WO2017157882A1 - Inhibiteurs de la voie de biosynthèse de la sérine - Google Patents

Inhibiteurs de la voie de biosynthèse de la sérine Download PDF

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WO2017157882A1
WO2017157882A1 PCT/EP2017/055898 EP2017055898W WO2017157882A1 WO 2017157882 A1 WO2017157882 A1 WO 2017157882A1 EP 2017055898 W EP2017055898 W EP 2017055898W WO 2017157882 A1 WO2017157882 A1 WO 2017157882A1
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aryl
alkyl
heterocyclyl
group
cycloalkyi
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Séverine RAVEZ
Cyril CORBET
Quentin SPILLIER
Olivier Feron
Raphaël FRÉDÉRICK
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Universite Catholique de Louvain UCL
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Universite Catholique de Louvain UCL
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to serine biosynthetic pathway inhibitors such as phosphoglycerate dehydrogenase inhibitors and phosphoserine aminotransferase 1 inhibitors, and to theses inhibitors for use as a medicament, more in particular for the prevention or treatment of cellular proliferative disorders.
  • This enzyme catalyzes the first step in the serine biosynthetic pathway ⁇ Scheme 1) with PHGDH (3-phosphoglycerate dehydrogenase), PSAT1 (phosphoserine aminotransferase 1 ) and PSPH (phosphoserine phosphatase) catalyzing the conversion of 3-phosphoglycerate into serine, together with the generation of NADH (reduced nicotinamide adenine dinucleotide) and aKG (a-ketoglutarate), the latter able to fuel the TCA (tricarboxylic acid) cycle.
  • PHGDH 3-phosphoglycerate dehydrogenase
  • PSAT1 phosphoserine aminotransferase 1
  • PSPH phosphoserine phosphatase
  • This pathway diverts a relatively small fraction of 3-phosphoglycerate from glycolysis to generate serine as well as equimolar amounts of NADH and a-ketoglutarate (aKG).
  • the serine pathway was identified as a vital source of aKG to fuel the TCA cycle in a variety of tumor cells. Serine supplement could not rescue tumor cells in which PHGDH and PSAT1 genes were knocked down, thereby identifying the serine pathway as a process providing malignant cells with critical amounts of its intermediary synthetic products, aKG and possibly NADH, instead of the end product, serine (that may also be taken up from the extracellular fluid).
  • a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof as defined in claim 1 is provided
  • a 1 is selected from the group consisting of S; and O;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyi; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -CO2R 20 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • R 5 is selected from the group consisting of hydrogen, alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl;
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ;
  • the present invention relates to a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof, wherein,
  • a 1 is selected from the group consisting of S; and O;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyl; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • m is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyl; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyl; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; - C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyi; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; - C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyi; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; - C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyi; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyi; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -
  • the present invention provides a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and a therapeutically effective amount of a compound according to the first aspect of the invention.
  • the present invention provides a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof, for use as a medicament, wherein,
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyl; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyl; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • m is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 15 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 6 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • the present invention relates to a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof, for use as a medicament, wherein,
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyi; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 2 °; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • the present invention provides a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof, for use in the prevention or treatment of a cellular proliferative disease, wherein,
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which the are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • m is an integer selected from 0, 1 , 2, or 3;
  • q is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R is independently selected from the group consisting of hydrogen; halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 8 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; - C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl;
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; - S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; - S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; - S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ;
  • the present invention relates to a compound of formula (I), a stereoisomer thereof, an enantiomer thereof, a racemic thereof, or a tautomer thereof, for use in the prevention or treatment of a cellular proliferative disease, wherein,
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyl; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyl; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiet selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • q is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyi; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyi; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2
  • each R 14 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 8 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; - C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl;
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 2 °; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • the present invention also provides a pharmaceutical composition according to the second aspect of the invention for use in the prevention or treatment of a cellular proliferative disease.
  • the present invention also provides a method of treatment of a cellular proliferative disease, comprising administering to a subject in need thereof an effective amount of a compound according to the first aspect of the invention, or a pharmaceutical composition according to the second aspect of the invention.
  • the present invention also provides a method for inhibiting serine biosynthesis comprising the step of contacting at least one enzyme of the serine biosynthetic pathway with an effective amount of a compound according to the first aspect of the invention, or as defined in the fourth aspect of the invention.
  • said at least one enzyme of the serine biosynthetic pathway is selected from the group comprising phosphoglycerate dehydrogenase and phosphoserine aminotransferase 1.
  • the present invention also provides a method for inhibiting phosphoglycerate dehydrogenase comprising contacting said phosphoglycerate dehydrogenase with an effective amount of a compound according to the first aspect of the invention, or as defined in the fourth aspect of the invention.
  • the present invention also encompasses the combined use of a compound according to the first aspect of the invention, or as defined in the fourth aspect of the invention, together with an immune checkpoint inhibitor.
  • Immune checkpoint inhibitors are described in e.g. WO201701 1666, IMS health Institute global Oncology report June 2016, Nature Reviews Clinical Oncology 2013 (13) 143-158, and Clin. Cancer research 2013 (19) 1021-1034.
  • Immune check point targets as provided in the aforementioned literature comprise : PD1 , PD-L1 , CTLA4, IDO, TDO, CD122, CD27, GITR, CD40, OX40, CD73, CD137, 4-1 BB, CSF1 R, LAG 3, KIR, TIM-3, IL2, ADA, STING and TIGIT.
  • the person skilled in the art will understand the advantage of combining the compounds of present invention with an immune check point inhibitor.
  • the compounds of the present invention may also be given in combination with CAR-T cell therapeutic strategy.
