 8.46, 1H) 8.22-8.19 (d, J = 8.45, 1H) 8.88-8.87 (d, J = 4.41 Hz, 1H). Example 174 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (s, 9H), 0.89-0.83 (m, 6H), 1.01 (s, 9H), 1.12-0.97 (m, 1H), 1,391.37 (d, J = 6.62 Hz, 6H), 1.48-1.36 (m, 2H), 1.92 (m, 1H), 2.58-2, 52 (m, 1H), 2.78-2.64 (m, 3H), 2.93-2.90 (d, J = 7.35 Hz, 2H), 3.02-2.99 (m, 1H), 3.16-3.09 (m, 1H), 3.34-3.22 (m, 3H), 3.57 (s, 3H), 3.63-3.54 (m, 1H), 3.80-3.77 (d, J = 9.56 Hz, 1H), 4.0-3.93 (m, 2H) 4.55-4.40, (dd, J = 15.84, 29.42 Hz, 2H), 4.82 ( sa, 1H), 5.37-5.33 (d, J = 9.56 Hz, 1H), 6.70 (m, 1H), 6.88 (s at, 1H), 6.97 (s, 1H), 7.18-7.08 (m, 5H). Example 175 1H NMR (300 MHz, CD3OD) δ ppm 0.89 (s, 9 H), 0.99 (s, 9 H), 1.01 (s, 9 H), 1.24 (t, J = 8.30 Hz, 2 H), 2.42 (m, 1 H), 2.54 (s, 3 H), 2.75 (m, 6 H), 3.04 (m, 1 H), 3.16 (m, 1 H), 3.66 (s, 3 H), 3.74 (m, 1 H), 3.84 (s, 1 H), 4.13 (m, 2 H), 4.45 (dd, J = 15.8, 13.24 Hz, 2 H), 7.14 (m, 7 H), 7.72 (t, J = 7 , 72 Hz, 1 H). Example 176 1 H NMR (300 MHz, CDCl 3) δ ppm 0.88-0.78 (m, 15H), 1.07-0.95 (m, 1H), 1.39-1.37 (d, J = 6.99 Hz, 6H), 1.93-1.89 (m, 1H), 2.56-2.51 (m, 1H), 2.89-2.71 (m, 4H), 3.12-3.05 (m, 1H ), 3.34-3.20 (m, 3H), 3.62 (s, 3H), 3.63-3.54 (m, 2H), 3.79 (s, 3H), 3.92-3.82 (m, 3H), 4.10-4.02 (m, 1 H) 4.53-4.40 (dd , J = 15.45, 23.54 Hz, 2H), 4.72 (sa, 1H), 5.30-5.20 (m, 1H), 6.52-6.49 (m, 2H), 6.86-6.81 (m, 2H), 6.97 (s, 1H), 7, 23-7.05 (m, 7H). Example 177 1H NMR (300 MHz, CDCl3) δ ppm 0.84-0.76 (m, 15H), 1.03-0.91 (m, 1H), 1.39-1.37 (d, J = 6.99 Hz, 6H), 1.92-1.86 (m, 1H), 2.64-2.58 (m, 1H), 2.90-2.76 (m, 4H), 3.12-3.05 (m, 1H ), 3.34-3.20 (m, 3H), 3.59 (s, 3H), 3.64-3.59 (m, 2H), 4.12-3.86 (m, 4H), 4.53-4.40 (dd, J = 15.81, 25.74 Hz, 2H), 4.79 (sa, 1H ), 5.29-5.26 (d, J = 8.83 Hz, 1H), 6.56-6.53 (d, J = 9.56 Hz, 1H), 6.66 (sa, 1H), 6.97 (s, 1H), 7.25-7.05 (m, 6H) , 7.44-7.41 (d, J = 8.45 Hz, 2H), 7.787.69 (m, 2H), 7.96-7.93 (d, J = 8.45 Hz, 2H), 8.70-8.67 (m, 1 H). Example 178 1H NMR (300 MHz, DMSO d6) δ ppm 0.68 (s, 9H), 0.77-0.64 (m, 6H), 0.96-0.84 (m, 2H) 1.80 -1.70 (m, 1H), 2.44 (s, 3H), 2.81-2.60 (m, 5H), 3.03-2.93 (m, 3H), 3.50 (s, 3H), 3.69 -3.63 (m, 2H), 4.12-3.92 (m, 4H), 4.29 (s, 2H), 4.95-4.94 (d, J = 3.31 Hz, 1H), 6.98-6.95 (d, J = 9.56 Hz, 1H), 7.13-7.05 (m, 5H), 7.24-7.21 (m, 1H), 7.35-7.31 (m, 1H), 7.46-7.44 (d, J = 8.09 Hz, 3H), 7.56-7.52 (dd, J = 7.91, 2.39 Hz, 1H), 7.93-7.83 (m, 2H), 8.00-7.97 (d, J = 8.46 Hz, 2H), 8.36 (d, J = 2.21 Hz, 1H), 8.65 (d, J = 4.78 Hz, 1H), 9.13 (s, 1H). Example 179 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (d, J = 6.62 Hz, 3 H), 0.82 (s, 9 H), 0.87 (d, J = 7.35 Hz, 3 H), 1.00 (m, 2 H), 2.52 (d, J = 3.31 Hz, 1 H), 2.56 (d, J = 2.94 Hz, 1 H), 2.75 (m, 2 H), 2.87 (d, J = 8.09 Hz, 3 H), 2.94 (d, J = 12.87 Hz, 1 H), 3.12 (d, J = 4.78 Hz, 1 H), 3.30 (m, 2 H), 3.62 (s, 3 H), 3, 78 (s, 3 H), 3.86 (d, J = 7.35 Hz, 1 H), 3.91 (m, 1 H), 4.06 (m, 1 H), 4.55 (s, 2 H), 4.72 (s, 1 H), 5.28 (d, J = 8, 82 Hz, 1 H), 6.50 (d, J = 9.93 Hz, 2 H), 6.82 (d, J = 2.94 Hz, 1 H), 6.85 (s, 1 H), 7.09 (m, 1 H), 7.15 (m, 2 H), 7.18 (d, J = 6 , 25 Hz, 2 H), 7.22 (d, J = 2.21 Hz, 3 H), 7.34 (d, J = 5.15 Hz, 1 H), 7.37 (d, J = 4.78 Hz, 1 H), 8.21 (m, 2 H), 8.64 (dd, J = 4.78, 1.84 Hz, 2 H), 9.15 (d, J = 2.21 Hz, 1 H). Example 180 1 H NMR (300 MHz, CDCl 3) δ ppm 0.86 (m, 12 H), 1.03 (m, 9 H), 1.31 (m, 2 H), 1.44 (m, 1 H ), 1.91 (d, J = 6.99 Hz, 1 H), 2.53 (dd, J = 12.87, 4.04 Hz, 1 H), 2.71 (m, 2 H), 2.90 (d, J = 7 , 35 Hz, 2 H), 3.02 (d, J = 9.19 Hz, 1 H), 3.16 (m, 2 H), 3.31 (m, 2 H), 3.60 (s, 3 H), 3.76 (d, J = 9.56 Hz, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.02 (d, J = 7.72 Hz, 1 H), 4.56 (s, 3 H), 4.77 (s, 1 H), 5.35 (d, J = 9.19 Hz, 1 H), 6.65 (d, J = 8.09 Hz, 1 H), 6.73 (s, 1 H), 7.11 (m, 1 H), 7.17 (m, 5 H), 7.21 (s, 1 H), 7.35 (d, J = 4.78 Hz, 1 H), 7.38 (d, J = 4, 78 Hz, 1 H), 8.22 (m, 2 H), 8.65 (dd, J = 4.78, 1.84 Hz, 2 H), 9.15 (d, J = 1.47 Hz, 1 H). Example 181 1 H NMR (300 MHz, CDCl 3) δ ppm 0.84 (s, 12 H), 0.88 (m, 3 H), 1.02 (s, 9 H), 1.94 (d, J = 9.56 Hz, 1 H), 2.56 (m, 2 H), 2.66 (m, 2 H), 2.74 (m, 2 H), 2.91 (d, J = 7.35 Hz, 2 H), 3.17 (m, 1 H), 3.31 (m, 2 H), 3.59 (s, 3 H), 3.77 (d, J = 9.56 Hz, 1 H), 3.95 (d, J = 11.03 Hz, 1 H), 4.01 (d, J = 6.99 Hz, 1 H), 4, 56 (s, 3 H), 5.33 (s, 1 H), 6.66 (s, 1 H), 6.79 (s, 1 H), 7.11 (m, 2 H), 7.16 (m, 5 H), 7.21 (s, 1 H), 7.35 (d, J = 4, 78 Hz, 1 H), 7.38 (d, J = 4.78 Hz, 1 H), 8.22 (m, 2 H), 8.65 (dd, J = 4.96, 1.65 Hz, 1 H), 9.15 (d, J = 2.21 Hz, 1 H). Example 182 1 H NMR (300 MHz, CDCl 3), δ ppm 0.83 (s, 9 H), 0.93 (s, 9 H), 2.51 (m, 2 H), 2.63 (s, 3 H), 2.75 (m, 4 H), 3.07 (m, 2 H), 3.24 (m, 1 H), 3.59 (m, 2 H), 3.64 (s, 3 H), 3.79 (s, 3 H), 3.83 (d, J = 13.97 Hz, 1 H), 3.92 (d, J = 113.97 Hz, 1 H), 4.04 (m, 1 H), 4.61 (d, J = 15.08 Hz, 1 H), 4.69 (d, J = 15.08 Hz, 1 H), 5.29 (da, J = 8.82 Hz, 1 H), 6.21 (da, J = 9.56 Hz, 1 H), 6.38 (sa, 1 H), 6.54 (m, 1 H), 6.66 (m, 1 H), 6.85 (d, J = 8.82 Hz, 2 H), 7.00 (m, 5 H), 7.21 (d, J = 8.46 Hz, 2 H), 7.60 (d, J = 7.35 Hz, 1H), 7.67 (m, 1 H). Example 183 1 H NMR (300 MHz, CDCl 3), δ ppm 0.86 (s, 9 H), 0.98 (s, 9 H), 1.02 (s, 9 H), 1.39 (dd, J = 10.30, 5.88 Hz, 2 H), 2.53 (m, 2 H), 2.63 (s, 3 H), 2.76 (m, 4 H), 3.08 (dd, J = 9.38, 6, 43 Hz, 2 H), 3.25 (m, 1 H), 3.56 (da, J = 9.19 Hz, 1 H), 3.64 (s, 3 H), 3.73 (d, J = 9.56 Hz, 1 H), 4.03 (m, 1 H), 4.56 ( sa, 1 H), 4.66 (m, 2 H), 5.37 (da, J =