  • Combination of the compounds comprises either the administration of the compound of the present invention prior to immune checkpoint therapy, administration concomittant with immune checkpoint therapy, or administration after immune checkpoint therapy.
  • the person skilled in the art will know how to combine the respective compounds.
  • the cellular proliferative disorder may be cancer (e.g., breast cancer, prostate cancer, squamous cell cancer, small-cell lung cancer, non-small-cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, vulval cancer, thyroid cancer, hepatic carcinoma, gastric cancer, melanoma, or neck cancer).
  • cancer e.g., breast cancer, prostate cancer, squamous cell cancer, small-cell lung cancer, non-small-cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer
  • Figure 1 represents in Section (A) a graph plotting fluorescence intensity, as a function of time at different PHGDH concentrations.
  • Section (B) is a graph plotting fluorescence intensity, as a function of time at different PHGDH concentrations.
  • Section (C) is a graph plotting fluorescence intensity, as a function of time at different PHGDH concentrations.
  • Section (D) is a graph plotting fluorescence intensity, as a function of time at different PHGDH concentrations.
  • Figure 2 represents a graph plotting the cell density as a function of compound 40 concentration for BT20 and MDA-MB-231 cell lines.
  • Figure 3 represents a graph plotting the cell density as a function of compound 40 concentration for in presence of absence of serine.
  • Figure 4 represents in Sections (A) and (C) a representative immunobolot for PHGDH.
  • Section (B) is a graph plotting cell density (for 5 days) of SiHa and MDA-MB-231 cells in either serine-replete (+Ser) or serine-deplete (-Ser) medium. Data are shown as mean ⁇ SEM (n>3).
  • Section (D) is a graph plotting cell density (for 5 days) of shScr and shPHGDH cells in either serine-replete (+Ser) or serine-deplete (-Ser) medium. Data are shown as mean ⁇ SEM (n>3).
  • a compound means one compound or more than one compound.
  • the term "and/or,” when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a list is described as comprising group A, B, and/or C, the list can comprise A alone; B alone; C alone; A and B in combination; A and C in combination, B and C in combination; or A, B, and C in combination.
  • substituted is meant to indicate that one or more hydrogen atoms on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group, provided that the indicated atom's normal valence is not exceeded, and that the substitution results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation from a reaction mixture.
  • groups can be substituted, such groups may be substituted with one or more, and preferably one, two or three substituents.
  • Preferred substituents may be selected from but not limited to, for example, the group comprising halo, hydroxyl, alkyl, alkoxy, haloalkyl, haloalkyloxy, cycloalkyl, aryl, arylalkyl, heterocyclyl, heteroaryl, alkylthio, cyano, amino, nitro, carboxyl, aminocarbonyl, hydroxycarbonylalkyl, alkyloxycarbonyl, mono- or dialkylamino, mono- or dialkylaminocarbonyl, alkylcarbonyl, -S(0)alkyl, -S(0)2alkyl, alkylcarbonylamino, and mono or di-alkylaminocarbonylalkyl.
  • halo or "halogen” as a group or part of a group is generic for fluoro, chloro, bromo, iodo.
  • amino refers to the group -NH 2 .
  • hydroxyl or "hydroxy” as used herein refers to the group -OH.
  • thiol or "sulfuhydryl” refers to the group -SH.
  • nitro refers to the group -NO2.
  • cyano refers to the group -CN.
  • carboxy or “carboxyl” or “hydroxycarbonyl” as used herein refers to the group -CO2H.
  • aminocarbonyl refers to the group -CO-NH 2 .
  • alkyl refers to a hydrocarbyl group of formula C n H 2 n + i wherein n is a number greater than or equal to 1.
  • Alkyl groups may be linear or branched and may be substituted as indicated herein.
  • alkyl groups of this invention comprise from 1 to 6 carbon atoms, preferably from 1 to 5 carbon atoms, preferably from 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms, still more preferably 1 to 2 carbon atoms.
  • the subscript refers to the number of carbon atoms that the named group may contain.
  • Ci- 6 alkyl refers to a hydrocarbyl group of formula -C n H 2 n + i wherein n is a number ranging from 1 to 6.
  • “Ci- 6 alkyl” includes all linear or branched alkyl groups with between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t- butyl); pentyl and its isomers, hexyl and its isomers.
  • Ci -5 alkyl includes all includes all linear or branched alkyl groups with between 1 and 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers.
  • Ci- 3 alkyl includes all linear or branched alkyl groups with between 1 and 3 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl.
  • a "substituted alkyl” refers to an alkyl group substituted with one or more substituent(s) (for example 1 to 3 substituent(s), for example 1 , 2, or 3 substituent(s)) at any available point of attachment.
  • alkylene when used in conjunction with an alkyl group, i.e. "alkylene”, this is intended to mean the alkyl group as defined herein having two single bonds as points of attachment to other groups.
  • alkylene by itself or as part of another substituent, refers to alkyl groups that are divalent, i.e., with two single bonds for attachment to two other groups. Alkylene groups may be linear or branched and may be substituted as indicated herein.
  • Non-limiting examples of alkylene groups include methylene (-CH 2 -), ethylene (-CH2-CH2-), methylmethylene (- CH(CH 3 )-), 1-methyl-ethylene (-CH(CH 3 )-CH 2 -), n-propylene (-CH 2 -CH 2 -CH 2 -), 2-methylpropylene (- CH 2 -CH(CH 3 )-CH 2 -), 3-methylpropylene (-CH 2 -CH 2 -CH(CH 3 )-), n-butylene (-CH 2 -CH 2 -CH 2 -CH 2 -), 2- methylbutylene (-CH 2 -CH(CH 3 )-CH 2 -CH 2 -), 4-methylbutylene (-CH 2 -CH 2 -CH 2 -CH(CH 3 )-), pentylene and its chain isomers, hexylene and its chain isomers.