9.19 Hz, 1 H), 6.30 (d, J = 9.56 Hz, 1 H), 6.55 (m, 2 H), 6.66 (m, 1 H), 7.01 ( m, 5 H), 7.60 (m, 1 H), 7.67 (m, 1H). Example 184 1 H NMR (300 MHz, CDCl 3), δ ppm 0.82 (s, 9 H), 1.00 (s, 9 H), 2.40 (m, 1 H), 2.62 (dd, J = 12.32, 2.39 Hz, 1 H), 2.77-2.92 (m, 4 H), 3.07 (m, 2 H), 3.24 (m, 1 H), 3.62 (m, 1 H), 3.64 (s, 3 H), 3.78 (s, 3 H), 3.82 (d, J = 14.71 Hz, 1 H), 3.95 (d, J = 14.71 Hz, 1 H), 4.17 (s, 1 H), 4.25 (ca, J = 8.58 Hz, 1 H), 4.63 (d, J = 15.44 Hz, 1 H), 4.91 (m, 2 H), 5.30 (da, J = 8.82 Hz, 1 H), 6.42 (sa, 1 H), 6.83 (m, 3 H), 7.03 (s, 5 H), 7.18 (m, 3 H), 7.40 (m, 1 H), 7.51 (d, J = 8.09 Hz, 1 H), 7.83 (d, J = 8.09 Hz, 1 H), 10.86 (s a, 1 H). Example 185 1 H NMR (300 MHz, CDCl 3), δ ppm 0.83 (s, 9 H), 1.02 (s, 18 H), 1.37 (m, 2 H), 2.46 (m, 1 H), 2.61 (dd a, J = 12.69, 3.13 Hz, 1 H), 2.75 (m, 3 H), 2.90 (d, J = 8.09 Hz, 2 H), 3.10 (m, 2 H ), 3.24 (m, 1 H), 3.64 (m, 1 H), 3.65 (s, 3 H), 3.76 (d, J = 9.19 Hz, 1 H), 4.19 (s, 1 H), 4.24 (m, 1 H), 4.65 (d, J = 15 , 44 Hz, 1 H), 4.84 (sa, 1 H), 4.89 (d, J = 15.81 Hz, 1 H), 5.38 (da, J = 8.82 Hz, 1 H), 6.53 (sa, 1 H), 6.90 (m, 1 H), 7.05 ( s, 5 H), 7.16 (m, 1 H), 7.39 (m, 1 H), 7.49 (m, 1 H), 7.81 (d, J = 8.09 Hz, 1 H), 10.92 (s at, 1 H). Example 186 1 H NMR (300 MHz, CDCl 3), δ ppm 0.81 (m, 15 H), 1.00 (m, 1 H), 1.27 (m, 7 H), 1.41 (m, 1 H) , 1.57 (m, 2 H), 1.80-2.00 (m, 1H), 2.60 (dd, J = 12.32, 3.49 Hz, 1 H), 3.05 (m, 7 H), 3.62 (m, 4 H), 3.98 (m, 4 H), 4.48 (m, 2 H), 4.79 (sa, 1 H), 5.26 (d, J = 8.46 Hz, 1 H), 6.59 (m, 2 H), 7.18 (m, 8 H), 7.42 (d, J = 8.09 Hz, 2 H), 7.57 (t, J = 7.72 Hz, 1 H), 7.74 (m, 2 H), 7.94 (d, J = 8.46 Hz, 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 187 1 H NMR (300 MHz, CDCl 3), δ ppm 0.83 (s, 9 H), 0.95 (s, 9 H), 2.40 (m, 1 H), 2.54 (dd, J = 12.50, 2.21 Hz, 1 H), 2.69-2.80 (m, 4 H), 2.92-3.00 (m, 2 H), 3.23 (m, 1 H), 3.55 (m, 1 H), 3.59 (d, J = 9.19 Hz, 2 H), 3.64 (s, 3 H), 3.80 (s, 3 H), 3.83 (d, 1 H), 3.92 (d, 1 H), 4.05 (s, 3 H), 4.06-4.12 (m, 1 H), 4.66 (sa, 1 H), 4.75 (s, 2 H), 6.22 (da, J = 9.56 Hz, 1 H), 6.34 (s, 1 H), 6.85 (m, 2 H), 6.99 (m, 5 H), 7.14 (m, 1 H) , 7.22 (m, 2 H), 7.37 (m, 2 H), 7.88 (m, 1 H). Example 188 1 H NMR (300 MHz, CDCl 3) δ ppm 0.86 (s, 9 H), 0.99 (s, 9 H), 1.03 (s, 9 H), 1.39 (dd, J = 10.11, 6.07 Hz, 2 H), 2.47-2.57 (m, 2 H), 2.61-2.70 (m, 1 H), 2.72-2.83 (m, 4 H), 2.92- 3.01 (m, 2 H), 3.23 (m, 1 H), 3.58 (m, 1 H), 3.64 (s, 3 H), 3.73 (d, J = 9.56 Hz, 1 H), 4.05 (s, 3 H), 4.01-4.07 (m, 1H), 4.10 (s, 1 H), 4.58 (sa, 1 H), 4.72 (d, 1 H), 4.79 (d, 1 H), 5.37 (m, 1 H), 6.30 (da, 1 H), 6.51 (sa, 1 H), 7.01 (m, 5 H), 7.14 (m, 1 H), 7.37 (m, 2 H), 7.88 (m, 1 H). Example 189 1 H NMR (300 MHz, CDCl 3), δ ppm 0.88 (s, 9 H), 0.94 (s, 9 H), 1.04 (s, 9 H), 2.23 (m, 1 H), 2.50-2.58 (m, 1 H), 2.61 (s, 3 H), 2.62-2.69 (m, 1 H), 2.71-2.80 (m, 4 H), 2.89-3.04 ( m, 2 H), 3.20 (m, 1 H), 3.59 (m, 1 H), 3.67 (s, 3 H) 1 3.71 (d, J = 9.19 Hz, 1 H), 4.04 (s, 1 H), 4.13 (m, 1 H), 4.37 (d, J = 14, 71 Hz, 1 H), 4.59 (sa, 1 H), 4.70 (da, J = 14.71 Hz, 1 H), 5.37 (m, 1 H), 6.10 (da, 1 H), 6.44 (sa, 1 H), 6.90 (m, 5H), 7, 01 (m, 2 H), 7.15 (t, 1 H), 7.65 (d, J = 8.09 Hz, 1 H). Example 190 1 H NMR (300 MHz, CDCl 3), δ ppm 0.76 (d, J = 19.85 Hz, 9 H), 0.96 (m, 9 H) 1 1.35 (s, 9 H), 1.60 (s, 3 H), 2.61 (dd, J = 12.13, 2.94 Hz, 2 H), 2.84 (m, 4 H), 3.11 (s, 1 H), 3.30 (m, 2 H) , 4.03 (m, 5 H), 4.48 (m, 2 H), 4.73 (s, 1 H), 5.29 (d, J = 9.19 Hz, 1 H), 6.31 (d, J = 9.56 Hz, 1 H), 6.48 (s, 1 H), 7.14 (m, 8 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.57 (t, J = 7.72 Hz, 1 H), 7.74 (m, 2 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.69 (d, J = 4 , 78 Hz, 1 H). Example 191 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 15 H), 0.93 (m, 2 H), 1.04 (s, 2 H), 1.91 (s, 1 H ), 2.04 (s, 1 H), 2.63 (d, J = 4.07 Hz, 1 H), 2.78 (d, J = 11.19 Hz, 1 H), 2.89 (d, J = 7.46 Hz, 2 H), 3.08 (s, 1 H), 3.21 (m, 2 H), 3.35 (s, 1 H), 3.48 (m, 3 H), 3.60 (s, 3 H), 3.63 (s, 2 H), 3.88 (d, J = 11.19 Hz, 1 H), 3.98 (d, J = 9.49 Hz, 1 H), 4.04 (s, 1 H), 4.48 (s, 2 H), 4.70 (m, 2 H), 5.27 (m, 1 H), 6.58 (m, J = 7.12 Hz, 2 H), 7.17 (m, 5 H), 7.43 (d, J = 8.48 Hz, 2 H), 7.74 (m, 2 H), 7.95 (d, J = 8.48 Hz, 2 H), 8.68 (d, J = 4.75 Hz, 1 H). Example 193 1 H NMR (300 MHz, CDCl 3) δ ppm 0.84 (m, 4 H), 1.44 (d, J = 6.62 Hz, 3 H), 1.53 (m, 6 H), 1 , 90 (s, 1 H), 2.48 (s, 8 H), 3.11 (m, 4 H), 3.48 (s, 3 H), 3.52 (s, 3 H), 3.68 (m, 1 H), 3.92 (d, J = 11.40 Hz, 2 H), 4.12 (s, 2 H), 4.25 (s, 1 H), 4.47 (m, 1 H), 4.70 (s, 2H), 7.15 (m, 6H), 7.60 (m, 2H), 7.67 (s, 1 H), 7.91 (d, J = 7.72 Hz, 3 H), 8.24 (s, 1 H), 8.87 (s, 1 H). Example 194 1 H NMR (300 MHz, CDCl 3) δ ppm 0.85 (t, J = 7.17 Hz, 3 H), 1.04 (d, J = 4.41 Hz, 1 H), 1.39 ( d, J = 6.62 Hz, 3 H), 1.45 (t, J = 6.62 Hz, 6 H), 1.95 (s, 1 H), 2.46 (s, 7 H), 2.90 (s, 2 H), 2.90 (s, 1 H), 3.12 (m, 2 H), 3.22 (s, 2 H), 3.45 (m, 3 H), 3.71 (m, 2 H), 3.92 (s, 1 H), 4.06 (s, 2 H), 4.48 (s, 1 H), 4.68 (m, 2 H), 5.65 (s, 1 H), 6.91 (s, 1 H), 7.15 (m, 7 H), 7.41 (m, 2 H), 7.80 (d, J = 8.09 Hz, 1 H), 7.92 (m, 3 H), 8.81 (s, 1 H). Example 195 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (m, 6 H), 0.99 (s, 2 H), 1.25 (s, 1 H), 1.49 (s, 4 H ), 2.09 (s, 11 H), 2.65 (s, 1 H), 2.90 (d, J = 7.35 Hz, 2 H), 3.10 (s, 1 H), 3.22 (t, J = 9.01 Hz, 2 H), 3.48 (m, 3 H), 3.59 (s, 3 H), 3.62 (s, 2 H), 3.89 (m, 2 H), 4.09 (s, 1 H), 4.47 (d, J = 4.04 Hz, 2 H), 4.69 (d, J = 6, 25 Hz, 2 H), 5.17 (s, 1 H), 6.61 (s, 1 H), 7.14 (m, 6 H), 7.39 (d, J = 12.50 Hz, 1 H), 7.48 (d, J = 8.09 Hz, 2 H), 7.78 (d, J = 7 , 72 Hz, 1 H), 7.93 (m, 3 H), 8.83 (d, J = 5.15 Hz, 1 H). Example 196 1 H NMR (300 MHz, CDCl 3) δ ppm 0.75 (d, J = 6.62 Hz, 3 H), 0.81 (t, J = 7.35 Hz, 3 H), 1.00 ( m, 1 H), 1.38 (m, 1 H), 1.90 (d, J = 6.99 Hz, 1 H), 2.42 (dd, J = 12.50, 3.68 Hz, 1 H), 2, 71 (dd, J = 12.32, 9.74 Hz, 1 H), 2.90 (d, J = 7.72 Hz, 4 H), 3.01 (d, J = 9.56 Hz, 1 H), 3.12 (m, 1 H), 3.23 (m, 2 H) , 3.48 (m, 3 H), 3.57 (m, 3 H), 3.71 (d, J = 8.46 Hz, 2 H), 3.86 (d, J = 11.03 Hz, 1 H), 3.99 (s, 1 H), 4.17 (d, J = 7.72 Hz, 1 H), 4.46 (s, 3 H), 4.69 (m, 2 H), 5.12 (s, 1 H), 6.64 (s, 1 H), 6.75 (s, 1 H), 7.11 (m, 10 H), 7.22 (m, 2 H), 7.30 (m, 2 H), 7.73 (m, 2 H), 7.90 (d, J = 8.46 Hz, 2 H), 8.67 (d, J = 3.68 Hz, 1 H). Example 197 1 H NMR (300 MHz, CDCl 3) δ ppm 0.81 (m, 6 H), 1.08 (d, J = 10.30 Hz, 6 H), 1.32 (m, 5 H), 1 , 59 (s, 3 H), 1.91 (s, 1 H), 2.58 (s, 1 H), 2.82 (d, J = 9.56 Hz, 1 H), 2.92 (d, J = 7.72 Hz, 2 H), 3.01 (d, J = 8.82 Hz, 1H), 3.13 (s, 1 H), 3.22 (d, J = 8.09 Hz, 2 H), 3.47 (s, 3 H), 3.56 (s, 3 H), 3.60 (s, 2 H), 3.90 (m, 3 H), 4.02 (m, J = 13.97 Hz, 2 H), 4.46 (m, 2 H), 4.69 (s, 2 H), 4.89 (s, 1 H), 6.71 (s, 1 H), 6.96 (s, 1 H), 7.12 (s, 1 H), 7.14 (m, 6 H), 7.41 (d, J = 8.09 Hz, 2 H), 7.73 (m, 2 H), 7.96 (d, J = 7.72 Hz, 2 H), 8.68 (d, J = 4.41 Hz, 1 H). Example 198 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (m, 12 H), 1.56 (s, 1 H), 2.12 (m, 1 H), 2.61 (m, 1 H ), 2.68 (s, 3 H), 2.80 (dd, J = 12.50, 9.93 Hz, 1 H), 2.88 (t, J = 7.17 Hz, 2 H), 3.13 (m, 1 H) , 3.23 (m, 2 H), 3.59 (s, 3 H), 3.65 (m, 2 H), 3.78 (d, J = 11.03 Hz, 1 H), 3.93 (d, J = 13.97 Hz, 1 H), 3.98 (d, J = 11.40 Hz, 2 H), 4.07 (m, 2 H), 4.45 (d, J =

4.78 Hz, 2 H), 4.76 (s, 1 H), 5.25 (d, J = 8.82 Hz, 1 H), 6.55 (m, J = 9.93 Hz, 2 H), 6.96 (s, 1 H), 7.17 (m, 5 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.74 (m, 3 H), 7.94 (d, J = 8.46 Hz, 2 H), 8.68 (d, J = 4 , 78 Hz, 1 H). Example 200 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (m, 15 H), 1.00 (m, 1 H), 1.31 (s, 1 H), 1.90 (s, 1 H ), 2.61 (dd, J = 12.32, 2.76 Hz, 1 H), 2.84 (m, 5 H), 3.03 (m, 3 H), 3.61 (m, 3 H), 3.92 (m, 1 H), 3.99 (d, J = 12.50 Hz, 2 H), 4.09 (m, 1 H), 4.81 (m, 3 H), 5.26 (d, J = 9.93 Hz, 1 H), 6.51 (d, J = 9.56 Hz, 2 H), 7, 08 (m, 5 H), 7.24 (m, 2 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.60 (dd, J = 7.72, 6.25 Hz, 1 H), 7.74 (m, 3 H), 7.95 (d, J = 8, 09 Hz, 2 H), 8.14 (d, J = 7.72 Hz, 1 H), 8.20 (d, J = 7.72 Hz, 1 H), 8.68 (d, J = 4.04 Hz, 1 H), 8.88 (d, J = 4.41 Hz, 1 H) . Example 201 1 H NMR (300 MHz, CDCl 3) δ ppm 0.81 (m, 6 H), 1.27 (s, 3 H), 1.92 (s, 2 H), 2.08 (s, 1 H ), 2.58 (d, J = 10.66 Hz, 1 H), 2.89 (m, 3 H), 3.01 (s, 1 H), 3.06 (d, J = 10.66 Hz, 2 H), 3.68 ( d, J = 10.66 Hz, 2 H), 3.76 (s, 2 H), 3.84 (m, 1 H), 3.91 (d, J = 11.03 Hz, 1 H), 3.99 (d, J = 9.19 Hz, 1 H), 4.13 (d, J = 8.82 Hz, 1 H), 4.26 (s, 1 H), 4.76 (d, J = 15.44 Hz, 1 H), 4.87 (m, 1 H), 5.21 (s, 1 H), 5.53 (s, 1 H), 6.42 (d, J = 9 , 93 Hz, 1 H), 7.10 (m, 5 H), 7.23 (m, 1 H), 7.28 (s, 1 H), 7.41 (d, J = 8.09 Hz, 2 H), 7.59 (m, 1 H), 7.74 (m, 3 H), 7.97 (d, J = 8.09 Hz, 2 H), 8.13 (d, J = 7.72 Hz, 1 H), 8.20 (d, J = 8.46 Hz, 1 H), 8.69 (d, J = 4.41 Hz, 1 H), 8.87 (d, J = 4.04 Hz , 1 HOUR). Example 202 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (dd, J = 11.95, 7.17 Hz, 6 H), 0.89 (s, 9 H), 1.35 (s, 1 H), 1.96 (s, 1 H), 2.69 (s, 1 H), 2.89 (d, J = 8.46 Hz, 5 H), 3.06 (dd, J = 6.62, 2.94 Hz, 5 H ), 3.23 (s, 1 H), 3.42 (s, 1 H), 3.57 (s, 2 H), 3.75 (s, 1 H), 3.95 (m, 2 H), 4.14 (m, 1 H), 4.43 (s, 1 H), 4.81 (d, J = 10.30 Hz, 1 H), 4.88 (s, 1 H), 6.56 (d, J = 9.93 Hz, 1 H), 6.99 (s, 1 H), 7.10 (m, 5 H), 7.22 (m, 2 H), 7.44 (d, J = 8.09 Hz, 2 H), 7.60 (m, 1 H), 7.72 (m, 3 H), 7.93 (d, J = 8.09 Hz, 2 H), 8.14 (d, J = 8.46 Hz, 1 H), 8.19 (m, 1 H), 8.68 (d, J = 4 , 04 Hz, 1 H), 8.88 (t, J = 3.68 Hz, 1 H). Example 203 1 H NMR (300 MHz, CDCl 3) δ ppm 0.86 (m, 6 H), 0.98 (m, 2 H), 1.26 (s, 2 H), 1.38 (m, 2 H ), 1.99 (m, 6 H), 2.00 (m, 3 H), 2.67 (dd, J = 12.13, 2.21 Hz, 1 H), 2.91 (m, 2 H), 3.08 (m, 1 H), 3.69 (d, J = 9.19 Hz, 1 H), 3.96 (d, J = 11.03 Hz, 1H), 4.05 (d, J = 13.97 Hz, 1 H), 4.12 (d, J = 10.66 Hz, 1 H), 4.18 (m, 2 H), 4.75 (m, 1 H), 4.89 (m, 1 H), 6.52 (d, J = 9.56 Hz, 1 H), 6.93 (m, 2 H), 7.10 (m, 3 H), 7.16 (m, 2 H), 7.23 (m, 1 H), 7.28 (d, J = 4.41 Hz, 1 H), 7.45 (s, 1 H), 7.48 (d, J = 8.09 Hz, 2 H), 7.59 (m, 1 H), 7.74 (m, 3 H), 7.97 (m, 2 H), 8.13 (d, J = 7.72 Hz, 1 H), 8.20 (d, J = 7.72 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H), 8.87 (d, J = 4.41 Hz, 1 H). Example 204 1 H NMR (300 MHz, CDCl 3) δ ppm 0.84 (m, 6 H), 1.01 (m, 2 H), 1.35 (m, 2 H), 1.92 (s, 1 H ), 2.14 (s, 3 H), 2.58 (dd, J = 12.50, 2.21 Hz, 1 H), 2.86 (m, 2 H), 3.03 (m, 2 H), 3.60 (s, 1 H) , 3.93 (d, J = 11.03 Hz, 1 H), 4.02 (d, J = 14.34 Hz, 1 H), 4.09 (s, 1 H), 4.44 (m, 2 H), 4.65 (s, 1 H), 4.76 (d, J = 15.44 Hz, 1 H), 4.87 (m, 1 H), 6.45 (d, J = 9.93 Hz, 1 H), 6.57 (d, J = 8.09 Hz, 1 H), 6.90 (t, J = 6.99 Hz, 1 H), 7.05 (m, 4 H), 7.12 (m, 5 H), 7.23 (dd, J = 6.80, 2.02 Hz, 1 H), 7.28 (s, 1 H), 7.33 (d, J = 8.09 Hz, 2 H), 7.61 (m, 1 H), 7.75 (m, 3 H), 7.95 (m, 2 H), 8.13 (d, J = 8.46 Hz, 1 H), 8.20 (d, J = 7.72 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H), 8.87 (d, J = 4.41 Hz, 1 HOUR). Example 205 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (d, J = 6.62 Hz, 3 H), 0.87 (m, 3 H), 1.05 (s, 1 H), 1 , 24 (m, 1 H), 1.40 (s, 1 H), 1.95 (s, 3 H), 2.58 (d, J = 12.87 Hz, 1 H), 2.84 (s, 1 H), 2.93 (m, 2 H), 3.09 (m, 3 H), 3.74 (d, J = 10.66 Hz, 1 H), 3.99 (m, 2 H), 4.14 (m, 1 H), 4.75 (d, J = 15.44 Hz, 1 H), 4.91 (d, J = 15.08 Hz, 1 H), 5.76 (s, 1 H), 6.32 (d, J = 6.99 Hz, 1 H), 6.44 (s, 1 H), 6.61 (d, J = 9.19 Hz, 1 H), 6.78 (d, J = 7.72 Hz, 1 H), 6.90 (t, J = 7.72 Hz, 1 H), 7.13 (m, 3 H), 7.20 (m, 3 H), 7.23 (d, J = 1.84 Hz, 1 H), 7.28 (d, J = 4.41 Hz, 1 H) , 7.49 (d, J = 8.09 Hz, 2 H), 7.59 (m, 1 H), 7.73 (m, 3 H), 7.97 (d, J = 8.09 Hz, 2 H), 8.12 (d, J = 8.46 Hz, 1 H), 8.19 (d, J = 8.46 Hz, 1 H), 8.67 (d, J = 4.78 Hz, 1 H), 8.86 (d, J = 4.41 Hz, 1 H). Example 206 1 H NMR (300 MHz, CDCl 3) δ ppm 0.55 (t, J = 6.43 Hz, 3 H), 0.82 (m, 9 H), 0.88 (m, 2 H), 0 , 97 (m, 1 H), 1.38 (m, 2 H), 1.54 (s, 2 H), 1.94 (s, 1 H), 2.71 (s, 1 H), 2.84 (m, 3 H), 2.97 (m, 1 H), 3.07 (m, 2 H), 3.12 (m, 1 H), 3.24 (m, 2 H), 3.33 (s, 1 H), 3.51 (d, J = 11.40 Hz, 1 H), 3.64 (m, 1 H), 3.95 (m, 2 H), 4.15 (m, 1 H), 4.42 (s, 1 H), 4.82 (m, 3 H), 6.55 (d, J = 9.56 Hz, 1 H), 7.09 (m, 5 H), 7.22 (m, 2 H), 7.46 (d, J = 8.09 Hz, 2 H), 7.61 (m, 1 H), 7.74 (m, 3 H), 7.93 (d, J = 8.46 Hz, 2 H), 8.14 (d, J = 8.46 Hz, 1 H), 8.20 (d, J = 8.82 Hz, 1 H), 8.67 (d, J = 4.78 Hz, 1 H), 8.88 (d, J = 4.04 Hz, 1 H). Example 207 1 H NMR (300 MHz, CDCl 3) δ ppm 0.58 (d, J = 6.25 Hz, 3 H), 0.83 (d, J = 13.97 Hz, 9 H), 1.03 ( s, 1 H), 1.26 (s, 4 H), 1.95 (s, 1 H), 2.98 (d, J = 50.37 Hz, 10 H), 3.70 (s, 2 H), 3.95 (s, 2 H), 4.11 (s, 2 H), 4.51 (s, 1 H), 4.80 (d, J = 42.65 Hz, 2 H), 5.32 (m, 1 H), 6.59 (d, J = 9.56 Hz, 1 H), 7.11 (d, J = 2 , 21 Hz, 6 H), 7.39 (d, J = 7.72 Hz, 1 H), 7.74 (d, J = 38.24 Hz, 7 H), 7.95 (s, 1 H), 8.17 (m, 2 H), 8.69 (s, 1 H), 8.87 (s, 1 H). Example 208 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (m, 6 H), 0.90 (d, J = 4.78 Hz, 2 H), 1.38 (m, 1 H), 1 , 90 (s, 1 H), 2.61 (d, J = 2.57 Hz, 2 H), 2.87 (m, 1 H), 3.02 (m, 2 H), 3.68 (s, 1 H), 3.89 (d, J = 11.03 Hz, 1 H), 4.00 (s, 2 H), 4.12 (c, J = 6.99 Hz, 2 H), 4.53 (d, J = 13.24 Hz, 1 H), 4.77 (d, J = 15.08 Hz, 1H), 4.85 (m, 1 H), 5.08 (s, 2 H), 5.62 (s, 1 H), 6.40 (d, J = 1.10 Hz, 1 H), 7.09 (m, 7 H), 7.23 (m, 2 H), 7.28 (d, J = 4, 41 Hz, 3 H), 7.39 (d, J = 8.09 Hz, 2 H), 7.60 (m, 1 H), 7.75 (m, 3 H), 7.95 (d, J = 8.09 Hz, 2 H), 8.14 (m, 1 H), 8.20 (d, J = 7.72 Hz, 1 H), 8.69 (d, J = 4.78 Hz, 1 H), 8.88 (d, J = 4.04 Hz, 1 H). Example 209 1 H NMR (300 MHz, CDCl 3) δ ppm 0.76 (t, J = 6.43 Hz, 3 H), 0.85 (m, 12 H), 0.99 (m, 1 H), 1 , 22 (t, J = 6.99 Hz, 2 H), 1.29 (m, 2 H), 1.89 (s, 1 H), 2.63 (d, J = 3.31 Hz, 1 H), 2.84 ( m, 4 H), 3.02 (m, 3 H), 3.02 (m, 2 H), 3.61 (d, J = 9.56 Hz, 2 H), 3.95 (m, 2 H), 4.09 (m, 2 H), 4.81 (m, 2 H), 5.22 (d, J = 8.09 Hz, 1 H), 6.50 (d, J = 9.56 Hz, 2 H), 7.08 (m, 5 H), 7.22 (m, 2 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.60 (t, J = 6.99 Hz, 1 H), 7.73 (m, 3 H), 7.95 (d, J = 8.46 Hz, 2 H), 8.14 (d, J = 7.72 Hz, 1 H), 8.20 (d, J = 8.09 Hz, 1 H), 8.68 (d, J = 4.41 Hz , 1 H), 8.88 (d, J = 4.41 Hz, 1 H). Example 210 1 H NMR (300 MHz, CDCl 3) δ ppm 0.81 (m, 15 H), 0.98 (m, 1 H), 1.33 (m, 1 H), 1.93 (s, 3 H ), 2.64 (dd, J = 12.50, 2.94 Hz, 1 H), 2.84 (m, 5 H), 3.04 (m, 3 H), 3.58 (s, 1 H), 3.96 (m, 4 H), 4.09 (m, 1 H), 4.81 (m, 2 H), 6.04 (d, J = 9.19 Hz, 1 H), 6.55 (d, J = 9.19 Hz, 1 H), 6.83 (s, 1 H), 7.09 (m, 5 H), 7, 22 (m, 1 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.60 (m, 1 H), 7.73 (m, 4 H), 7.94 (d, J = 8.46 Hz, 2 H), 8.14 (d, J = 7.35 Hz, 1 H), 8.19 (d, J = 7.72 Hz, 1 H), 8.68 (d, J = 4.78 Hz, 1 H), 8.87 (d, J = 4.41 Hz, 1 H). Example 212 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.65 (d, J = 6.62 Hz, 3 H), 0.70 (d, J = 6.62 Hz, 3 H), 0, 76 (t, J = 7.35 Hz, 3 H), 0.82 (t, J = 7.35 Hz, 3 H), 0.96 (m, 2 H), 1.32 (m, 2 H), 1.59 ( m, 1 H), 1.84 (m, J = 14.71, 14.71 Hz, 1