  • alkyl When the term “alkyl” is used as a suffix following another term, as in “hydroxyalkyl,” this is intended to refer to an alkyl group, as defined above, being substituted with one or two (preferably one) substituent(s) selected from the other, specifically-named group, also as defined herein.
  • hydroxyalkyl therefore refers to a -R a -OH group wherein R a is alkylene as defined herein.
  • haloalkyl refers to an alkyl group having the meaning as defined above wherein one, two, or three hydrogen atoms are each replaced with a halogen as defined herein.
  • Non-limiting examples of such haloalkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1 , 1 ,1-trifluoroethyl, trichloromethyl, tribromomethyl, and the like.
  • trihalomethyl refers to a Ci alkyl group (methyl) having the meaning as defined above wherein three hydrogen atoms are each replaced with a halogen as defined herein.
  • Non-limiting examples of such trihalomethyl groups include trichloromethyl, tribromomethyl, and the like.
  • alkoxy or "alkyloxy”, as a group or part of a group, refers to a group having the formula - OR b wherein R b is as defined herein above.
  • suitable alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy.
  • haloalkoxy refers to a group of formula -0-R c wherein R c is haloCi- 6 alkyl as defined herein.
  • suitable haloCi- 6 alkoxy include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 , 1 ,2,2-tetrafluoroethoxy, 2- fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy, 2,2,2-trichloroethoxy, trichloromethoxy, 2- bromoethoxy, pentafluoroethyl, 3,3,3-trichloropropoxy, 4,4,4-trichlorobutoxy.
  • alkenyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched, comprising one or more carbon-carbon double bonds.
  • the subscript refers to the number of carbon atoms that the named group may contain.
  • alkenyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched comprising one or more carbon-carbon double bonds and comprising from 2 to 6 carbon atoms.
  • C 2 - 4 alkenyl includes all linear, or branched alkenyl groups having 2 to 4 carbon atoms.
  • C 2 - 6 alkenyl groups are ethenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl, and the like.
  • alkenyl groups as defined herein are divalent groups having single bonds for attachment to two other groups, they are termed "alkenylene".
  • alkenylene by itself or as part of another substituent, refers to alkenyl groups that are divalent, i.e., with two single bonds for attachment to two other groups.
  • alkenyloxy refers to a group having the formula -OR d wherein R d is alkenyl as defined herein above.
  • alkynyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched, comprising one or more carbon-carbon triple bonds.
  • the subscript refers to the number of carbon atoms that the named group may contain.
  • C2- 6 alkynyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched comprising one or more carbon-carbon triple bonds and comprising from 2 to 6 carbon atoms.
  • C2-4alkynyl includes all linear, or branched alkynyl groups having 2 to 4 carbon atoms.
  • Non limiting examples of C2- 6 alkynyl groups include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and its chain isomers, 2-hexynyl and its chain isomers, and the like.
  • alkynyl groups as defined herein are divalent groups having single bonds for attachment to two other groups, they are termed “alkynylene”.
  • alkynylene by itself or as part of another substituent, refers to alkynyl groups that are divalent, i.e., with two single bonds for attachment to two other groups.
  • alkynyloxy refers to a group having the formula -OR e wherein R e is alkynyl as defined herein above.
  • cycloalkyl refers to a cyclic alkyl group, that is a monovalent, saturated, hydrocarbyl group having 1 or more cyclic structure, and comprising from 3 to 12 carbon atoms, more preferably from 3 to 10 carbon atoms, more preferably from 3 to 8 carbon atoms; more preferably from 3 to 6 carbon atoms.
  • Cycloalkyl includes all saturated hydrocarbon groups containing 1 or more rings, including monocyclic, bicyclic groups or tricyclic. The further rings of multi-ring cycloalkyls may be either fused, bridged and/or joined through one or more spiro atoms.
  • the subscript refers to the number of carbon atoms that the named group may contain.
  • the term “C3- 6 cycloalkyl” a cyclic alkyl group comprising from 3 to 6 carbon atoms.
  • Cs-scycloalkyl groups include but are not limited to adamantly, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicycle[2.2.1]heptan-2yl, (1 S,4R)-norbornan-2-yl, (1 R,4R)-norbornan-2-yl, (1 S,4S)-norbornan-2-yl, (1 R,4S)-norbornan-2-yl.
  • cycloalkylene When the suffix "ene” is used in conjunction with a cycloalkyl group, i.e. cycloalkylene, this is intended to mean the cycloalkyl group as defined herein having two single bonds as points of attachment to other groups.
  • cycloalkylene include 1 ,2-cyclopropylene, 1 , 1 -cyclopropylene, 1 , 1 -cyclobutylene, 1 ,2-cyclobutylene, 1 ,3-cyclopentylene, 1 , 1 -cyclopentylene, and 1 ,4-cyclohexylene.
  • a Csalkylene group may be for example * - CH2CH2CH2-*, * -CH(-CH 2 CH 3 )- * or * -CH CH(-CH 3 )- * .
  • a C 3 cycloalkylene group may be
  • aryl refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthyl), or linked covalently, typically containing 6 to 12 atoms; preferably 6 to 10, wherein at least one ring is aromatic.
  • the aromatic ring may optionally include one to two additional rings (either cycloalkyl, heterocyclyl or heteroaryl) fused thereto.
  • suitable aryl include C 6- i2aryl, preferably C 6- - l oaryl, more preferably C6-saryl.
  • Non-limiting examples of aryl comprise phenyl, biphenylyl, biphenylenyl, or 1-or 2-naphthanelyl; 1-, 2-, 3-, 4-, 5- or 6-tetralinyl (also known as "1 ,2,3,4- tetrahydronaphtalene); 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-azulenyl, 4-, 5-, 6 or 7-indenyl; 4- or 5-indanyl; 5-, 6-, 7- or 8-tetrahydronaphthyl; 1 ,2,3,4-tetrahydronaphthyl; and 1 ,4-dihydronaphthyl; 1-, 2-, 3-, 4- or 5-pyrenyl.
  • a "substituted aryl” refers to an aryl group having one or more substituent(s) (for example 1 , 2 or 3 substituent(s), or 1 to 2 substituent(s)), at
  • spiro atom refers to the atom that connects two cyclic structures in a spiro compound.
  • Non limiting examples of spiro atoms include quaternary carbon atoms.
  • spiro compound refers to a bicyclic compound wherein the two rings are connected through one atom.
  • arylene When the suffix "ene” is used in conjunction with an aryl group; i.e. arylene, this is intended to mean the aryl group as defined herein having two single bonds as points of attachment to other groups.
  • Suitable "arylene” groups include 1 ,4-phenylene, 1 ,2-phenylene, 1 ,3-phenylene, biphenylylene, naphthylene, indenylene, 1-, 2-, 5- or 6-tetralinylene, and the like. Where a carbon atom in an aryl group is replaced with a heteroatom, the resultant ring is referred to herein as a heteroaryl ring.
  • aryloxy refers to a group having the formula -OR 9 wherein R 9 is aryl as defined herein above.
  • arylalkyl as a group or part of a group, means a alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one aryl as defined herein.
  • arylalkyl group include benzyl, phenethyl, dibenzylmethyl, methylphenylmethyl, 3-(2-naphthyl)-butyl, and the like.
  • arylalkyloxy refers to a group having the formula -0-R a -R 9 wherein R 9 is aryl, and R a is alkylene as defined herein above.
  • heterocyclyl or “heterocycloakyl” or “heterocyclo”, as a group or part of a group, refer to non-aromatic, fully saturated or partially unsaturated cyclic groups (for example, 3 to 7 member monocyclic, 7 to 1 1 member bicyclic, or comprising a total of 3 to 10 ring atoms) which have at least one heteroatom in at least one carbon atom-containing ring; wherein said ring may be fused to an aryl, cycloalkyi, heteroaryl or heterocyclyl ring.
  • the heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows.
  • the rings of multi-ring heterocycles may be fused, bridged and/or joined through one or more spiro atoms.
  • Non limiting exemplary heterocyclic groups include aziridinyl, oxiranyl, thiiranyl, piperidinyl, azetidinyl, oxetanyl, pyrrolidinyl, thietanyl, 2-imidazolinyl, pyrazolidinyl imidazolidinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, succinimidyl, 3H-indolyl, indolinyl, chromanyl (also known as 3,4-dihydrobenzo[b]pyranyl), isoindolinyl, 2H-pyrrolyl, 1- pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, 4H-quinolizinyl, 2-oxopiperazinyl, piperazinyl, homopiperazin
  • aziridinyl as used herein includes aziridin-1-yl and aziridin-2-yl.
  • oxyranyl as used herein includes oxyranyl-2-yl.
  • thiiranyl as used herein includes thiiran-2-yl.
  • azetidinyl as used herein includes azetidin-1-yl, azetidin-2-yl and azetidin-3-yl.
  • oxetanyl as used herein includes oxetan-2-yl and oxetan-3-yl.
  • thietanyl as used herein includes thietan-2-yl and thietan-3- yl.
  • pyrrolidinyl as used herein includes pyrrolidin-1-yl, pyrrolidin-2-yl and pyrrolidin-3-yl.
  • tetrahydrofuranyl as used herein includes tetrahydrofuran-2-yl and tetrahydrofuran-3-yl.
  • tetrahydrothiophenyl as used herein includes tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl.
  • succinimidyl as used herein includes succinimid-1-yl and succininmid-3-yl.
  • dihydropyrrolyl as used herein includes 2,3-dihydropyrrol-1-yl, 2,3- dihydro-1 H-pyrrol-2-yl, 2,3-dihydro-1 H-pyrrol-3-yl, 2,5-dihydropyrrol-1-yl, 2,5-dihydro-1 H-pyrrol-3-yl and 2,5-dihydropyrrol-5-yl.
  • 2H-pyrrolyl as used herein includes 2H-pyrrol-2-yl, 2H-pyrrol- 3-yl, 2H-pyrrol-4-yl and 2H-pyrrol-5-yl.
  • 3H-pyrrolyl as used herein includes 3H-pyrrol-2-yl, 3H-pyrrol-3-yl, 3H-pyrrol-4-yl and 3H-pyrrol-5-yl.
  • dihydrofuranyl as used herein includes 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 2,5- dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 2,5-dihydrofuran-4-yl and 2,5-dihydrofuran-5-yl.
  • dihydrothiophenyl as used herein includes 2,3-dihydrothiophen-2-yl, 2,3-dihydrothiophen-3-yl, 2,3- dihydrothiophen-4-yl, 2,3-dihydrothiophen-5-yl, 2,5-dihydrothiophen-2-yl, 2,5-dihydrothiophen-3-yl, 2,5-dihydrothiophen-4-yl and 2,5-dihydrothiophen-5-yl.
  • imidazolidinyl as used herein includes imidazolidin-1-yl, imidazolidin-2-yl and imidazolidin-4-yl.