H), 2.76 (m, 8 H), 3.08 (m, 4 H), 3.62 (s, 3 H), 3.73 (d, J = 7.72 Hz, 1 H), 3.83 (d, J = 8.09 Hz, 1 H), 3.95 (s, 2 H), 4.20 (m, 1 H), 4.88 (s, 2 H), 5.97 (s, 2 H), 6.86 (m, 1 H), 6.95 (d, J = 7.35 Hz, 1 H), 7.06 (m, 4 H), 7.43 (m, 5 H), 7.47 (d, J = 4.41 Hz, 2 H), 7.67 (t, J = 7.72 Hz, 1 H), 7.80 (m, 1 H), 8.08 (d, J = 7.72 Hz, 1 H), 8.32 (d, J = 7.72 Hz, 1 H), 8.83 (d, J = 4.41 Hz, 1 H). Example 213 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.60 (m, 3 H), 0.77 (m, 6 H), 0.87 (m, 3 H), 1.03 (m, 2 H), 1.33 (m, 2 H), 1.54 (d, J = 17.65 Hz, 1 H), 1.89 (s, 1 H), 2.23 (s, 3 H), 2.39 (s, 3 H) , 2.81 (m, 8 H), 3.19 (m, 2 H), 3.63 (m, 3 H), 3.70 (d, J = 8.09 Hz, 1 H), 3.85 (s, 1 H), 3.95 (m, 3 H), 4.25 (s, 1 H), 5.05 (m, 2 H), 7.05 (m, 3 H), 7.15 (m, 2 H), 7.26 (d, J = 8.09 Hz, 2 H), 7.52 (d, J = 8.09 Hz, 2 H), 7.78 (d, J = 5.15 Hz, 1H), 7.89 (m, 2 H), 8.05 (m, 1 H), 8.19 (d, J = 8.46 Hz, 1 H), 8.52 (d, J = 8.46 Hz, 1 H), 9.05 (d, J = 5.15 Hz, 1 H). Example 214 1H NMR (300 MHz, MeOH-d4) δ ppm 0.63 (d, J = 6.99 Hz, 3 H), 0.73 (m, 6 H), 0.82 (m, 3 H) , 0.98 (s, 2H), 1.29 (s, 2 H), 1.56 (s, 1 H), 1.85 (s, 1 H), 2.62 (s, 1 H), 2.76 (m, 3 H), 2.84 (m, 2 H), 3.07 (m, 2 H), 3.31 (m, 2 H), 3.60 (s, 3 H), 3.71 (d, J = 8.09 Hz, 1 H), 3.84 (s, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.00 (s, 2 H), 4.23 (s, 1 H), 4.89 (s, 3 H), 6.97 (m, 2 H), 7.09 (d, J = 6.62 Hz, 2 H), 7.48 (d, J = 4.41 Hz, 1 H), 7, 57 (d, J = 8.46 Hz, 2 H), 7.68 (m, 5 H), 7.81 (m, 2 H), 8.08 (d, J = 8.46 Hz, 1 H), 8.32 (d, J = 7.72 Hz, 1H), 8.57 (d, J = 6.25 Hz, 2 H), 8.84 (d, J = 4.41 Hz, 1 H). Example 215 1 H NMR (300 MHz, CDCl 3) δ ppm 0.85 (m, 3 H), 0.91 (m, J = 5.52 Hz, 12 H), 1.02 (m, 1 H), 1 , 42 (m, 1 H), 1.98 (m, 1 H), 2.54 (s, 3 H), 2.78 (m, 2 H), 2.92 (d, J = 7.72 Hz, 2 H), 3.06 (c, J = 8.33 Hz, 1 H), 3.21 (m, 3 H), 3.63 (s, 3 H), 3.67 (s, 2 H), 3.78 (d, J = 8.82 Hz, 1 H), 4.00 (d, J = 11.40 Hz, 1 H), 4.11 (m, 1 H), 4.49 (m, 2 H), 4.80 (s, 2 H), 5.41 (d, J = 9.56 Hz, 1 H), 7.04 (m, 2 H), 7.15 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 217 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (d, J = 6.44 Hz, 3 H), 0.82 (s, 9 H), 0.86 (t, J = 7.12 Hz, 3 H), 1.01 (s, 1 H), 1.03 (m, 4 H), 1.43 (s, 1 H), 1.93 (s, 1 H), 2.31 (s, 3 H), 2.53 (d, J = 12.54 Hz, 1 H), 2.74 (s, 1 H), 2.87 (d, J = 7.46 Hz, 2 H), 2.94 (s, 1 H), 3.14 (s, 1 H), 3.24 (s, 1 H), 3.62 (m, 4 H), 3.62 (s, 3 H), 3.86 (m, 2 H), 4.11 (m, 2 H), 4.71 (s, 1 H), 5.26 (d, J = 9.15 Hz, 1 H), 6.44 (s, 1 H), 7.12 (m, 12 H). Example 218 1 H NMR (300 MHz, CDCl 3) δ ppm 0.85 (m, 3 H), 0.89 (m, 3 H), 0.95 (s, 1 H), 1.00 (s, 9 H ), 1.06 (m, 2 H), 1.13 (s, 3 H), 1.26 (s, 1 H), 1.70 (s, 4 H), 1.89 (s, 1 H), 1.93 (s, 1 H), 2.49 (dd, J = 6.99, 3.68 Hz, 2 H), 2.54 (s, 3H), 2.63 (m, 1 H), 2.90 (d, J = 7.72 Hz, 3 H), 3.15 (m, 4 H), 3.55 (d, J = 9, 19 Hz, 1 H), 3.63 (s, 3H), 3.70 (d, J = 9.19 Hz, 1H), 3.93 (d, J = 11.03 Hz, 1 H), 4.06 (s, 1H), 4.47 (m, 2 H), 4.65 (s, 1 H) , 5.35 (m, 1H), 6.41 (s, 1 H), 6.50 (d, J = 9.19 Hz, 1 H), 7.05 (dd, J = 11.58, 7.54 Hz, 2 H), 7.12 (m, 1 H), 7.17 (m, 4 H), 7.53 (t, J = 7.72 Hz, 1 H). Example 219 1 H NMR (300 MHz, CDCl 3) δ ppm 0.87 (m, 9 H), 0.93 (d, J = 6.62 Hz, 3 H), 0.99 (s, 9 H), 1 , 07 (m, 1 H), 1.42 (m, 1 H), 1.68 (d, J = 7.35 Hz, 1 H), 1.97 (s, 1 H), 2.45 (m, 2 H), 2.56 (m, 4 H), 2.63 (m, 1 H), 2.90 (d, J = 7.35 Hz, 2 H), 3.15 (m, 3 H), 3.56 (d, J = 8.82 Hz, 1H), 3.63 (s, 3 H), 3.70 (d, J = 9.93 Hz, 1 H), 3.93 (d, J = 11.03 Hz, 1 H), 4.09 (d, J = 8.82 Hz, 1 H), 4.47 (m, 2 H), 4.66 (s, 1 H), 5.32 (d, J = 13.97 Hz, 1H), 6.44 (s, 1 H), 6.51 (d, J = 9.56 Hz, 1 H), 7.05 (dd, J = 11.77, 7.72 Hz, 2 H), 7.14 (m, 5 H), 7.53 (t, J = 7.72 Hz, 1 H ). Example 220 1 H NMR (300 MHz, CDCl 3) δ ppm 0.86 (m, 3 H), 0.92 (d, J = 10.30 Hz, 3 H), 1.01 (d, J = 5.88 Hz, 9 H), 1.07 (m, 1 H), 1.50 (s, 1H), 1.92 (s, 1 H), 2.49 (s, 3 H), 2.72 (m, 5 H), 2 , 96 (t, J = 7.91 Hz, 4 H), 3.23 (m, 4 H), 3.55 (s, 3 H), 3.66 (m, 1 H), 3.80 (d, J = 8.46 Hz, 1 H), 3.93 (s, 1 H), 3.98 (d, J = 11 , 40 Hz, 1 H), 4.47 (m, 2 H), 5.30 (m, 1 H), 6.85 (s, 1 H), 6.99 (d, J = 7.72 Hz, 1 H), 7.07 (m, 3 H), 7.17 (m, 8 H), 7.52 (m, 1 H). Example 221 1H NMR (300 MHz, CDCl3) δ ppm 0.87 (m, 6 H), 0.92 (s, 9 H), 1.44 (m, 1 H), 1.94 (s, 1H) , 2.54 (s, 3 H), 2.60 (dd, J = 12.32, 3.49 Hz, 1 H), 2.73 (m, 1 H), 2.90 (d, J = 7.72 Hz, 2 H), 2, 96 (d, J = 8.82 Hz, 1 H), 3.16 (m, 3 H), 3.55 (d, J = 8.09 Hz, 1 H), 3.62 (s, 3 H), 3.66 (d, J = 9.19 Hz, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.07 (m, 1 H), 4.16 (m, 2 H), 4.46 (s, 2 H), 4.65 (s, 1 H), 5.28 (d, J = 8.46 Hz, 1 H), 6.57 (d, J = 8 , 82 Hz, 1 H), 6.72 (s, 1 H), 6.90 (m, 1 H), 6.96 (m, 1 H), 7.05 (dd, J = 11.95, 7.54 Hz, 2 H), 7.14 (m, 5 H), 7.23 (d, J = 1 , 47 Hz, 1 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 222 1 H NMR (300 MHz, CDCl 3) δ ppm 0.65 (d, J = 6.62 Hz, 3 H), 0.73 (s, 9 H), 0.81 (t, J = 7.35 Hz, 3 H), 0.98 (m, 1 H), 1.38 (m, 1 H), 1.87 (s, 1 H), 2.54 (s, 3 H), 2.61 (m, 1 H), 2.82 (m, 1 H), 2.90 (m, 6 H), 3.08 (m, 1 H), 3.18 (m, 3 H), 3.56 (s, 2 H), 3.60 (d, J = 9.93 Hz, 1 H), 3.85 (d, J = 11.03 Hz, 1 H), 4.06 (d, J = 5.52 Hz, 2 H), 4.47 (s, 1H), 5.24 (d, J = 6.99 Hz, 1 H), 6.55 (d, J = 8.09 Hz, 1 H), 6.62 (s, 1 H), 7.06 (dd, J = 10.30, 7.72 Hz, 1 H), 7.13 (m, 1 H), 7.15 (m, 5 H), 7.46 (m, 2 H), 7.51 (m, 2 H), 7.68 (s, 1 H), 7.75 (s, 1 H), 7.79 (m, 2 H). Example 223 1 H NMR (300 MHz, CDCl 3) δ ppm 0.77 (s, 9 H), 0.81 (d, J = 6.62 Hz, 3 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.22 (m, 6 H), 1.39 (m, 2 H), 1.94 (s, 1 H), 2.56 (m, 3 H), 2.78 (dd, J = 12, 50, 10.30 Hz, 1 H), 2.88 (m, 4 H), 3.16 (m, 3 H), 3.58 (s, 2 H), 3.62 (m, 3 H), 3.81 (d, J = 113.60 Hz, 1 H), 3.93 (m, 2 H) , 4.07 (m, 1H), 4.48 (s, 2 H), 4.75 (s, 1 H), 5.25 (m, 1 H), 6.42 (s, 1 H), 6.52 (d, J = 9.56 Hz, 1 H), 7.14 (m, 11 H), 7.55 (s, 1 H). Example 224 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 12 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.07 (m, 1 H), 1 , 32 (dd, J = 5.88.1.84 Hz, 6H), 1.43 (m, 1 H), 1.92 (s, 1 H), 2.54 (s, 3 H), 2.56 (d, J = 3.31 Hz, 1H), 2.76 (dd, J = 12.13, 10.30 Hz, 1 H), 2.89 (d, J = 7.72 Hz, 5 H), 3.15 (m, 2 H), 3.60 (s, 2 H), 3.62 (s, 3 H) , 3.84 (m, 2 H), 3.91 (d, J = 11.03 Hz, 1 H), 4.07 (t, J = 6.62 Hz, 1 H), 4.48 (m, 3 H), 4.73 (s, 1 H), 5.28 (d, J = 13.24 Hz, 1 H), 6.46 (s, 1 H), 6.53 (d, J = 9.19 Hz, 1 H), 6.81 (d, J = 8.82 Hz, 2 H), 7.06 (m, 2 H), 7.19 (m, 5 H), 7.54 (t, J = 7 , 72 Hz, 1 H). Example 225 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (d, J = 6.62 Hz, 3 H), 0.82 (s, 9 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.06 (m, 1 H), 1.44 (m, 1 H), 1.95 (s, 1 H), 2.22 (s, 6 H), 2.50 (d, J = 2, 94 Hz, 1 H), 2.54 (s, 3 H), 2.75 (m, 1H), 2.90 (t, J = 8.09 Hz, 3 H), 3.16 (m, 2 H), 3.54 (d, J = 10.30 Hz, 1 H), 3.61 (d, J = 4.78 Hz , 3 H), 3.85 (d, J = 5.52 Hz, 2 H), 3.91 (m, 1 H), 4.05 (d, J = 7.72 Hz, 1 H), 4.47 (s, 2 H), 4.72 (s, 1 H), 5.30 (s, 1 H), 6.52 (m, J = 9.19 Hz, 2 H), 7.05 (m, 7 H), 7.18 (m, 4 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 226 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 12 H), 0.87 (t, J = 7.17 Hz, 3 H), 1.04 (m, 1 H), 1 , 26 (s, 1 H), 1.41 (m, 1 H), 1.95 (s, 1 H), 2.54 (s, 3 H), 2.58 (dd, J = 12.87, 2.94 Hz, 1 H) , 2.78 (m, 1 H), 2.90 (d, J = 7.72 Hz, 3 H), 3.16 (m, 2 H), 3.59 (s, 1 H), 3.61 (s, 3 H), 3.79 (s, 3 H), 3.83 (d, J = 13, 97 Hz, 1 H), 3.91 (d, J = 7.72 Hz, 1 H), 3.95 (m, 1 H), 4.09 (m, 1 H), 4.47 (m, 2 H), 4.78 (d, J = 1.47 Hz, 1 H), 5.28 (m, 1 H), 6.50 (s, 1 H), 6.55 (d, J = 9.56 Hz,