  • pyrazolidinyl as used herein includes pyrazolidin-1-yl, pyrazolidin-3-yl and pyrazolidin-4-yl.
  • imidazolinyl as used herein includes imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl and imidazolin-5-yl.
  • pyrazolinyl as used herein includes 1-pyrazolin-3-yl, 1-pyrazolin-4-yl, 2-pyrazolin-1-yl, 2-pyrazolin-
  • dioxolanyl also known as “1 ,3-dioxolanyl” as used herein includes dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl.
  • dioxolyl also known as "1 ,3- dioxolyl” as used herein includes dioxol-2-yl, dioxol-4-yl and dioxol-5-yl.
  • oxazolidinyl as used herein includes oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl and oxazolidin-5-yl.
  • isoxazolidinyl as used herein includes isoxazolidin-2-yl, isoxazolidin-3-yl, isoxazolidin-4-yl and isoxazolidin-5-yl.
  • oxazolinyl as used herein includes 2-oxazolinyl-2-yl, 2-oxazolinyl-4-yl, 2- oxazolinyl-5-yl, 3-oxazolinyl-2-yl, 3-oxazolinyl-4-yl, 3-oxazolinyl-5-yl, 4-oxazolinyl-2-yl, 4-oxazolinyl-3- yl, 4-oxazolinyl-4-yl and 4-oxazolinyl-5-yl.
  • isoxazolinyl as used herein includes 2- isoxazolinyl-3-yl, 2-isoxazolinyl-4-yl, 2-isoxazolinyl-5-yl, 3-isoxazolinyl-3-yl, 3-isoxazolinyl-4-yl, 3- isoxazolinyl-5-yl, 4-isoxazolinyl-2-yl, 4-isoxazolinyl-3-yl, 4-isoxazolinyl-4-yl and 4-isoxazolinyl-5-yl.
  • thiazolidinyl as used herein includes thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl and thiazolidin-5-yl.
  • isothiazolid inyl as used herein includes isothiazolidin-2-yl, isothiazolidin- 3-yl, isothiazolidin-4-yl and isothiazolidin-5-yl.
  • chromanyl as used herein includes chroman-2-yl, chroman-3-yl, chroman-4-yl, chroman-5-yl, chroman-6-yl, chroman-7-yl and chroman- 8-yl.
  • thiazolinyl as used herein includes 2-thiazolinyl-2-yl, 2-thiazolinyl-4-yl, 2-thiazolinyl-
  • isothiazolinyl as used herein includes 2- isothiazolinyl-3-yl, 2-isothiazolinyl-4-yl, 2-isothiazolinyl-5-yl, 3-isothiazolinyl-3-yl, 3-isothiazolinyl-4-yl, 3-isothiazolinyl-5-yl, 4-isothiazolinyl-2-yl, 4-isothiazolinyl-3-yl, 4-isothiazolinyl-4-yl and 4- isothiazolinyl-5-yl.
  • piperidyl also known as “piperidinyl” as used herein includes piperid-1- yl, piperid-2-yl, piperid-3-yl and piperid-4-yl.
  • dihydropyridinyl as used herein includes 1 ,2- dihydropyridin-1-yl, 1 ,2-dihydropyridin-2-yl, 1 ,2-dihydropyridin-3-yl, 1 ,2-dihydropyridin-4-yl, 1 ,2- dihydropyridin-5-yl, 1 ,2-dihydropyridin-6-yl, 1 ,4-dihydropyridin-1-yl, 1 ,4-dihydropyridin-2-yl, 1 ,4- dihydropyridin-3-yl, 1 ,4-dihydropyridin-4-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-4-yl,
  • tetrahydropyridinyl as used herein includes 1 ,2,3,4-tetrahydropyridin- 1 -yl, 1 ,2,3,4-tetrahydropyridin-2-yl, 1 ,2,3,4-tetrahydropyridin-3-yl, 1 ,2,3,4-tetrahydropyridin-4-yl, 1 ,2,3,4-tetrahydropyridin-5-yl, 1 ,2,3,4-tetrahydropyridin-6-yl, 1 ,2,3,6-tetrahydropyridin-1-yl, 1 ,2,3,6- tetrahydropyridin-2-yl, 1 ,2,3,6-tetrahydropyridin-3-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, 1 ,2,3,6- tetrahydropyridin-5-yl, 1 ,2,3,6-tetrahydropyri
  • tetrahydropyranyl also known as “oxanyl” or "tetrahydro-2H-pyranyl”, as used herein includes tetrahydropyran-2-yl, tetrahydropyran-3- yl and tetrahydropyran-4-yl.
  • the term "2H-pyranyl” as used herein includes 2H-pyran-2-yl, 2H-pyran- 3-yl, 2H-pyran-4-yl, 2H-pyran-5-yl and 2H-pyran-6-yl.
  • the term “4H-pyranyl” as used herein includes 4H-pyran-2-yl, 4H-pyran-3-yl and 4H-pyran-4-yl.
  • 3,4-dihydro-2H-pyranyl as used herein includes 3,4-dihydro-2H-pyran-2-yl, 3,4-dihydro-2H-pyran-3-yl, 3,4-dihydro-2H-pyran-4-yl, 3,4- dihydro-2H-pyran-5-yl and 3,4-dihydro-2H-pyran-6-yl.
  • 3,6-dihydro-2H-pyranyl as used herein includes 3,6-dihydro-2H-pyran-2-yl, 3,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl, 3,6-dihydro-2H-pyran-5-yl and 3,6-dihydro-2H-pyran-6-yl.
  • tetrahydrothiophenyl as used herein includes tetrahydrothiophen-2-yl, tetrahydrothiophenyl -3-yl and tetrahydrothiophenyl -4-yl.
  • 2H-thiopyranyl as used herein includes 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H- thiopyran-4-yl, 2H-thiopyran-5-yl and 2H-thiopyran-6-yl.
  • 4H-thiopyranyl as used herein includes 4H-thiopyran-2-yl, 4H-thiopyran-3-yl and 4H-thiopyran-4-yl.
  • 3,4-dihydro-2H- thiopyranyl as used herein includes 3,4-dihydro-2H-thiopyran-2-yl, 3,4-dihydro-2H-thiopyran-3-yl, 3,4-dihydro-2H-thiopyran-4-yl, 3,4-dihydro-2H-thiopyran-5-yl and 3,4-dihydro-2H-thiopyran-6-yl.
  • 3-dihydro-2H-thiopyranyl as used herein includes 3,6-dihydro-2H-thiopyran-2-yl, 3,6- dihydro-2H-thiopyran-3-yl, 3,6-dihydro-2H-thiopyran-4-yl, 3,6-dihydro-2H-thiopyran-5-yl and 3,6- dihydro-2H-thiopyran-6-yl.
  • piperazinyl also known as "piperazidinyl” as used herein includes piperazin-1-yl and piperazin-2-yl.
  • morpholinyl as used herein includes morpholin-2-yl, morpholin-3-yl and morpholin-4-yl.
  • thiomorpholinyl as used herein includes thiomorpholin-2-yl, thiomorpholin-3-yl and thiomorpholin-4-yl.
  • dioxanyl as used herein includes 1 ,2-dioxan-3-yl, 1 ,2-dioxan-4-yl, 1 ,3-dioxan-2-yl, 1 ,3-dioxan-4-yl, 1 ,3-dioxan-5-yl and 1 ,4-dioxan-2-yl.
  • dithianyl as used herein includes 1 ,2-dithian-3-yl, 1 ,2-dithian-4-yl, 1 ,3- dithian-2-yl, 1 ,3-dithian-4-yl, 1 ,3-dithian-5-yl and 1 ,4-dithian-2-yl.
  • oxathianyl as used herein includes oxathian-2-yl and oxathian-3-yl.
  • trioxanyl as used herein includes 1 ,2,3- trioxan-4-yl, 1 ,2,3-trioxay-5-yl, 1 ,2,4-trioxay-3-yl, 1 ,2,4-trioxay-5-yl, 1 ,2,4-trioxay-6-yl and 1 ,3,4- trioxay-2-yl.
  • azepanyl as used herein includes azepan-1-yl, azepan-2-yl, azepan-1-yl, azepan-3-yl and azepan-4-yl.
  • homoopiperazinyl as used herein includes homopiperazin-1- yl, homopiperazin-2-yl, homopiperazin-3-yl and homopiperazin-4-yl.
  • indolinyl as used herein includes indolin-1-yl, indolin-2-yl, indolin-3-yl, indolin-4-yl, indolin-5-yl, indolin-6-yl, and indolin- 7-yl.
  • quinolizinyl as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3- yl and quinolizidin-4-yl.
  • isoindolinyl as used herein includes isoindolin-1-yl, isoindolin-2-yl, isoindolin-3-yl, isoindolin-4-yl, isoindolin-5-yl, isoindolin-6-yl, and isoindolin-7-yl.
  • 3H- indolyl as used herein includes 3H-indol-2-yl, 3H-indol-3-yl, 3H-indol-4-yl, 3H-indol-5-yl, 3H-indol-6- yl, and 3H-indol-7-yl.
  • quinolizinyl as used herein includes quinolizidin-1-yl, quinolizidin-2- yl, quinolizidin-3-yl and quinolizidin-4-yl.
  • quinolizinyl as used herein includes quinolizidin- 1 -yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl.
  • tetrahydroquinolinyl as used herein includes tetrahydroquinolin-1-yl, tetrahydroquinolin-2-yl, tetrahydroquinolin-3-yl, tetrahydroquinolin-4-yl, tetrahydroquinolin-5-yl, tetrahydroquinolin-6-yl, tetrahydroquinolin-7-yl and tetrahydroquinolin-8-yl.
  • tetrahydroisoquinolinyl as used herein includes tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, tetrahydroisoquinolin-5-yl, tetrahydroisoquinolin-6-yl, tetrahydroisoquinolin-7-yl and tetrahydroisoquinolin-8-yl.
  • 1 H-pyrrolizine as used herein includes 1 H-pyrrolizin-1-yl, 1 H-pyrrolizin-2-yl, 1 H-pyrrolizin-3-yl, 1 H-pyrrolizin-5-yl, 1 H-pyrrolizin-6-yl and 1 H-pyrrolizin-7-yl.
  • 3H-pyrrolizine as used herein includes 3H-pyrrolizin-1-yl, 3H- pyrrolizin-2-yl, 3H-pyrrolizin-3-yl, 3H-pyrrolizin-5-yl, 3H-pyrrolizin-6-yl and 3H-pyrrolizin-7-yl.
  • heterocyclylene when used in conjunction with a heterocyclyl group, i.e. "heterocyclylene”, this is intended to mean the heterocyclyl group as defined herein having two single bonds as points of attachment to other groups.
  • heterocyclylalkyl as a group or part of a group, means an alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one heterocyclyl as defined herein.
  • Such rings may be fused to an aryl, cycloalkyi, heteroaryl or heterocyclyl ring.