1H), 6.79 (dd, J = 8.09, 2.57 Hz, 1 H), 6.84 (d, J = 7.72 Hz, 1 H), 6.92 (d, J = 5 , 52 Hz, 1H), 7.05 (dd, J = 12.50, 7.72 Hz, 2 H), 7.15 (m, 6 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 227 1 H NMR (300 MHz, CDCl 3) δ ppm 0.83 (dd, J = 13.42, 6.80 Hz, 9 H), 0.88 (m, 3 H), 1.00 (s, 9 H), 1.05 (m, 1 H), 1.31 (m, 5 H), 1.42 (s, 1 H), 1.53 (s, 1 H), 1.93 (s, 1 H), 2.51 (s, 2 H), 2.54 (s, 3 H), 2.62 (m, 1 H), 2.90 (d, J = 7.72 Hz, 2 H), 3.17 (m, 3 H), 3.55 (d, J = 8.09 Hz, 1 H), 3.64 (s, 3 H), 3.71 (d, J = 9.56 Hz, 1 H), 3.92 (d, J = 11.40 Hz, 1 H), 4.07 (s, 1 H), 4.47 (m, 2 H), 4.63 (s, 1 H), 5.32 (d, J = 9.56 Hz, 1 H), 6.40 (s, 1 H), 6.50 (d, J = 9.19 Hz, 1 H), 7.05 (dd, J = 12.32, 7.54 Hz, 2 H), 7.14 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H) . Example 228 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 12 H), 0.87 (t, J = 7.35 Hz, 3 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.02 (m, 1 H), 1.21 (t, J = 7.72 Hz, 3 H), 1.42 (m, 1 H), 1.91 (m, J = 6.25 Hz, 1 H), 2.54 (s, 3 H), 2.90 (m, 3 H), 3.14 (m, 3 H), 3.56 (d, J = 12.87 Hz, 2 H), 3.61 (s, 3 H), 3.83 (m, 1 H), 3.90 (d, J = 5.15 Hz, 1 H), 3.94 (m, 1 H), 4.07 (m, J = 8.09 Hz, 1 H), 4.47 (m, 2 H), 4.73 (s, 1 H), 5.26 (d, J = 8.46 Hz, 1 H), 6.46 (s, 1H), 6.52 (d, J = 9.56 Hz, 1 H), 7.06 (m, 2 H), 7.15 (m, 9 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 229 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (m, 12 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.03 (m, 1 H), 1 , 42 (m, 1 H), 1.95 (s, 1 H), 2.31 (s, 3 H), 2.54 (s, 3 H), 2.57 (d, J = 3.31 Hz, 1 H), 2.77 (m, 1 H), 2.89 (d, J = 7.72 Hz, 3 H), 3.16 (m, 2 H), 3.61 (d, J = 9.19 Hz, 2 H), 3.60 (d, J = 4.41 Hz, 3 H), 3.88 (m, 3 H), 4, 05 (m, 1 H), 4.47 (s, 2 H), 4.75 (s, 1 H), 5.27 (d, J = 9.19 Hz, 1 H), 6.50 (s, 1 H), 6.54 (d, J = 9.19 Hz, 1 H), 7.08 (m, 6 H), 7.18 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 230 1 H NMR (300 MHz, CDCl 3) δ ppm 0.75 (m, 12 H), 0.86 (t, J = 7.35 Hz, 3 H), 1.05 (m, 1 H), 1 , 40 (m, 2 H), 1.93 (d, J = 6.25 Hz, 1 H), 2.54 (s, 3H), 2.62 (dd, J = 72.69, 3.86 Hz, 1 H), 2.79 (m, 1 H), 2.92 (m, 2 H), 3.16 (m, 2 H), 3.59 (s, 3 H), 3.92 (t, J = 10.66 Hz, 3 H), 4.06 (m, 1H), 4.48 (s, 2H), 4.80 (s , 1 H), 5.22 (d, J = 9.19 Hz, 1 H), 6.63 (d, J = 8.82 Hz, 1 H), 6.71 (s, 1 H), 7.06 (t, J = 8.27 Hz, 2 H), 7.06 (t, J = 8.27 Hz, 2 H), 7.16 (m, 5 H), 7.49 (t, J = 9.01 Hz, 2 H), 7.55 (m, 3 H). Example 231 1 H NMR (300 MHz, CDCl 3) δ ppm 0.77 (d, J = 6.25 Hz, 3 H), 0.87 (m, 12 H), 1.02 (m, 2 H), 1 , 39 (d, J = 24.27 Hz, 1 H), 1.91 (s, 1 H), 2.47 (s, 1 H), 2.56 (s, 3 H), 2.74 (dd, J = 12.50 , 9.93 Hz, 1 H), 2.90 (d, J = 7.72 Hz, 2 H), 2.97 (s, 1 H), 3.18 (m, 3 H), 3.59 (s, 3 H), 3.66 (d, J = 9.19 Hz, 1 H), 3.85 (m, 3 H), 3.89 (s, 1 H), 4.01 (m, 1 H), 4.48 (m, 2 H), 4.87 (s, 1 H), 5.31 (d, J = 9.93 Hz, 1H), 6.68 (m, 2 H), 6.80 ( d, J = 8.82 Hz, 2 H), 7.07 (t, J = 6.80 Hz, 2 H), 7.15 (m, 7 H), 7.57 (t, J = 7.72 Hz, 1 H). Example 232 1 H NMR (300 MHz, CDCl 3) δ ppm 0.79 (m, 12 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.05 (dd, J = 8.09 , 5.88 Hz, 1H), 1.26 (m, 1 H), 1.42 (m, 1 H), 1.93 (s, 1 H), 2.55 (s, 3 H), 2.60 (m, J = 3.31 Hz, 1 H), 2.77 (m, 1H), 2.90 (d, J = 7.72 Hz, 2 H), 2.95 (s, 1 H), 3.16 (m, 2 H), 3.57 (s, 1 H), 3.62 (s, 2 H), 3 , 60 (s, 3 H), 3.89 (m, 2 H), 4.07 (m, J = 7.72 Hz, 1 H), 4.48 (s, 2 H), 5.24 (d, J = 8.82 Hz, 1 H), 6.57 (d, J = 4.41 Hz, 2 H), 6.97 (m, 2 H), 7.11 (m, 1 H), 7.17 (m, 4 H), 7.30 (m, 4 H), 7.55 (m, 1 H). Example 233 1 H NMR (300 MHz, CDCl 3) δ ppm 0.77 (m, 12 H), 0.85 (t, J = 7.35 Hz, 3 H), 1.00 (m, 1 H), 1 , 37 (m, 1 H), 1.93 (m, 1 H), 2.34 (s, 3 H), 2.60 (dd, J = 12.69, 3.13 Hz, 1 H), 2.75 (d, J = 10 , 66 Hz, 1 H), 2.82 (s, 3H), 2.87 (t, J = 7.17 Hz, 2 H), 3.07 (s, 1H), 3.23 (m, 3 H), 3.59 (d, J = 9.19 Hz, 2 H), 3.63 (s , 3 H), 3.84 (m, 2 H), 3.94 (m, 1 H), 4.11 (m, J = 8.09 Hz, 1 H), 4.77 (s, 3 H), 5.28 (d, J = 8.82 Hz, 1 H), 6.60 (d, J = 9 , 19 Hz, 1 H), 6.86 (m, 2 H), 6.90 (s, 2 H), 7.02 (d, J = 7.35 Hz, 1 H), 7.13 (s, 1 H), 7.17 (s, 6 H), 7.21 (d, J = 8.09 Hz, 1 H), 7.46 (d, J = 7.72 Hz, 1 H), 7.67 (d, J = 7.72 Hz, 1 H), 8.15 (t, J = 7.91 Hz, 1 H) Example 234 1H NMR (300 MHz, CDCl3) δ ppm 0.76 (d, J = 6.62 Hz, 3 H), 0.79 (s, 9 H), 0.85 (t, J = 7.17 Hz, 3 H), 1.00 (m, 1 H), 1.36 (m, 1 H), 1.91 (m, 1 H), 2.61 (dd, J = 12.50.2.94 Hz, 1H), 2.75 (d, J = 10.66 Hz, 1 H), 2.82 (s, 3H), 2.88 (d, J = 6.99 Hz, 2 H), 3.04 (d, J = 8.46 Hz, 1 H), 3.23 (m, 4 H), 3.58 (s, 1H), 3.62 (s, 3 H), 3.82 (m, 2 H), 3.95 (m, 1 H), 4.12 (m, J = 7.72 Hz, 1 H), 4.76 (s, 2 H), 5.28 (d, J = 10.30 Hz, 1 H), 6, 57 (d, J = 9.19 Hz, 1 H), 6.87 (m, 1 H), 6.92 (m, 2 H), 6.96 (s, 1 H), 7.07 (d, J = 7.72 Hz, 1 H), 7.14 (s, 1 H), 7.29 (m, 7 H), 7.46 (d, J = 7.72 Hz, 1 H), 7.66 (d, J = 7.72 Hz, 1 H), 8.15 (t, J = 7.91 Hz, 1 H). Example 235 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.52 (d, J = 6.62 Hz, 3 H), 0.72 (s, 9 H), 0.77 (t, J = 7 , 54 Hz, 3 H), 0.87 (s, 1H), 0.93 (m, 1 H), 0.98 (d, J = 9.19 Hz, 1 H), 1.30 (m, 1 H), 1.32 ( m, 1H), 1.79 (s, 1 H), 2.52 (s, 3 H), 2.71 (m, 1 H), 2.85 (m, 3 H), 3.11 (m, 2 H), 3.20 (t, J = 9.01 Hz, 1 H), 3.23 (s, 1 H), 3.55 (s, 3 H), 3.70 (s, 1 H), 3.82 (m, J = 11.03 Hz, 2 H), 4.22 (s, 1 H), 4.30 (m, 2 H), 4.33 (d, J = 15.81 Hz, 1 H), 4.52 ( m, 1 H), 7.11 (m, 4 H), 7.18 (m, 2 H), 7.58 (t, J = 6.99 Hz, 1 H), 7.69 (m, 2 H), 7.75 (m, 1 H), 7.90 (s, 1 H), 7.93 (d, J = 8.46 Hz, 1 H), 7.98 (d, J = 8.09 Hz, 1 H), 8.30 (d, J = 8.46 Hz, 1 H). Example 236 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.79 (d, J = 6.25 Hz, 3 H), 0.87 (m, 12 H), 1.01 (m, 1 H) , 1.38 (m, 1 H), 1.87 (m, 1 H), 2.53 (s, 3 H), 2.70 (m, 3 H), 2.77 (d, J = 8.46 Hz, 3 H) , 2.85 (m, 3 H), 3.10 (m, 2 H), 3.11 (m, 2 H), 3.20 (m, 2 H), 3.22 (m, 1 H), 3.65 (s, 3 H), 3.76 (s, 2 H), 3.90 (d, J = 11, 03 Hz, 1 H), 4.04 (s, 2 H), 4.15 (m, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 6.59 (d, J = 3.68 Hz, 1 H), 6.75 (d, J = 3 , 31 Hz, 1 H), 7.14 (m, 7 H), 7.70 (t, J = 7.72 Hz, 1H). Example 237 1H NMR (300 MHz, MeOH-d4) δ ppm 0.86 (d, J = 6.62 Hz, 3 H), 0.91 (t, J = 7.72) Hz, 3 H), 0 , 97 (d, J = 2.94 Hz, 1 H), 1.01 (s, 9 H), 1.06 (m, 1 H), 1.36 (m, 4 H), 1.42 (m, 1H), 1, 49 (m, 2 H), 1.91 (t, J = 14.52 Hz, 1 H), 2.18 (t, J = 6.99 Hz, 2 H), 2.53 (s, 3 H), 2.66 (dd, J = 12.50, 9.56 Hz, 1H), 2.76 (m, 1 H), 2.86 (m, 4 H), 3.11 (m, 2 H), 3.18 (m, 1 H), 3.24 (m, 1 H), 3.55 (m, 2 H), 3.64 (m, 3 H), 3.66 (s, 3 H), 3.74 (d, J = 9.19 Hz, 1 H), 3.90 (s, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.17 (m, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.11 (m, 3 H), 7.17 (m, 4 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 238 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.84 (d, J = 6.62 Hz, 3 H), 0.89 (m, 3 H), 1.00 (s, 9 H) , 1.06 (m, 1 H), 1.33 (s, 1 H), 1.37 (m, 2 H), 1.45 (m, 2 H), 1.59 (m, 2 H), 1.88 (m, 1 H), 2.31 (t, J = 7.54 Hz, 2 H), 2.53 (s, 3 H), 2.67 (m, 4 H), 2.73 (m, 2 H), 2.78 (m, 1 H), 2.85 (m, 2 H), 3.13 (m, 3 H), 3.22 (m, 1 H), 3.65 (s, 3 H), 3.66 (s, 3 H), 3.72 (m, J = 6.99 Hz, 1H), 3.83 (s, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.16 (m, 1 H), 4.35 (d, J = 15.44 Hz, 1 H), 4.53

(m, 1 H), 7.11 (m, 3H), 7.17 (m, 4 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 239 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.84 (d, J = 6.62 Hz, 3 H), 0.88 (m, 3 H), 0.93 (s, 9 H) , 1.04 (m, 1 H), 1.06 (m, 1 H), 1.21 (m, 3 H), 1.40 (m, 1 H), 1.87 (m, 1 H), 2.53 (s, 3 H), 2.59 (c, J = 7.60 Hz, 2 H), 2.75 (m, 4 H), 2.84 (m, 3 H) 1 3.13 (m, 2 H) 1 3.24 (m, 1 H), 3.66 (s, 3 H), 3.74 (d, J = 9, 93 Hz, 1 H), 3.80 (s, 1 H), 3.87 (s, 2 H), 3.93 (d, J = 11.40 Hz, 1 H), 4.14 (m, 1H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1H), 5 , 91 (d, J = 3.31 Hz, 1 H), 6.15 (d, J = 2.94 Hz, 1 H), 7.14 (m, 7 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 240 1 H NMR (300 MHz, MeOH-Cl 4) δ ppm 0.71 (d, J = 6.62 Hz, 3 H), 0.79 (s, 9 H), 0.84 (m, 3 H) , 0.90 (m, 2 H), 0.98 (s, 1 H), 1.01 (m, 1 H), 1.36 (m, 1 H), 1.88 (m, J = 14.34 Hz, 1H), 2 , 52 (s, 3 H), 2.70 (m, 1 H), 2.79 (m, 2 H), 2.87 (m, 2 H), 3.10 (m, 2 H), 3.22 (t, J = 9.38 Hz, 1 H), 3.58 (s, 3 H), 3.67 (d, J = 15.08 Hz, 1 H), 3.85 (s, 1 H), 3.89 (d, J = 11.40 Hz, 1 H), 3.98 (m, 2 H), 4.25 (s, 1 H), 4.35 (m, 1 H), 4.52 (m, 1 H), 7.12 (m, 4 H), 7.19 (m, 3 H), 7.48 (d, J = 8.46 Hz, 2 H), 7.56 (m, 3 H), 7.69 (t, J = 7.72 Hz, 1 H), 7.80 (m, 1 H), 8, 10 (s, 1 H). Example 241 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.85 (d, J = 6.62 Hz, 3 H), 0.89 (m, 12 H), 1.00 (s, 9 H) , 1.07 (m, 1 H), 1.41 (m, 3 H), 1.91 (m, 1 H), 2.53 (s, 3 H), 2.69 (m, 4 H), 2.77 (m, 3 H), 2.84 (dd, J = 9.56, 4.04 Hz, 2 H), 3.11 (m, 2 H), 3.16 (m, 1 H), 3.22 (m, 1 H), 3.66 (s, 3 H), 3.72 (s, 1 H), 3.84 (s, 1 H), 3.94 (d, J = 11.03 Hz, 1 H), 4.15 (m, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.12 (m, 3 H), 7.17 (m, 4 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 242 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.71 (d, J = 6.25 Hz, 3 H), 0.80 (s, 9 H), 0.85 (t, J = 7 , 35 Hz, 3 H), 0.97 (d, J = 5.88 Hz, 1 H), 1.02 (m, 1 H), 1.35 (m, 1 H), 1.88 (m, 1 H), 2.10 (s, 3 H), 2.53 (s, 3 H), 2.68 (m, 2 H), 2.76 (m, 2 H), 2.85 (m, 3 H), 3.11 (m, 2 H), 3.22 (t, J = 8.82 Hz, 1 H), 3.64 (s, 3 H), 3.72 (s, 1 H), 3.80 (d, J = 16.55 Hz, 1 H), 3.88 (m, 3 H), 4.18 (m, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.11 (m, 4 H), 7.17 (m, 4 H), 7.32 (d, J = 8.82 Hz, 2 H), 7.48 (d, J = 8.46 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 243 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.70 (d, J = 6.62 Hz, 3 H), 0.76 (s, 9 H), 0.85 (t, J = 7 , 35 Hz, 3 H), 0.99 (m, 1 H), 1.36 (m, 1 H), 1.85 (m, 1 H), 2.53 (s, 3 H), 2.71 (m, 1 H), 2.78 (m, 2 H), 2.83 (d, J = 4.04 Hz; 1H), 2.88 (m, 2 H), 3.11 (m, 3 H), 3.22 (t, J = 8.64 Hz, 1H), 3.28 (s, 1 H), 3.63 (s, 3 H), 3.68 (s, 1 H), 3.82 (s, 1 H), 3.86 (s, 1 H), 3.89 (s, 3 H), 4.01 (m, 2 H) 1 4.22 (m, 1 H), 4.34 (d, J = 15.44 Hz, 1 H), 4.53 (m, 1 H), 7.11 (m, 3 H), 7.18 (m, 4 H), 7.53 (d, J = 8.46 Hz, 2 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.92 (d, J = 8.09 Hz, 2 H) . Example 244 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (s, 12 H), 0.88 (m, 3 H), 1.03 (m, 1 H), 1.44 (m, 1 H ), 2.04 (m, 4 H), 2.54 (s, 3 H), 2.61 (s, 1H), 2.89 (d, J = 6.99 Hz, 4 H), 3.17 (d, J = 6.62 Hz, 3 H), 3.65 (m, 2 H), 3.94 (s, 3 H), 4.10 (d, J = 7.35 Hz, 1 H), 4.47 (s, 2 H), 5.26 (s, 1 H), 6.64 (s, 2 H), 6.91 (s, 1 H), 7.02 (t, J = 8.46 Hz, 2 H), 7.13 (dd, J = 14.71, 7.35 Hz, 10 H), 7.35 (m, 3 H), 7.55 (t, J = 7.54 Hz, 1 H). Example 245 1 H NMR (300 MHz, CDCl 3) δ ppm 0.82 (m, 12 H), 0.88 (m, 3 H), 1.03 (m, 1 H), 1.42 (m, 1 H ), 1.94 (m, 1 H), 2.53 (s, 3 H), 2.58 (d, J = 2.57 Hz, 1 H), 2.75 (d, J = 4.78 Hz, 1H), 2.91 ( t, J = 8.09 Hz, 3 H), 3.16 (m, 3 H), 3.62 (m, 1H), 3.61 (s, 3 H), 3.81 (m, 3 H), 3.88 (s, 1H), 3.92 (d, J = 11.03 Hz, 1 H ), 4.05 (m, 1 H), 4.47 (s, 3 H), 4.75 (s, 1 H), 5.27 (d, J = 8.82 Hz, 1 H), 6.58 (s, 2 H), 6.82 (d, J = 8.09 Hz, 1 H), 6.89 (m, 3 H), 6.96 (m, 3 H), 7.05 (m, 2 H), 7.16 (d, J = 6.62 Hz, 4 H), 7.22 (m, 2 H), 7.53 (t, J = 7.72 Hz, 1 H). Example 246 1H NMR (300 MHz, MeOH-d4) δ ppm 0.72 (d, J = 6.62 Hz, 3 H), 0.73 (s, 9 H), 0.86 (t, J = 7 , 35 Hz, 3 H), 0.99 (m, 1 H), 1.29 (s, 9 H), 1.37 (m, 1 H), 1.86 (m, 1 H), 2.53 (s, 3 H), 2.67 (dd, J = 12.50, 3.31 Hz, 1 H), 2.77 (m, 1 H), 2.84 (m, 1 H), 3.09 (m, 1 H), 3.16 (m, 1 H), 3.24 (m, 1 H), 3.65 (s, 3 H), 3.67 (m, 1 H), 3.79 (d, J = 8.82 Hz, 1 H), 3.88 (d, J = 10.66 Hz, 1 H), 3.90 (s, 3H), 4.17 (m, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (d, J = 15.81 Hz, 1 H), 7.14 (m, 10 H), 7.31 (m, 5 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 247 1H NMR (300 MHz, MeOH-d4) δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.81 (s, 9 H), 0.87 (t, J = 7 , 17 Hz, 3 H), 1.01 (m, 1 H), 1.38 (m, 1 H), 1.87 (m, 1 H), 2.53 (s, 3 H), 2.64 (dd, J = 12, 32, 3.13 Hz, 1 H), 2.73 (m, 2 H), 2.82 (m, 2 H), 3.12 (m, 4 H), 3.20 (d, J = 9.56 Hz, 1 H), 3.25 (s, 1 H), 3.65 (s, 3 H), 3.73 (m, 1 H), 3.75 (s, 1 H), 3.80 (d, J = 4.04 Hz, 2 H), 3.89 (d, J = 11.03 Hz, 1 H), 4.15 (m, 4 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 6.71 (d, J = 8.46 Hz, 1 H), 6.81 (m, 1 H), 6.89 (d, J = 2.21 Hz, 1H), 7.14 (m, 7 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 248 1H NMR (300 MHz, MeOH-d4) δ ppm 0.71 (s, 9 H), 0.74 (d, J = 6.62 Hz, 3 H), 0.86 (t, J = 7 , 17 Hz, 3 H), 1.01 (m, 1 H), 1.37 (m, 1 H), 1.87 (m, 1H), 2.53 (s, 3 H), 2.73 (m, 1 H), 2 , 80 (m, 2 H), 2.87 (m, 2 H), 3.11 (m, 3 H), 3.22 (t, J = 9.01 Hz, 1 H), 3.26 (m, 1 H), 3.64 (s, 3 H), 3.67 (s, 1 H), 3.82 (s, 1 H), 3.89 (d, J = 11.03 Hz, 1H), 4.02 (m, 2 H), 4.24 (m, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.14 (m, 7 H) , 7.58 (m, 4 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 249 1H NMR (300 MHz, MeOH-d4) δ ppm 0.87 (c, J = 6.86 Hz, 9 H), 1.00 (s, 9 H), 1.11 (m, 1 H) , 1.28 (m, 2 H), 1.33 (m, 2 H), 1.39 (m, 1 H), 1.43 (d, J = 2.94 Hz, 1 H), 1.53 (m, 2 H), 1.60 (s, 3 H), 1.68 (m, 3 H), 1.88 (d, J = 14.34 Hz, 2 H), 1.94 (m, 2 H), 2.53 (s, 3 H), 2.67 (d, J = 6.99 Hz, 2 H), 2.75 ( t, J = 7.35 Hz, 3 H), 2.85 (m, 2 H), 3.14 (m, 2 H), 3.22 (m, 1 H), 3.65 (s, 3 H), 3.73 (s, 1 H), 3.84 (s, 1H), 3.94 ( d, J = 11.03 Hz, 1 H), 4.15 (m, 1 H), 4.35 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 5.10 (m, 1 H), 7.15 (m, 7 H), 7.70 (t, J = 7, 72 Hz, 1 H). Example 250 1 H NMR (300 MHz, MeOH-d4) δ ppm 0.13 (m, 3 H), 0.47 (m, 3 H), 0.84 (d, J = 6.62 Hz, 3 H) , 0.88 (m, 3 H), 0.99 (s, 9 H), 1.40 (m, 1 H), 1.89 (m, 1H), 2.52 (d, J = 3.31 Hz, 3 H), 2 , 73 (m, 5 H), 2.86 (m, 3 H), 3.17 (m, 5 H), 3.66 (s, 3 H), 3.74 (s, 1 H), 3.87 (s, 1 H), 3.94 (d, J = 11.40 Hz, 1 H), 4.17 (m, 1 H), 4.35 (d, J = 15.44 Hz, 1 H), 4.53 (m, 1 H), 7.14 (m, 7 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 251 1H NMR (300 MHz, MeOH-d4) δ ppm 0.75 (d, J = 6.62 Hz, 3 H), 0.86 (d, J = 10.66 Hz, 12 H), 1, 00 (m, 1 H), 1.27 (t, J = 7.72 Hz, 3 H), 1.36 (dd, J = 6.62, 3.68 Hz, 1 H), 1.86 (m, 1H), 2.53 (s, 3 H), 2.67 (c, J = 7.72 Hz, 5 H), 2.82 (m, 3 H), 2.87 (m, 1 H), 3.13 (m, 3 H), 3.22 (t, J = 9.01 Hz, 1 H), 3.66 (s, 3 H), 3.76 (s, 1 H), 3.79 (s, 1 H), 3.89 (m, 3 H), 4.20 (s, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 6.78 (s, 1 H), 7.15 (m, 8 H), 7.69 (t, J = 7.72 Hz, 1 H). Example 252 1H NMR (300 MHz, MeOH-d4) δ ppm 0.73 (d, J = 6.62 Hz, 3 H), 0.80 (s, 9 H), 0.86 (t, J = 7 , 35 Hz, 3 H), 1.01 (m, 1 H), 1.38 (m, 1 H), 1.84 (d, J = 11.03 Hz, 1 H), 2.53 (s, 3 H), 2.67 (m, 2 H), 2.75 (dd, J = 13.05, 3.49 Hz, 2 H), 2.84 (m, 2 H), 3.12 (m, 4 H), 3.22 (t, J = 8.82 Hz, 1 H), 3.64 (s, 3 H), 3.72 (s, 1 H), 3.78 (s, 1 H), 3.83 (d, J = 7.35

Hz, 2 H), 3.89 (m, 1 H), 4.18 (m, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.49 (m, 3 H), 4.54 (d, J = 9.19 Hz, 1 H), 6.60 (d, J = 8.09 Hz, 1 H), 7.04 (dd, J = 8.09, 1.84 Hz, 1 H), 7.15 (m, 8 H), 7.26 (s, 1 H) , 7.70 (t, J = 7.72 Hz, 1 H). Example 253 1 H NMR (300 MHz, CDCl 3) δ ppm 0.77 (d, J = 6.62 Hz, 3 H), 0.78 (d, J = 2.94 Hz, 9 H), 0.85 ( s, 1H), 0.87 (t, J = 7.35 Hz, 3 H), 1.05 (m, 1 H), 1.43 (m, 1 H), 1.94 (s, 1 H), 2.53 (d, J = 4.78 Hz, 3 H), 2.57 (s, 1 H), 2.60 (m, 1 H), 2.76 (m, 1 H), 2.93 (m, 3 H), 2.98 (m, 1 H), 3.16 (m, 3 H), 3.61 (m, 5 H), 3.81 (m, 1 H), 3.87 (m, 2 H), 3.90 (d, J = 11.03 Hz, 1 H), 4.06 (d, J = 8.82 Hz, 1 H), 4.76 (s, 1 H), 5.23 (d, J = 8.09 Hz, 1H), 6.61 (s, 2 H), 7.07 (m, 3 H), 7.15 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 254 1H NMR (300 MHz, CDCl3) δ ppm 0.78 (s, 9 H), 0.81 (d, J = 6.62 Hz, 3 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.03 (m, 1 H), 1.42 (m, 1 H), 1.95 (s, 1 H), 2.53 (d, J = 4.78 Hz, 3 H), 2.59 (m, 2 H), 2.78 (dd, J = 12.69, 10.11 Hz, 1H), 2.90 (d, J = 7.35 Hz, 3 H), 3.16 (m, 3 H), 3.59 (s, 1 H), 3.62 (s, 3 H), 3.85 (s, 3 H), 3.87 (s, 3 H), 3.92 (m, 1 H), 4.08 (d, J = 9.19 Hz, 1 H), 4.47 (m, 2 H), 4.81 (s, 1 H), 5.30 (s, 1 H), 6.47 (s, 1 H), 6.56 (d, J = 9.56 Hz, 1 H), 6.76 (s, 2 H), 6.97 (s, 1 H), 7.04 (m, 1 H), 7.10 (m, 1 H), 7.11 (m, 2 H), 7.18 (m, 4 H), 7.54 (t, J = 7.72 Hz, 1H). Example 255 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (m, 3 H), 0.81 (s, 9 H), 0.87 (t, J = 7.54 Hz, 3 H), 1 , 02 (m, 1 H), 1.41 (m, 1 H), 1.91 (s, 1 H), 2.54 (s, 3 H), 2.59 (m, 1 H), 2.75 (m, 1 H), 2.93 (m, 2 H), 3.18 (m, 3 H), 3.56 (s, 1 H), 3.60 (s, 3 H), 3.64 (s, 1 H), 3.82 (d, J = 4.41 Hz, 2 H), 3.86 (s, 3 H), 3.91 (d, J = 11.03 Hz, 1 H), 4.07 (s, 1 H), 4.47 (s, 2 H), 4.75 (s, 1 H), 5.27 (m, 1 H), 6.61 (s, 2 H), 6.89 (m, 1 H), 7.03 (m, 3 H), 7.11 (m, 2 H), 7.18 (m, 4 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 256 1 H NMR (300 MHz, CDCl 3) δ ppm 0.85 (m, 15 H), 1.07 (m, 1 H), 1.42 (m, 1 H), 2.00 (m, 1 H) , 2.55 (m, 2 H), 2.54 (m, 3 H), 2.75 (dd, J = 12.32, 10.11 Hz, 1H), 2.92 (m, 3 H), 3.17 (m, 3 H), 3.56 (d, J = 11.03 Hz, 1 H), 3.61 (s, 3 H), 3.65 (s, 1 H), 3.81 (d, J = 4.78 Hz, 2 H), 3.92 (d, J = 11.03 Hz, 1 H) , 4.06 (d, J = 8.46 Hz, 1H), 4.47 (s, 2 H), 4.73 (s, 1 H), 5.26 (d, J = 8.09 Hz, 1 H), 5.93 (m, 2 H), 6.58 (d, J = 2.21 Hz, 2 H), 6.83 (s, 1 H), 7.06 (dd, J = 11.40, 7.72 Hz, 2 H), 7.15 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 257 1 H NMR (300 MHz, CDCl 3) δ ppm 0.80 (d, J = 6.25 Hz, 3 H), 0.83 (s, 9 H), 0.89 (m, 3 H), 1 , 02 (m, 1H), 1.43 (s, 1 H), 1.96 (s, 1 H), 2.17 (s, 3 H), 2.50 (s, 1H), 2.54 (s, 3 H), 2 , 74 (m, 1 H), 2.89 (d, J = 7.72 Hz, 3 H), 3.17 (m, 2 H), 3.55 (d, J = 9.56 Hz, 1 H), 3.62 (m, 3 H), 3.63 (s, 1 H), 3.81 (s, 3 H) , 3.83 (d, J = 5.88 Hz, 2 H), 3.91 (d, J = 11.40 Hz, 1 H), 4.05 (s, 1 H), 4.47 (s, 2 H), 4.73 (s, 1 H), 5.30 (s, 1 H), 6 , 47 (s, 1 H), 6.51 (s, 1 H), 6.75 (d, J = 8.46 Hz, 1 H), 7.06 (dd, J = 13.97, 6.99 Hz, 4 H), 7.15 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 HOUR). Example 258 1 H NMR (300 MHz, CDCl 3) δ ppm 0.78 (s, 9 H), 0.81 (m, 3 H), 0.87 (t, J = 7.35 Hz, 3 H), 1 , 03 (m, 1 H), 1.41 (s, 1 H), 1.91 (s, 1 H), 2.54 (s, 3 H), 2.77 (dd, J = 12.69, 10.11 Hz, 1 H) , 2.90 (d, J = 7.72 Hz, 2 H), 3.14 (m, 2 H), 3.22 (m, 1 H), 3.60 (s, 2 H), 3.61 (s, 3 H), 3.82 (m, 2 H), 3.88 (s, 3 H), 3.91 (m, 1 H), 4.07 (d, J = 8.09 Hz, 1 H), 4.47 (d, J = 2.57 Hz, 2 H), 4.80 (s, 1 H), 5.25 (d, J = 9.56 Hz, 1 H), 5.60 (s, 1 H), 6.48 (s, 1 H), 6.54 (s, 1 H), 6.66 (dd, J = 8.09, 1.84 Hz, 1H), 6.79 (d, J = 8.09 Hz, 1 H), 7.00 (d, J = 1.47 Hz, 1 H), 7, 03 (d, J = 7.72 Hz, 1 H), 7.07 (d, J = 7.35 Hz, 1H), 7.15 (m, 5 H), 7.54 (t, J = 7.72 Hz, 1 H). Example 259 1H NMR (300 MHz, CD3OD) δ ppm 0.73 (m, 3 H), 0.75 (s, 9 H), 0.86 (t, J = 7.17 Hz, 3 H), 1 , 06 (t, J = 7.17 Hz, 1 H), 1.36 (m, 1 H), 1.87 (s, 1 H), 2.53 (s, 3 H), 2.69 (m, 1 H), 2 , 82 (m, 3 H), 2.87 (m, 2 H), 3.08 (s, 3 H), 3.13 (m, 3 H), 3.22 (t, J = 8.82 Hz, 1 H), 3.64 (s, 3 H), 3.66 (d, J = 3.31 Hz, 1 H), 3.84 (d, J = 4.04 Hz, 1 H), 3.90 (d, J = 11.03 Hz, 1 H), 4.05 (s, 2 H), 4.27 (s, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 7.11 (m, 4 H), 7.15 (s, 1 H), 7.19 (m, 3 H), 7.70 (m, 3 H), 7.86 (d, J = 8.46 Hz, 2 H). Example 260 1H NMR (300 MHz, CD3OD) δ ppm 0.74 (d, J = 6.62 Hz, 3 H), 0.84 (s, 9 H), 0.87 (m, 3 H), 0 , 94 (s, 1 H), 1.00 (m, 1 H), 1.37 (m, 1 H), 1.83 (d, J = 11.03 Hz, 1 H), 1.84 (m, 1 H), 2.53 (s, 3 H), 2.67 (m, 1 H), 2.76 (dd, J = 9.93, 5.88 Hz, 3 H), 2.86 (m, 1 H), 3.09 (m, 1 H), 3.15 (m, 1 H), 3.25 (m, 1 H), 3.65 (s, 3 H), 3.74 (s, 1 H), 3.80 (s, 1 H), 3.88 (d, J = 11.40 Hz, 1 H), 4.02 (s, 2 H), 4.27 (d, J = 8.46 Hz, 1 H), 4.34 (d, J = 15.81 Hz, 1 H), 4.53 (m, 1 H), 6.96 (s, 1 H), 7.12 (m, 5 H), 7.18 (m, 4 H), 7.69 (t, J = I.12 Hz, 1H). Example 261 1H NMR (300 MHz, CD3OD) δ ppm 0.87 (m, 6 H), 1.00 (s, 9 H), 1.05 (d, J = 8.82 Hz, 1 H), 1 , 29 (s, 1 H), 1.40 (m, 4 H), 1.50 (m, 5 H), 1.90 (m, 1H), 2.53 (s, 3 H), 2.71 (m, 3 H), 2 , 80 (m, 1 H), 2.86 (m, 1 H), 3.13 (m, 2 H), 3.22 (m, 1 H), 3.53 (t, J = 6.43 Hz, 1 H), 3.65 (s, 1 H), 3.65 (d, J = 4.04 Hz, 3 H), 3.75 (s, 1 H), 3.84 (m, 1 H), 3.93 (m, 1 H) 4.17 (m, 1 H), 4.34 (m, 1 H), 4.54 (m, 1 H), 7.11 (dd, J = 4.96.2.02 Hz, 5 H), 7.17 (m, 3 H), 7.70 (t, J = 7.72 Hz, 1 H), 7.86 (d, J = 9.56 Hz, 1 H). Example 262 1H NMR (300 MHz, CD3OD) δ ppm 0.84 (m, 3 H), 0.89 (m, 3 H), 0.91 (s, 1 H), 0.93 (s, 9 H ), 1.04 (m, 1 H), 1.40 (m, 1 H), 1.87 (s, 3 H), 1.92 (s, 1 H), 2.13 (s, 3 H), 2.53 (s, 3 H), 2.69 (m, 3 H), 2.77 (s, 1 H), 2.84 (m, 2 H), 3.13 (m, 2H), 3.17 (m, 1 H), 3.24 (m, 1 H), 3.66 (s, 3 H), 3.72 (s, 1 H), 3 , 80 (m, 3 H), 3.93 (d, J = 11.40 Hz, 1 H), 4.15 (m, 1 H), 4.35 (d, J = 15.44 Hz, 1 H), 4.53 (m, 1H), 6.02 (s, 1H), 7.11 (m, 6 H ), 7.18 (m, 1 H), 7.70 (t, J = 7.72 Hz, 1 H). Example 263 1 H NMR (300 MHz, CDCl 3), δ ppm 0.84 (m, 15 H), 1.03 (m, 2 H), 1.35 (m, 2 H), 1.91 (m, 1 H), 2.61 (m, 3 H), 2.77 (m, 1 H), 2.91 (d, J = 7.72 Hz, 2 H), 2.98 (m, J = 9.19 Hz, 1 H), 3.19 (m, 3 H), 3.62 (m, 4 H), 3.89 (t, J = 11.03 Hz, 3 H), 4.06 (c, J = 7.72 Hz, 1 H), 4.53 (sa, 2 H), 5.25 (d, J = 9.56 Hz, 1 H), 6.66 (s, 2 H), 7.20 (m, 11 H), 7.61 (s, 1 H). Example 264 1H NMR (300 MHz, CDCl3), δ ppm 0.83 (m, 15 H), 1.03 (m, 2 H), 1.36 (m, 2 H), 1.96 (m, 1H ), 2.27 (s, 6 H), 2.53 (m, 4 H), 2.76 (dd, J = 12.50.10.30 Hz, 1 H), 2.91 (m, 3 H), 3.16 (m, 3 H), 3.59 (m, 4 H), 3.86 (m, 3 H), 4.06 (m, 1 H), 4.50 (sa, 2 H), 5.29 (d, J = 9.19 Hz, 1 H), 6.53 (m, 2 H), 6.90 (m, 3 H), 7.14 (m, 7 H), 7.57 (m, 1 H). Example 265 1 H NMR (300 MHz, CDCl 3), δ ppm 0.96 (m, 24 H), 1.40 (m, 1 H), 1.54 (m, 1 H), 1.96 (s, 1 H), 2.52 (m, 6 H), 2.82 (m, 4 H), 3.14 (m, 3 H), 3.49 (d, J = 9.56 Hz, 1 H), 3.66 (m, 4 H), 3.87 (d, J = 11.03 Hz, 1 H), 4.09 (m, 1 H), 4.47 (m, 2H), 4.72 (s, 1 H), 5.33 (d, J = 9.93 Hz, 1 H), 6.47 (d, J = 9.56 Hz, 1 H), 6.70 (s, 1 H), 7.11 (m, 7H), 7.53 (t, J = 7.72 Hz, 1 H). Example 266 1 H NMR (300 MHz, CDCl 3), δ ppm 0.93 (m, 27 H), 1.32 (m, 2 H), 1.94 (m, J = 8.82 Hz, 1 H), 2.56 (m, 5