  • Non-limiting examples of such heteroaryl include: pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, imidazo[2,1-b][1 ,3]thiazolyl, thieno[3,2-b]furanyl, thieno[3,2-b]thiophenyl, thieno[2,3-d][1 ,3]thiazolyl, thieno[2,3-d]imidazolyl,
  • pyrrolyl (also called azolyl) as used herein includes pyrrol-1-yl, pyrrol-2-yl and pyrrol-3-yl.
  • furanyl (also called “furyl”) as used herein includes furan-2-yl and furan-3-yl (also called furan-2-yl and furan-3-yl).
  • thiophenyl (also called “thienyl”) as used herein includes thiophen-2-yl and thiophen-3-yl (also called thien-2-yl and thien-3-yl).
  • pyrazolyl (also called 1 H-pyrazolyl and 1 ,2-diazolyl) as used herein includes pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl and pyrazol-5-yl.
  • imidazolyl as used herein includes imidazol-1-yl, imidazol-2-yl, imidazol- 4-yl and imidazol-5-yl.
  • oxazolyl (also called 1 ,3-oxazolyl) as used herein includes oxazol-
  • isoxazolyl also called 1 ,2-oxazolyl
  • isoxazolyl includes isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl.
  • thiazolyl also called 1 ,3- thiazolyl
  • thiazol-2-yl includes thiazol-2-yl, thiazol-4-yl and thiazol-5-yl (also called 2-thiazolyl, 4- thiazolyl and 5-thiazolyl).
  • isothiazolyl (also called 1 ,2-thiazolyl) as used herein includes isothiazol-3-yl, isothiazol-4-yl, and isothiazol-5-yl.
  • trimazolyl as used herein includes 1 H- triazolyl and 4H-1 ,2,4-triazolyl
  • 1 H-triazolyl includes 1 H-1 ,2,3-triazol-1-yl, 1 H-1 ,2,3-triazol-4-yl, 1 H- 1 ,2,3-triazol-5-yl, 1 H-1 ,2,4-triazol-1-yl, 1 H-1 ,2,4-triazol-3-yl and 1 H-1 ,2,4-triazol-5-yl.
  • 41-1-1 ,2,4- triazolyl includes 4H-1 ,2,4-triazol-4-yl, and 4H-1 ,2,4-triazol-3-yl.
  • oxadiazolyl as used herein includes 1 ,2,3-oxadiazol-4-yl, 1 ,2,3-oxadiazol-5-yl, 1 ,2,4-oxadiazol-3-yl, 1 ,2,4-oxadiazol-5-yl, 1 ,2,5-oxadiazol-3-yl and 1 ,3,4-oxadiazol-2-yl.
  • thiadiazolyl as used herein includes 1 ,2,3- thiadiazol-4-yl, 1 ,2,3-thiadiazol-5-yl, 1 ,2,4-thiadiazol-3-yl, 1 ,2,4-thiadiazol-5-yl, 1 ,2,5-thiadiazol-3-yl (also called furazan-3-yl) and 1 ,3,4-thiadiazol-2-yl.
  • tetrazolyl as used herein includes 1 H- tetrazol-1-yl, 1 H-tetrazol-5-yl, 2H-tetrazol-2-yl, and 2H-tetrazol-5-yl.
  • oxatriazolyl as used herein includes 1 ,2,3,4-oxatriazol-5-yl and 1 ,2,3,5-oxatriazol-4-yl.
  • thiatriazolyl as used herein includes 1 ,2,3,4-thiatriazol-5-yl and 1 ,2,3,5-thiatriazol-4-yl.
  • pyridinyl also called “pyridyl” as used herein includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl (also called 2-pyridyl, 3- pyridyl and 4-pyridyl).
  • pyrimidyl as used herein includes pyrimid-2-yl, pyrimid-4-yl, pyrimid-5-yl and pyrimid-6-yl.
  • pyrazinyl as used herein includes pyrazin-2-yl and pyrazin-
  • pyridazinyl as used herein includes pyridazin-3-yl and pyridazin-4-yl.
  • oxazinyl also called “1 ,4-oxazinyl” as used herein includes 1 ,4-oxazin-4-yl and 1 ,4-oxazin-5-yl.
  • dioxinyl also called “1 ,4-dioxinyl” as used herein includes 1 ,4-dioxin-2-yl and 1 ,4-dioxin- 3-yl.
  • thiazinyl (also called “1 ,4-thiazinyl”) as used herein includes 1 ,4-thiazin-2-yl, 1 ,4- thiazin-3-yl, 1 ,4-thiazin-4-yl, 1 ,4-thiazin-5-yl and 1 ,4-thiazin-6-yl.
  • triazinyl as used herein includes 1 ,3,5-triazin-2-yl, 1 ,2,4-triazin-3-yl, 1 ,2,4-triazin-5-yl, 1 ,2,4-triazin-6-yl, 1 ,2,3-triazin-4-yl and 1 ,2,3-triazin-5-yl.
  • imidazo[2,1-b][1 ,3]thiazolyl includes imidazo[2,1- b][1 ,3]thiazoi-2-yl, imidazo[2,1-b][1 ,3]thiazol-3-yl, imidazo[2,1-b][1 ,3]thiazol-5-yl and imidazo[2,1- b][1 ,3]thiazol-6-yl.
  • thieno[3,2-b]furanyl as used herein includes thieno[3,2-b]furan-2-yl, thieno[3,2-b]furan-3-yl, thieno[3,2-b]furan-4-yl, and thieno[3,2-b]furan-5-yl.
  • thieno[3,2- b]thiophenyl as used herein includes thieno[3,2-b]thien-2-yl, thieno[3,2-b]thien-3-yl, thieno[3,2- b]thien-5-yl and thieno[3,2-b]thien-6-yl.