H), 2.90 (m, 4 H), 3.16 (m, 3 H), 3.60 (m, J = 7.72 Hz, 4 H), 3.77 (dd, J = 9, 74, 4.96 Hz, 1 H), 3.98 (m, 2 H), 4.47 (m, 2 H), 4.73 (s, 0.5 H), 4.92 (s, 0.5 H), 5.30 (s, 1 H), 6.57 (m, 1 H), 6, 65 (s, 0.5 H), 6.91 (s, 0.5 H), 7.11 (m, 7 H), 7.55 (t, J = 7.54 Hz, 1 H). Example 267 1H NMR (300 MHz, CDCl3), δ ppm 0.77 (m, 12 H), 0.87 (t, J = 7.35 Hz, 3 H), 1.05 (m, 1H), 1 , 43 (m, 1 H), 1.91 (s, 1 H), 2.55 (s, 3 H), 2.65 (dd, J = 12.50, 4.04 Hz, 1 H), 2.77 (m, 1 H) , 2.92 (d, J = 7.72 Hz, 2 H), 3.01 (t, J = 8.82 Hz, 1 H), 3.17 (m, 3 H), 3.60 (m, 5 H), 3.91 (m, 3 H), 4.06 (m, 1 H), 4 , 48 (s, 2 H), 4.84 (sa, 1 H), 5.21 (d, J = 8.82 Hz, 1 H), 6.69 (d, J = 8.82 Hz, 1 H), 6.82 (sa, 1 H), 7.06 (m, 2 H), 7.15 ( m; 5 H), 7.54 (m, 5 H). Example 268 1 H NMR (300 MHz, CDCl 3), δ ppm 0.87 (m, 6 H), 1.06 (m, 15 H), 1.44 (m, 1 H), 1.55 (m, 2 H), 1.76 (m, 4 H), 1.93 (m, 1 H), 2.54 (m, 4 H), 2.67 (m, 1 H), 2.92 (m, 2 H), 3.05 (m, 1 H), 3.18 (m, 3 H), 3.56 (s, 3 H), 3.80 (d, J = 9.56 Hz, 1 H), 3.96 (m, J = 11.03 Hz, 2 H), 4.48 (m, 2 H), 4.87 (s, 1 H), 5.31 ( m, 1 H), 6.68 (s, 1 H), 6.95 (s, 1 H), 7.12 (m, 7 H), 7.56 (t, J = 7.54 Hz, 1H). Example 269 1 H NMR (300 MHz, CDCl 3), δ ppm 0.81 (m, 15 H), 1.04 (m, 1 H), 1.43 (m, 1 H), 1.92 (m, 1 H), 2.59 (m, 4 H), 2.76 (m, 1 H), 2.92 (d, J = 7.72 Hz, 2 H), 3.02 (t, J = 8.64 Hz, 1 H), 3.17 (m, 3 H), 3.62 (m, 5 H), 3.82 (s, 2 H), 3.92 (d, J = 11.03 Hz, 1 H), 4.03 (c, J = 8.21 Hz, 1 H), 4.48 (m, 2 H), 4.82 (s, 1 H), 5.24 (d, J = 9.10 Hz, 1 H), 6.68 (d, J = 7.72 Hz, 1 H), 6.79 (s, 1 H), 7.15 (m, 8 H), 7.39 (m, 2 H), 7.55 (t, J = 7 , 72 Hz, 1 H). Example 276 1H NMR (300 MHz, CD3OD) δ ppm 0.73 (s, 9 H), 0.79 (d, J = 8.82 Hz, 2 H), 0.89 (s, 9 H), 0 , 98 (m, 1 H), 2.34 (d, J = 9.56 Hz, 1 H), 2.83 (m, 5 H), 3.11 (m, 2 H), 3.26 (m, 1 H), 3.46 (s, 3 H), 3.60 (s, 3 H), 3.70 (s, 1H), 3.84 (s, 1 H), 4.02 (m, 2 H), 4.19 (s, 1 H), 4.45 (m, 2 H), 4.71 (s, 2 H), 7.06 (m, 3 H), 7.16 (m, 2 H), 7.37 (s, 1 H), 7.45 (d, J = 4.78 Hz, 2 H), 7.61 (m, 1H), 7.96 (s, 1 H), 9.11 (s, 2 H), 9.13 (d, J = 3.68 Hz, 1 H). Example 277 1H NMR (300 MHz, CD3OD) δ ppm 0.86 (s, 9 H), 0.92 (s, 9 H), 2.36 (m, 2 H), 2.51 (s, 3 H ), 2.83 (m, 5 H), 3.10 (m, 3 H), 3.26 (d, J = 3.31 Hz, 1 H), 3.46 (s, 3 H), 3.62 (s, 3 H), 3.76 (s, 1 H), 3.86 (s, 1 H), 4.05 (s, 1 H), 4.14 (m, 3 H), 4.46 (m, 2 H), 4.71 (s, 2 H), 6.67 (s, 1H), 7.07 (m, 3 H), 7 , 16 (m, 2 H), 7.38 (s, 1 H), 7.67 (s, 1 H). Example 278 1H NMR (300 MHz, CD3OD) δ ppm 0.87 (s, 9 H), 0.93 (m, 9 H), 2.36 (d, J = 9.56 Hz, 1 H), 2 , 85 (m, 6 H), 3.12 (m, 3 H), 3.28 (m, 2 H), 3.46 (s, 3 H), 3.62 (s, 3 H), 3.78 (s, 1 H), 3.86 (s, 1 H), 4.05 (s, 1H), 4.15 (d, J = 16.18 Hz, 2 H), 4.46 (m, 2 H), 4.71 (s, 2 H), 7.07 (m, 2 H), 7.16 (m, 2 H), 7.38 ( s, 1 H), 7.44 (dd, J = 6.62, 4.78 Hz, 1 H), 7.62 (s, 1 H), 7.91 (m, 2 H), 8.19 (d, J = 8.09 Hz, 1 H), 8.57 (d, J = 4.41 Hz, 1 HOUR). Example 279 1H NMR (300 MHz, DMSO-d6) δ ppm 0.95 (s, 9H), 0.86 (s, 9H), 1.30-1.27 (d, J = 6.62 Hz, 6H ), 2.46 (m, 1H), 2.77-2.63 (m, 4H), 3.26-2.96 (m, 5H), 3.38 (s, 2H), 3.53 (s, 3H), 3.62 (m, 1H), 3.71-3.68 (d, J = 9.19 Hz, 1H), 4.02 (s, 3H), 4.09 (s, 1H), 4.46-4.27 (dd, J = 15.44, 40.08 Hz, 2H), 4.68 (s, 2H) , 4.79-4.78 (d, J = 3.31 Hz, 1H), 7.137.01 (m, 5H), 7.31 (s, 1H), 7.43 (s, 1H), 7, 65-7.62 (d, J = 9.2 Hz, 1H), 9.19 (s, 1H). Example 281 1 H NMR (300 MHz, DMSO-d6), δ ppm 0.68 (m, 12 H), 0.79 (t, J = 7.17 Hz, 3 H), 0.92 (m, 1 H ), 1.28 (s, 1 H), 1.83 (m, 1 H), 2.70 (m, 4 H), 3.07 (m, 2 H), 3.17 (s, 1 H), 3.35 (m, 3 H), 3.52 (d, J = 6.62 Hz, 4 H), 3.71 (m, 10 H), 3.89 (m, 2 H), 3.95 (d, J = 11.03 Hz, 1 H), 4.07 (s, 1 H), 4.36 (m, 2 H), 6.78 (m, 2 H), 6.95 (d, J = 9.56 Hz, 1 H), 7.03 (d, J = 8.82 Hz, 1 H), 7.09 (m, 4 H), 7.19 (m, 1 H), 7.38 (d, J = 9.19 Hz, 1 H) , 7.42 (s, 1 H), 9.02 (s, 1 H). Example 282 1 H NMR (500 MHz, DMSO-d6), δ ppm 0.64 (d, J = 6.10 Hz, 3 H), 0.68 (s, 9 H), 0.76 (m, 3 H ), 0.89 (m, 2 H), 1.26 (m, 2 H), 1.49 (s, 1 H), 1.74 (m, 1 H), 2.00 (d, J = 14.04 Hz, 1 H), 2.14 (d, J = 4.88 Hz, 6 H), 3.38 (m, 3 H), 3.48 (s, 1 H), 3.52 (s, 3 H), 3.56 (s, 1 H), 3.68 (m, 2 H), 3.81 (d, J = 6.10 Hz, 2 H), 3.86 (m, 1 H), 3.91 (d, J = 10.99 Hz, 1 H), 4.00 (d, J = 4.88 Hz, 1 H), 4.09 (s, 1 H), 4.32 (d, J = 15.26 Hz, 1 H), 4.41 (m, 1 H), 4.63 (d, J = 16.48 Hz, 2 H), 6.89 (d, J = 9.77 Hz, 1 H), 6.99 (d, J = 5.49 Hz, 1 H), 7.06 (s, 1 H), 7.09 (m, 5 H), 7.15 (dd, J = 15.56, 7.02 Hz, 1H), 7.22 (m, 1 H), 7.35 (d, J = 9.16 Hz, 1 H), 8.99 (s, 1 H). Example 283 1 H NMR (300 MHz, CDCl 3) δ ppm 0.67 (d, J = 6.62 Hz, 3 H), 0.79 (m, 6 H), 0.87 (t, J = 7.35 Hz, 3 H), 0.93 (dd, J = 7.1 7, 2.39 Hz, 1 H), 1.04 (m, 1 H), 1.27 (m, 1 H), 1.42 (m, 1 H ), 1.64 (m, 2 H), 1.94 (d, J = 11.40 Hz, 1 H), 2.53 (m, 3 H), 2.77 (m, 1 H), 2.93 (m, 3 H), 3.16 (m, 4 H), 3.59 (s, 1 H), 3.61 (s, 3 H), 3.77 (s, 1 H), 3.78 (s, 3 H), 3.79 (m, 1 H), 3.87 (t, J = 5.70 Hz, 1 H), 3.92 (d, J = 2.57 Hz, 1 H), 4.08 (d, J = 8.46 Hz, 1 H), 4.49 (s, 2 H), 4.72 (s, 1 H), 5.08 (s, 1H), 6.58 (d, J = 13.97 Hz, 2 H), 6.83 (m, 2 H), 7.12 (m, 7 H), 7 , 20 (d, J = 8.82 Hz, 2 H), 7.58 (m, 1 H). Example 284 1H NMR (300 MHz, CDCl3) δ ppm 0.82 (d, J = 6.62 Hz, 6 H), 0.89 (m, 12 H), 1.09 (m, 2 H), 1 , 30 (m, 2 H), 1.45 (m, 2 H), 1.82 (m, 1 H), 1.97 (s, 1 H), 2.51 (d, J = 4.41 Hz, 1H), 2 , 55 (s, 3 H), 2.69 (m, 3 H), 2.93 (d, J = 7.72 Hz, 2 H), 3.08 (s, 1 H), 3.19 (m, 3 H), 3.58 (s, 3 H), 3.61 (s, 1 H), 3.83 ( m, 1 H), 3.95 (d, J = 11.03 Hz, 1 H), 4.01 (d, J = 8.09 Hz, 1 H), 4.49 (s, 2 H), 4.82 (s, 1 H), 5.16 (s, 1 H), 6.76 (d, J = 8.46 Hz, 1 H), 6.86 (s, 1 H), 7.05 (d, J = 8.09 Hz, 1 H), 7.10 (d, J = 3.68 Hz, 1 H), 7.17 (m, 5 H), 7.58 (m, 1 H). Example 285 1 H NMR (300 MHz, CDCl 3) δ ppm 0.64 (d, J = 6.62 Hz, 3 H), 0.74 (t, J = 7.35 Hz, 3 H), 0.79 ( d, J = 6.62 Hz, 3 H), 0.85 (m, 3 H), 1.29 (s, 1 H), 1.40 (s, 1 H), 1.92 (s, 1 H), 2.54 ( s, 3 H), 2.61 (d, J = 13.97 Hz, 1 H), 2.81 (d, J = 9.93 Hz, 1 H), 2.91 (m, 3 H), 3.16 (m, 4 H), 3.59 (s, 3 H), 3.62 (s, 1 H), 3.70 (t, J = 8.09 Hz, 1 H), 3.93 (m, 3 H), 4.09 (d, J = 8.82 Hz, 2 H), 4.48 (s, 2 H), 4.80 (s, 1 H), 5.07 (s, 1 H), 6.60 (s, 1 H), 6.74 (s, 1 H), 7.13 (m, 8 H), 7.41 (d, J = 8.09 Hz, 2 H), 7.55 (t, J = 7.54 Hz, 1 H), 7.73 (m, 2 H), 7.94 (d, J = 8.09 Hz , 2 H), 8.68 (d, J = 4.78 Hz, 1 H). Example 286 1 H NMR (300 MHz, CDCl 3), δ ppm 0.82 (s, 9 H), 0.99 (m, 9 H), 2.54 (m, 4 H), 2.61 (d, J = 9.19 Hz, 1 H), 2.77 (m, 1 H), 2.87 (m, 2 H), 3.07 (m, 1 H), 3.16 (m, 1 H), 3.33 (dd, J = 8, 82, 3.31 Hz, 1 H), 3.59 (d, J = 9.56 Hz, 1 H), 3.64 (s, 3 H), 3.79 (s, 3 H), 3.87 (c, J = 13.48 Hz, 2 H), 4.04 (s, 1 H), 4.09 (d, J = 8.09 Hz, 1 H), 4.50 (m, 2 H), 4.69 (s, 1 H), 5.29 (d, J = 9.93 Hz, 1 H), 6.28 (d, J = 9.56 Hz, 1 H), 6.38 (s, 1 H), 6, 84 (m, 2 H), 7.11 (m, 7 H), 7.20 (m, 2 H), 7.57 (t, J = 7.72 Hz, 1 H) Example 287 1 H NMR (300 MHz, CDCl 3), δ ppm 0.72 (m, 1 H), 0.83 (t, J = 6.99 Hz, 6 H), 1.02 (m, 18 H), 1.33 (m, 1 H), 1.65 (m, 2 H), 2.32 (s, 1 H), 2.51 (d, J = 2.94 Hz, 1 H), 2.55 (s, 3 H), 2.63 (s, 1 H), 2.71 (m, 3 H), 2.89 (m, 2 H), 3.07 (m, 1 H), 3.17 (m, 1 H), 3.36 (m, 1H), 3.61 (s, 1H), 3.63 (s, 3 H), 3.72 (d , J = 9.56 Hz, 1 H), 4.06 (d, J = 7.35 Hz, 2 H), 4.46 (d, J = 16.18 Hz, 2 H), 4.65 (s, 1H), 5.37 (d, J = 9.56 Hz, 1 H), 6.37 (s, 1 H), 6.50 (s, 1 H), 7.04 (s, 1H), 7.08 (m, 2 H), 7.17 (m, 3 H).

Example 288 1 H NMR (300 MHz, CDCl 3), δ ppm 0.82 (s, 9 H), 0.85 (s, 1 H), 0.96 (s, 9 H), 1.04 (m, 2 H), 2.35 (d, J = 3.31 Hz, 1 H), 2.38 (s, 3 H), 2.55 (dd, J = 12.13, 2.94 Hz, 2 H) , 2.75 (m, 1 H), 2.96 (m, 1 H), 3.35 (m, 1 H), 3.58 (m, 1 H), 3.64 (s, 3 H) , 3.79 (s, 3 H), 3.87 (m, 2 H), 4.02 (m, 1 H), 4.11 (d, J = 9.56 Hz, 1 H), 4, 30 (d, J = 15.08 Hz, 1 H), 4.50 (m, 1 H), 4.68 (s, 1 H), 5.29 (d, J = 8.46 Hz, 1 H ), 6.26 (d, J = 9.19 Hz, 1 H), 6.41 (s, 1 H), 6.85 (m, 2 H), 7.06

5 (m, 2 H), 7.14 (m, 3 H), 7.22 (d, J = 8.46 Hz, 2 H), 8.38 (s, 1 H), 8.43 (d , J = 4.78 Hz, 1H). Example 289 1 H NMR (300 MHz, CDCl 3), δ ppm 0.85 (t, J = 7.17 Hz, 6 H), 0.99 (m, 18 H), 1.25 (s, 1 H), 1.36 (m, 2 H), 1.66 (m, 1 H), 2.38 (s, 3 H), 2.55 (d, J = 2.94 Hz, 1H), 2.73 ( m, 2 H), 2.88 (t, J = 7.54 Hz, 3 H), 2.96 (m, 1 H), 3.33 (d, J = 3.68 Hz, 1 H), 3.58 (d, J = 10.30 Hz, 1 H), 3.65 (s, 3 H), 3.71 (d, J = 9.19 Hz, 1 H), 4.04 (s, 1H), 4.12 (m, 1 H), 4.32 (d, J = 14.71 Hz, 1 H), 4.49 (m, 1 H), 4.60 (s, 1 H), 5.37 (d, J = 7.72 Hz, 1 H), 6.33 (d, J = 9.19 Hz, 1 H), 6.49 (s,

10 1 H), 7.07 (m, 3 H), 7.15 (m, 3 H), 8.39 (s, 1 H), 8.44 (d, J = 4.78 Hz, 1 H ). Example 209 1H NMR (300 MHz, CDCl3) δ ppm 0.76 (t, J = 6.43 Hz, 3 H), 0.85 (m, 12 H), 0.99 (m, 1H), 1, 22 (t, J = 6.99 Hz, 2 H), 1.29 (m, 2 H), 1.89 (s, 1 H), 2.63 (d, J = 3.31 Hz, 1 H ), 2.84 (m, 4 H), 3.02 (m, 3 H), 3.02 (m, 2 H), 3.61 (d, J = 9.56 Hz, 2 H), 3 , 95 (m, 2 H), 4.09 (m, 2 H), 4.81 (m, 2 H), 5.22 (d, J = 8.09 Hz, 1 H), 6.50 ( d, J = 9.56 Hz, 2 H), 7.08 (m, 5 H), 7.22 (m, 2 H), 7.43 (d, J = 8.09 Hz, 2 H), 7.60 (t, J = 6.99 Hz, 1 H), 7.73 (m, 3 H), 7.95 (d, J = 8.46 Hz,

15 2 H), 8.14 (d, J = 7.72 Hz, 1 H), 8.20 (d, J = 8.09 Hz, 1 H), 8.68 (d, J = 4.41 Hz, 1 H), 8.88 (d, J = 4.41 Hz, 1 H).

Claims (20)

1. A compound, stereoisomer of the compound, ester of the compound, a pharmaceutically acceptable salt of the compound, a stereoisomer, or an ester, or a combination thereof in which: The compound corresponds in structure to formula (II): X is O; R1 is alkyl; R 2 is selected from the group consisting of cycloalkylalkyl, cycloalkenyl alkyl, arylalkyl, heterocycloalkyl and heteroarylalkyl; R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkylalkyl, cycloalkenylalkyl, heterocycloalkyl, heteroarylalkyl, arylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkylalkyl, alkyl-alkyl-alkyl, alkyl-alkyl-alkyl AlkylORO, -alkylSO2Ra, -alkylNRaRb, -alkylC (= O) ORa, -alkylN (Rb) C (= O) ORa, -alkylN (Rb) C (= O) Ra, alkylN (Rb) SO2Ra and -alkylN ( Rb) SO2NRaRb, in which: the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, cycloalkyl moiety of the cycloalkylalkyl moiety, cycloalkenyl of the cycloalkenyl alkyl moiety, heterocycle of the heterocycloalkyl moiety, heteroaryl of Heteroarylalkyl, and the aryl moiety of the arylalkyl are substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -SH, -S (alkyl), -S (haloalkyl), -SO2 (alkyl), -SO2 (haloalkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2, -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, -C (= O) O (alkyl), C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, Cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkylS (alkyl), -alkylSO2 (alkyl), -alkylNH2, alkylN (H) (alkyl), -alkN (alkyl) 2, -alkN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylC (= O) OH, -alkylC (= O) O (alkyl), -alkylC (= O) NH2, -alkylC (= O) N (H ) (alkyl), alkylC (= O) N (alkyl) 2, -C1 alkyl (= O) alkyl and R3a; R3a is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy and heterocyclooxy, in which each substituent is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, -SH, -S (alkyl), SO2 (alkyl), -NH2, -N (H) (alkyl), -N (alkyl) 2 , -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -C (= O) OH, 35 C (= O) O (alkyl), -C (= O) NH2, -C (= O) N (H) (alkyl), -C (O) N (alkyl) 2, -C (= O) alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH, -alkyl (alkyl), -alkylSO2 (alkyl), -alkylNH2, -alkyl N (H) (alkyl), -alkylN (alkyl) 2, -alkyl (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, -alkylC (= O) OH, alkylC (= O) O (alkyl), -alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl), -alkyl C (= O) N (alkyl) 2 and -alkyl C (= O) alkyl; 40 R4 is selected from the group consisting of: a) -C (O) CH (R8) NHC (O) R9, b) -C (O) R9, c) -C (O) CH2-O-aryl, substituted with 0, 1, 2 or 3 substituents independently selected from the group 45 consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2, d) -C (O) CH2-O-heteroaryl, substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, halo, cyano, nitro, formyl, oxo, hydroxyl, alkoxy, hydroxyalkyl, Alkoxyalkyl, haloalkyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, nitroalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2, and) F) 5 g) h) i) j) k) Y I) -SO2R14; R5 is selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle, in which: Each substituent is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, -ORa, -OC (= O) Ra, -SRa, - SORa, -SO2Ra, -SO2NRa, -SO2OR3, -NRaRb, -N (Rb) NRaRb, -N (Rb) C (= O) Ra, -N (Rb) SO2Ra, -N (Rb) C (= O) ORa, N (Rb) C (= O) NRaRb, -N (Rb) SO2NRaRb, -C (= O) Ra, -C (= O) NRaRb, -C (= O) ORa, azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylORa, -alkylOC (= O) Ra, -alkylSRa, -alkylSORa, -alkylSO2Ra, -alkylSO2NRa, alkylSO2ORa, -alkylRRRb, -C (H) = N (ORa), -C (alkyl) = N (ORa ), -C (H) = NNR3Rb, -C (alkyl) = NNRaRb, C (H) (= NORa) NRaRb, -C (alkyl) (= NORa) NRaRb, -alkyl N (Rb) NRaRb, -alkylN (Rb ) C (= O) Ra, alkyl N (Rb) C (= O) ORa, -alkylN (Rb) C (= O) NRaRb, -alkylN (Rb) SO2NR3Rb, -alkylN (Rb) SO2Ra, -alkylC (= O ) Ra, alkylC (= O) ORa, -alkylC (= O) NRaRb and R5a; R5a is selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, in which: each substituent is substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (H) ( alkyl), N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, -N (alkyl) C (= O) alkyl, -N (H) C (= O) NH2, N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C (= O) OH , -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, cyanoalkyl, formylalkyl, haloalkyl, hydroxyalkyl , alkoxyalkyl, -alkyl NH2, alkylN (H) (alkyl), -alkylN (alkyl) 2, -alkylN (H) C (= O) alkyl, -alkylN (alkyl) C (= O) alkyl, alkylN (H) C (= O) NH2; -alkyl N (H) C (= O) N (H) (alkyl), -alkyl N (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, alkylC (= O) Oalkyl, - alkylC (= O) NH2, -alkylC (= O) N (H) (alkyl) and -alkylC (= O) N (alkyl) 2; R8 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl and arylalkyl, in which: each of said substituents is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, cyano, formyl, nitro, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, -NH2, -N (R) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, C (= O) N (H) (alkyl ), -C (= O) N (alkyl) 2, -C (= O) alkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH2, alkylN (H) alkyl, -alkylN (alkyl) 2, -alkylC (= O) OH, -C1 alkyl (= O) Oalkyl, -C1 alkyl (= O) NH2, C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2 alkyl; R9 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heterocycle, heteroaryl and OR9a, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2; R9a is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl and heterocycloalkyl, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of hydroxy, alkoxy, halo, cyano, nitro, formyl, alkyl, alkenyl, alkynyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) alkyl, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, C (= O) N (H) (alkyl) and -C (= O) N (alkyl) 2; R10 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl and heteroarylalkyl, wherein: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, -SRa, -SORa, -SO2R3, - SO2NRaRb, -C (= O) Ra, -NRaRb, -N (Rb) C (= O) Ra, -N (Rb) C (= O) ORa, -N (Rb) SO2Ra, N (Rb) SO2NRaRb, -N (Rb) C (= NH) NRaRb, -N (Rb) C (= O) NRaRb, -C (= O) NRaRb and -C (= O) ORa; R11 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R12 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R13 is selected from the group consisting of alkyl and haloalkyl; R14 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl and heterocycle, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, formyl, alkyl, alkenyl, hydroxy, alkoxy, haloalkyl, -NH2, -N (H) alkyl, -N (alkyl) 2, -C (= O) OH, -C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl) and C (= O) N (alkyl) 2; Z is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Z 'is selected from the group consisting of -CH2-, -NH-, -O-and -S-; Ra and Rb in each case are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycle, arylalkyl and heteroarylalkyl, in which: each of said substituents is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, -NH2, -N ( H) (alkyl), -N (alkyl) 2, -SH, -S (alkyl), -SO2 (alkyl), -N (H) C (= O) alkyl, N (alkyl) C (= O) alkyl , -N (H) C (= O) NH2, -N (H) C (= O) N (H) (alkyl), -N (H) C (= O) N (alkyl) 2, -C ( = O) OH, C (= O) Oalkyl, -C (= O) NH2, -C (= O) N (H) (alkyl), -C (= O) N (alkyl) 2, -C (= O) alkyl, cyanoalkyl, formylalkyl, nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkyl NH2, -alkyl N (H) (alkyl), -alkylN (alkyl) 2, alkylN (H) C (= O) NH2, -alkylN (H ) C (= O) N (H) (alkyl), -alkylN (H) C (= O) N (alkyl) 2, -alkylC (= O) OH, -alkylC (= O) Oalkyl, -alkylC (= O) NH2, -C1 (= O) N (H) (alkyl), -C (= O) N (alkyl) 2 and -C (= O) alkyl; and n is 1. 2. The compound, stereoisomer, ester, salt or a combination of claim 1, wherein the compound is selected from the group consisting of: (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- methyl pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- (3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl) pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S, 2S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3- thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) 3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl; 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4 tert-butyl-phenylbutyl] 2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate; (1S, 2S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-benzimidazol-2- il) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate methyl ; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S, 2S) -1 - ({2- (4-bromobenzyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2- oxo-3- (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methyl butylcarbamate; (1S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3 -pyridinyl methyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropyl methyl carbamate; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl- Methyl 2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- Methyl (3-pyridinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutyl carbamate; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S) -3,3-dimethyl-2- (3 - {[2- (5-methyl-3-isoxazolyl) - 1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) butanoyl] amino} -2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) - Methyl 2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S) -3,3-dimethyl-2- (2-oxo-3 - {[2- (3-pyridinyl) - 1,3-thiazol-4-yl] methyl} -1imidazolidinyl) butanoyl] amino} -2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2- methyl dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3 - ((2-methyl- 1,3-thiazol-4-yl) 1,3-thiazol-4-ylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) - Methyl 2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - ({2 - ((2S, 3S) -3 - {[(2S, 3S) -2- (3 - {[2- (2-ethyl-4-pyridinyl) -1,3- thiazol-4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -2-hydroxy-4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2 , Methyl 2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (2-pyridinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(4-methyl-3-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - [(2S, 3S) -3 - ({(2S) -3,3-dimethyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] methyl butanoyl} amino) -2-hydroxy4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3 -pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2- methyl dimethylpropylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-pyridazinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (trifluoromethyl ) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -2- {3 - [(2-isopropyl-1,3-thiazol-4-yl) methyl] -2-oxo-1-imidazolidinyl} -3,3dimethylbutanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethyl-propylcarbamate methyl ; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2 - {[2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] 2 , Methyl 2-dimethylpropylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3- thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazole- 4-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2 - {[2- (2-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2, Methyl 2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole- Methyl 4-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazol-4- il) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1, 3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutyl-carbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1,3- thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2-methyl-1,3-thiazol-4- il) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1 imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2- [3-methyl-2- (2-oxo-1-pyrrolidinyl) butanoyl] -1- [ 4- (2-Pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} methyl pentanamide; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridazinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -2- {3 - [(6-acetyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl } -3,3-dimethylbutanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; 6 - [(3 - {(1S, 4S, 5S, 10S) -4-benzyl-1,10-diterc-butyl-5-hydroxy-2,9,12-trioxo-7- [4- (2-pyridinyl) ) benzyl] -13-oxa-3,7,8,11 tetraazatetradec-1-yl} -2-oxo-1-imidazolidinyl) methyl] -2-pyridinecarboxylate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - [(2S, 3S) -3-methyl-2- (2-oxo-1-imidazolidinyl)) pentanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- methyl pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) - 2-Pyridinyl] methyl} -2-oxo-1-imidazolidinyl) 3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2-Oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (8-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-4-quinolinyl) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(3-methyl-3H-imidazo) 4,5-b] pyridin-2-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-pyridazinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(5-methyl-2-thienyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S, 2S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6- methyl methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2-methylbutylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -3 - ({(2S, 3S) -2- [3 - ({2 - [(1S) -1- (acetylamino) ethyl] -1 , 3-thiazol-4-yl} methyl) -2-oxo-1-imidazolidinyl] -3methylpentanoyl} amino) -2-hydroxy-4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl ) -2,2-methyl dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {[(4S, 5R) -5-methyl-2-oxo-1,3-oxazolidin- 4-yl] carbonyl} -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1- imidazolidinyl} pentanamide; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) -2- pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) - 2-Pyridinyl] methyl} -2-oxo-1-imidazolidinyl) 3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} -2 -oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2-pyridinyl] methyl} Methyl -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2,2-dimethyl-5-oxotetrahydro-3-furanyl) carbonyl] -1- [4- (2-pyridinyl) ) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl] pentanamide; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -2- [3- (imidazo [1,5-a] pyridin-3-ylmethyl) ) Methyl -2-oxo-1-imidazolidinyl] -3-methylpentanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropyl-carbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - {[(2S) -5-oxopyrrolidinyl] carbonyl} -1- [4- (2-pyridinyl) benzyl ] hydrazino} propyl-3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanamide; 2 - {(2S, 3S) -2-hydroxy- 3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2 - (3S) -4,4-dimethyl-2-oxotetrahydro-3-furanyl [4- (2-pyridinyl) benzyl] hydrazinecarboxylate; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S , 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- [4- (2 -pyridinyl) benzyl] (3R) -4,4-dimethyl-2-oxotetrahydro-3-furanyl hydrazinecarboxylate; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) - 3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- [4- ( Methyl 2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2- ( (2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3thiazol-4-yl] methyl} -2-oxo-1- im idazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- ((methoxy methyl) -1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate of (3R) -2-oxotetrahydro-3-furanyl; 2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} pentanoyl) amino] 4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazinecarboxylate of (3S) -2-oxotetrahydro-3-furanyl; (1S) -1 - [(2- [4- (diethylamino) benzyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - methyl [[6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropyl-carbamate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S) -3,3-dimethyl-2- (2-oxo-1-imidazolidinyl) butanoyl] -1 - [4- (2-Pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanamide; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2 - (3 - {[6- (1-hydroxy-1-methylethyl) -2pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} - Methyl 2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy-1-methylethyl) 2-pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-methyl dimethylpropylcarbamate; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2 - (3 - {[6- (hydroxymethyl) -2pyridinyl] methyl} -2-oxo-1-imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) -2pyridinyl] methyl) -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(4,4-dimethyl-2-oxotetrahydro-3-furanyl) carbonyl] -1- [4- (2-pyridinyl) ) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanamide; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl propylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1 -hydroxy-1-methylethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- Methyl (1-hydroxy-1-methyl ethyl) -2-pyridinyl] methyl} -2oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) ) Methyl -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- ((hydroxymethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (1-hydroxy-1 -methylethyl) -2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (1-hydroxy -1-Methylethyl) -2-pyridinyl] methyl} -2oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[6- (hydroxymethyl) -2- methyl pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3,3-dimethylbutanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2- (cyclopropylmethyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[6- (hydroxymethyl) - Methyl 2-pyridinyl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate; (1S, 2S) -1 - [(2-benzyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2- methyl methyl-1,3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2-methylbutylcarbamate; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (3-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl propylcarbamate; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (2-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl propylcarbamate; (1S) -1 - [(2-benzyl-2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl propylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2 - {[2- (3-pyridinyl) -1,3-thiazol-4-yl] methyl} hydrazino) carbonyl] -2, Methyl 2-dimethylpropylcarbamate; (1S) -1 - {[2-benzyl-2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[ 2- (3-Pyridinyl) -1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -2- [3- (imidazo [1 , Methyl 5-a] pyridin-3-ylmethyl) -2-oxo-1imidazolidinyl] -3-methylpentanoyl} amino) -4-phenylbutyl] hydrazino] carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (imidazo [1.5 -a] pyridin-3-ylmethyl) -2-oxo-1imidazolidinyl] -3,3-dimethylbutanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (imidazo [1,5-a] pyridin-3-ylmethyl) - Methyl 2-oxo-1-imidazolidinyl] -3,3-dimethylbutanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2- methyl oxo-3- (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S, 2S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(2-methyl-1, Methyl 3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate; (1S, 2S) -1 - ({2-benzyl-2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- Methyl (4-quinolinylmethyl) -1imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methyl butylcarbamate; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2- Isopropyl-1,3-thiazol-4-yl) methyl] -2-oxo-1imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(6- methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2-isopropyl-1,3-thiazol-4- il) methyl] -2-oxo-1-imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(2-isopropyl-1,3-thiazol-4- il) methyl] -2-oxo-1-imidazolidinyl} -3methylpentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethyl-propylcarbamate methyl ; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-3-pyridinyl) ) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3-pyridinyl) -1 , 3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate methyl; (1S) - 1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3-pyridinyl) - 1,3-thiazol-4-yl] methyl} -1imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (3,3-dimethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -3-methyl-2- (2-oxo-3 - {[2- (3 -pyridinyl) -1,3-aunt zol-4il] methyl} -1-imidazolidinyl) pentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethyl-propylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(3-methylimidazo [1,5-a] pyridin- 1-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(3- methyl imidazo [1,5-a] pyridin-1-yl) methyl] -2-oxo1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (1H-indazol-3-ylmethyl) -2-oxo-1- methyl imidazolidinyl] -3,3dimethylbutanoyl} amino) -4-phenylbutyl] -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2- (3,3-dimethylbutyl) -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S) -2- [3- (1H-indazol-3 -methyl) -2-oxo-1-imidazolidinyl] -3,3dimethylbutanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -2- {3 - [(6-isopropyl-2-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} -3-methylpentanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1-methyl-1H-indazol-3-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(1- methyl-1H-indazol-3-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(2- methyl-1H-benzimidazol-5-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -3 - [((2S) -2- {3 - [(6-tert-butyl-2-pyridinyl) methyl] -2-oxo-1 -imidazolidinyl} -3,3-dimethylbutanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropyl-carbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylpropylcarbamate methyl; 4-hydroxy-2 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- 4-yl] methyl} -2-oxo-1-imidazolidinyl) 3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -1-pyrrolidinecarboxylate methyl; (1S, 2R) -2-hydroxy-1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) - 1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) propylcarbamate methyl; (1S) -1-cyclohexyl-2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1.3 -thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-oxoethylcarbamate methyl; (1S) -1-benzyl-2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1.3 -thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-oxoethylcarbamate methyl; (1S) -1- (cyclohexylmethyl) -2- {2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methyl methoxy) - 1,3-thiazol-4-yl] methyl} -2-oxo-1imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2- [4- (2-pyridinyl) benzyl] hydrazino} -2-oxoethylcarbamate of methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S) -3-methyl-2- {3 - [(2-methyl-1,3-thiazole- Methyl 4-yl) methyl] -2-oxo-1imidazolidinyl} butanoyl) amino] -4-phenylbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Tert-Butyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Methyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] (3S) -tetrahydro-3-furanyl hydrazinecarboxylate; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S) -3,3-dimethyl-2- (2-oxo-1-imidazolidinyl) butanoyl] -1 - [4- (2-Pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2,6-dimethylphenoxy) acetyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} - 2-hydroxypropyl) -3methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- (2 - [(2-methylphenoxy) acetyl] -1- [4- (2-pyridinyl) benzyl] hydrazino ) propyl) -3-methyl2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2- (3-hydroxy-2-methylbenzoyl) -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-2-hydroxy-3- {2 - [(2S, 3S) -3-methyl-2- (2-oxo-1-imidazolidinyl)) pentanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} propyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (2S, 3S) -N - ((1S, 2S) -1-benzyl-3- {2 - [(2S, 3S) -2- (2,4-dioxo-1-imidazolidinyl) -3-methylpentanoyl] - 1- [4- (2-Pyridinyl) benzyl] hydrazino} -2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; 2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] benzyl hydrazinecarboxylate; (1S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) - Ethyl 1-imidazolidinyl] pentanoyl} amino) 4-phenylbutyl] -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate; (2S, 3S) -N - ((1S, 2S) -3- {2 - [(2S) -2- (acetylamino) -3,3-dimethylbutanoyl] -1- [4- (2-pyridinyl) benzyl] hydrazino} -1-benzyl-2-hydroxypropyl) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) -1-imidazolidinyl] pentanamide; (1S, 2S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) ) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (3-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2- [4- (1,3-benzodioxol-5-yl) benzyl] -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S ) -3-methyl-2- [2-oxo-3- (4quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2- [4- (3,5-dimethyl-4-isoxazolyl) benzyl] -2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S ) -3-methyl-2- [2-oxo-3- (4quinolinylmethyl) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S, 2S) -1 - ({2 - [(2S, 3S) -2-hydroxy-3 - ({(2S, 3S) -3-methyl-2- [2-oxo-3- (4-quinolinylmethyl) ) -1-imidazolidinyl] pentanoyl} amino) -4-phenylbutyl] -2- [4- (4-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl propylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2- methyl pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (cyclohexy (methyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- { (2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) methyl amino] -4-phenylbutyl} -2-isobutylhydrazino) carbonyl] -2,2-dimethyl propylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [(( 2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (2-phenylethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (2-thienylmethyl) hydrazino] carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (2-naphthylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-isopropylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-isopropoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,4-dimethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (3-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (2-ethylbutyl) -2 - ((2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- ( 4-ethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] - Methyl 2-oxo-1imidazolidinyl) pentanoyl) amino] -4-phenylbutyl) hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (3-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (trifluoromethyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-hydroxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (4-fluorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [3- (4-methylphenoxy) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- [3- (4-chlorophenoxy) benzyl] -2 - ((2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl) hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (2-quinolinylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(5-ethyl-2-thienyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl- Methyl 2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (2-octinyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; 6- (1 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2- methyl oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3-dimethylbutanoyl} hydrazino) hexanoate; (1S) -1 - [(2 - [(5-ethyl-2-furyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl- Methyl 2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropyl-carbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (1H-imidazol-1-yl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- [4- (acetylamino) benzyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - methyl [[6-methyl-2-pyridinyl) methyl] -2-oxo1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropyl-carbamate; 4 - [(1 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2 - {(2S) -2 - [(methoxycarbonyl) amino] -3,3dimethylbutanoyl} hydrazino) methyl] methyl benzoate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (3-phenoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [3- (4-methoxyphenoxy) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-tert-butylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (2,3-dihydro-1,4-benzodioxin-6-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- (3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl) pentanoyl) amino] -4-phenyl butyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- {4 - [(trifluoromethyl) sulfanyl] benzyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (3,7-dimethyl-6-octenyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2 - {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropyl-carbamate methyl; (1S) -1 - [(2- (cyclopropylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6- methyl methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(2-ethyl-1H-imidazol-5-yl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) - 3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] 2-oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenyl butyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (2,3-dihydro-1-benzofuran-5-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3 methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-chlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,4-dimethoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [[(6-Methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropyl-carbamate methyl; (1S) -1 - [(2- (3-fluoro-4-methoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- { 3 - [(6-methyl-2-pyridinyl) methyl] -2oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - [(2- (1,3-benzodioxol-5-ylmethyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2 - {3 - [(6-methyl-2-pyridinyl) methyl] -2oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxy-3-methylbenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (4-hydroxy-3-methoxybenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- { 3 - [(6-methyl-2-pyridinyl) methyl] -2oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- [4- (methylsulfonyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (1H-imidazol-2-ylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (5-hydroxypentyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - [(4,5-dimethyl-2-furyl) methyl] -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3- methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2oxo-1-imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethyl-propylcarbamate methyl; (1S) -1 - [(2- (3-chlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,5-dimethylbenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl)) methyl methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2-neopentylhydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (1,3-dimethylbutyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2- (4-cyanobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [( Methyl 6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2-cyclohexyl-2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl- Methyl 2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2- (3,4-dichlorobenzyl) -2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate methyl; (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (4-pyridinyl) -1,3-thiazol-4-yl] methyl} methyl hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2- [3- (5-pyrimidinyl) benzyl] hydrazino} carbonyl) -2,2-dimethylpropylcarbamate methyl ; (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (5-methyl-3-isoxazolyl) -1,3-thiazol-4- methyl il] methyl} hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - {[2- (2-pyridinyl) -1,3-thiazol-4-yl] methyl} methyl hydrazino) carbonyl] -2,2-dimethylpropylcarbamate; (1S) -1 - ({2 - ((2S, 3S) -2-hydroxy-3 - {[(2S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazol-4- il] methyl} -2-oxo-1-imidazolidinyl) -3,3dimethylbutanoyl] amino} -4-phenylbutyl) -2 - [(2-isopropyl-1,3-thiazol-4-yl) methyl] hydrazino} carbonyl) -2,2-methyl dimethylpropylcarbamate; (1S) -1 - {[2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methoxymethyl) -1,3-thiazole- Methyl 4-yl] methyl} -2-oxo-1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) -2-isopentylhydrazino] carbonyl} -2,2-dimethylpropyl-carbamate; (1S) -1 - {[2- (3,4-dimethoxybenzyl) -2 - ((2S, 3S-2-hydroxy-3 - {[(2S, 3S-2- (3 - {[2- (methoxy methyl) -1,3-thiazol-4-yl] methyl} -2-oxo1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) -1 - {[2- (3,4-dimethylbenzyl) -2 - ((2S, 3S) -2-hydroxy-3 - {[(2S, 3S) -2- (3 - {[2- (methyl methoxy ) -1,3-thiazol-4-yl] methyl} -2-oxo1-imidazolidinyl) -3-methylpentanoyl] amino} -4-phenylbutyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl; (1S) - 1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2 -oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2-methylbutylcarbamate methyl; (1S, 2S) -1 - [(2 - {(2S, 3S ) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4 -phenylbutyl} -2-isopentylhydrazino) carbonyl] -2-methylbutylcarbamate methyl; (1S, 2S) -1 - ({2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) - 3-methyl-2- {3 - [(6-methyl-2-pyridinyl) methyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-fen methyl ilbutyl} -2- [4- (2-pyridinyl) benzyl] hydrazino} carbonyl) -2-methylbutylcarbamate; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] Methyl -2-oxo-1-imidazolidinyl} butanoyl) amino] -2hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3- [2- (6-methyl-2-pyridinyl) ethyl] -2-oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethyl propylcarbamate methyl; (1S) -1 - {[2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2- (4-methoxybenzyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate; (1S) -1 - [(2 - {(2S, 3S) -3 - [((2S) -3,3-dimethyl-2- {3 - [(4-methyl-3-pyridinyl) methyl] -2 -oxo-1-imidazolidinyl} butanoyl) amino] -2-hydroxy-4-phenylbutyl} -2-isopentylhydrazino) carbonyl] -2,2-dimethyl propylcarbamate methyl; and (1S) -1 - {[2 - {(2S, 3S) -2-hydroxy-3 - [((2S, 3S) -3-methyl-2- {3- [2- (6-methyl-2) -pyridinyl) ethyl] -2-oxo-1imidazolidinyl} pentanoyl) amino] -4-phenylbutyl} -2- (4-pyridinylmethyl) hydrazino] carbonyl} -2,2-dimethylpropylcarbamate methyl.

3.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R4 is -C (O) C (H) (R8) NHC (O) R9.

Four.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R4 is -C (O) C (H) (R8) NHC (O) R9 and R9 is -OR9a.

5.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl and R9 is -OR9a.

6.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxy-alkyl, arylalkyl, heteroarylalkyl and heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl and R9 is -OR9a.

7.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl and heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a, and R2 is arylalkyl.

8.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl and heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a, R9a is alkyl, and R2 is arylalkyl.

9.

The compound, stereoisomer, ester, salt or a combination of claim 1, wherein:

R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl and heterocycloalkyl, R4 is -C (O) C (H) (R8) NHC (O) R9, R8 is alkyl, R9 is -OR9a, R9a is alkyl, R2 is arylalkyl and R5 is heteroaryl.

10.

A pharmaceutical composition comprising:

a therapeutically effective amount of one or more compounds, stereoisomers, esters and / or salts of claim 1, and a pharmaceutically acceptable carrier.

eleven.

 A pharmaceutical composition comprising:

a therapeutically effective amount of one or more compounds, stereoisomers, esters and / or salts of claim 1, and one, two, three, four, five or six agents selected from the group consisting of a second HIV protease inhibitor, a HIV reverse transcriptase inhibitor, an HIV entry / fusion inhibitor, an HIV integrase inhibitor and an HIV budding / maturation inhibitor and a pharmaceutically acceptable carrier.

12.

 The pharmaceutical composition of claim 11, wherein the second HIV protease inhibitor is selected from the group consisting of ritonavir, lopinavir, saquinavir, amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126, TMC-114 , mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI272, DPC-681, DPC-684 and GW640385X.

13.

 The pharmaceutical composition of claim 11, wherein the HIV reverse transcriptase inhibitor is selected from the group consisting of lamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210 , Racivir (± -FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirin, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV -150, TMC-120 and TMC-125.

14.

 The pharmaceutical composition of claim 11, wherein the HIV entry / fusion inhibitor is selected from the group consisting of enfuvirtide (T-20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100, BMS806, FP21399, GW873140, Schering C (SCH-C), Schering D (SCH-D), TNX-355 and UK-427857.

fifteen.

 The pharmaceutical composition of claim 11, wherein the HIV integrase inhibitor is selected from the group consisting of S-1360, zintevir (AR-177), L-870812 and L-870810.

16.

 The pharmaceutical composition of claim 11, wherein the HIV budding / modulation inhibitor is PA-457.

17.

 Use of one or more compounds, stereoisomers, esters and / or salts of claim 1 to prepare a medicament for inhibiting the replication of an HIV virus comprising contacting the virus with a therapeutically effective amount of the one or more compounds, stereoisomers, esters and / or salts.

18.

 Use of one or more compounds, stereoisomers, esters and / or salts of claim 1 to prepare a medicament for treating or preventing an HIV infection comprising administering to a patient in need of said treatment a therapeutically effective amount of the one or more compounds, stereoisomers, esters and / or salts.

19.

 Use of a pharmaceutical composition of any one of claims 10, 11, 12, 13, 14, 15 and 16 to prepare a medicament for treating or preventing an HIV infection comprising administering to a patient in need of said treatment or preventing the composition. Pharmaceutical

twenty.

Use of one or more compounds, stereoisomers, esters and / or salts of claim 1 to prepare a medicament for inhibiting an HIV protease comprising contacting the HIV protease with a therapeutically effective amount of the one or more compounds, stereoisomers, esters and / or salts.