  • thieno[2,3-d][1 ,3]thiazolyl as used herein includes thieno[2,3-d][1 ,3]thiazol-2-yl, thieno[2,3-d][1 ,3]thiazol-5-yl and thieno[2,3-d][1 ,3]thiazol-6-yl.
  • thieno[2,3-d]imidazolyl as used herein includes thieno[2,3-d]imidazol-2-yl, thieno[2,3-d]imidazol-4- yl and thieno[2,3-d]imidazol-5-yl.
  • tetrazolo[1 ,5-a]pyridinyl as used herein includes tetrazolo[1 ,5-a]pyridine-5-yl, tetrazolo[1 ,5-a]pyridine-6-yl, tetrazolo[1 ,5-a]pyridine-7-yl, and tetrazolo[1 ,5-a]pyridine-8-yl.
  • indolyl as used herein includes indol-1-yl, indol-2-yl, indol-3- yl,-indol-4-yl, indol-5-yl, indol-6-yl and indol-7-yl.
  • indolizinyl as used herein includes indolizin-1-yl, indolizin-2-yl, indolizin-3-yl, indolizin-5-yl, indolizin-6-yl, indolizin-7-yl, and indolizin-8-yl.
  • isoindolyl as used herein includes isoindol-1-yl, isoindol-2-yl, isoindol-3-yl, isoindol-4-yl, isoindol-5-yl, isoindol-6-yl and isoindol-7-yl.
  • benzofuranyl also called benzo[b]furanyl
  • benzofuran-2-yl benzofuran-3-yl
  • benzofuran-4-yl benzofuran-5-yl
  • benzofuran-6-yl benzofuran-7-yl
  • isobenzofuranyl also called benzo[c]furanyl
  • isobenzofuran-1-yl isobenzofuran-3-yl
  • isobenzofuran-4-yl isobenzofuran-5-yl
  • benzothiophenyl (also called benzo[b]thienyl) as used herein includes 2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5- benzo[b]thiophenyl, 6-benzo[b]thiophenyl and -7-benzo[b]thiophenyl (also called benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl, benzothien-6-yl and benzothien-7-yl).
  • isobenzothiophenyl also called benzo[c]thienyl
  • isobenzothien-1-yl isobenzothien-3-yl
  • isobenzothien-4-yl isobenzothien-5-yl
  • isobenzothien-6-yl isobenzothien-7- yl.
  • indazolyl (also called 1 H-indazolyl or 2-azaindolyl) as used herein includes 1 H-indazol- 1-yl, 1 H-indazol-3-yl, 1 H-indazol-4-yl, 1 H-indazol-5-yl, 1 H-indazol-6-yl, 1 H-indazol-7-yl, 2H-indazol- 2-yl, 2H-indazol-3-yl, 2H-indazol-4-yl, 2H-indazol-5-yl, 2H-indazol-6-yl, and 2H-indazol-7-yl.
  • benzimidazolyl as used herein includes benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl and benzimidazol-7-yl.
  • 1 ,2-benzisoxazolyl as used herein includes 1 ,2-benzisoxazol-3- yl, 1 ,2-benzisoxazol-4-yl, 1 ,2-benzisoxazol-5-yl, 1 ,2-benzisoxazol-6-yl and 1 ,2-benzisoxazol-7-yl.
  • 2,1-benzisoxazolyl as used herein includes 2,1-benzisoxazol-3-yl, 2,1-benzisoxazol-4-yl, 2,1-benzisoxazol-5-yl, 2,1-benzisoxazol-6-yl and 2,1-benzisoxazol-7-yl.
  • the term "1 ,3- benzothiazolyl” as used herein includes 1 ,3-benzothiazol-2-yl, 1 ,3-benzothiazol-4-yl, 1 ,3- benzothiazol-5-yl, 1 ,3-benzothiazol-6-yl and 1 ,3-benzothiazol-7-yl.
  • the term "1 ,2-benzoisothiazolyl” as used herein includes 1 ,2-benzisothiazol-3-yl, 1 ,2-benzisothiazol-4-yl, 1 ,2-benzisothiazol-5-yl, 1 ,2- benzisothiazol-6-yl and 1 ,2-benzisothiazol-7-yl.
  • 2,1-benzoisothiazolyl as used herein includes 2,1-benzisothiazol-3-yl, 2,1-benzisothiazol-4-yl, 2,1-benzisothiazol-5-yl, 2,1-benzisothiazol- 6-yl and 2,1-benzisothiazol-7-yl.
  • benzotriazolyl as used herein includes benzotriazol-1-yl, benzotriazol-4-yl, benzotriazol-5-yl, benzotriazol-6-yl and benzotriazol-7-yl.
  • 1 ,2,3- benzoxadiazolyl as used herein includes 1 ,2,3-benzoxadiazol-4-yl, 1 ,2,3-benzoxadiazol-5-yl, 1 ,2,3- benzoxadiazol-6-yl and 1 ,2,3-benzoxadiazol-7-yl.
  • 2,1 ,3-benzoxadiazolyl as used herein includes 2, 1 ,3-benzoxadiazol-4-yl, 2, 1 ,3-benzoxadiazol-5-yl, 2, 1 ,3-benzoxadiazol-6-yl and 2, 1 ,3- benzoxadiazol-7-yl.
  • 1 ,2,3-benzothiadiazolyl as used herein includes 1 ,2,3- benzothiadiazol-4-yl, 1 ,2,3-benzothiadiazol-5-yl, 1 ,2,3-benzothiadiazol-6-yl and 1 ,2,3- benzothiadiazol-7-yl.
  • 2,1 ,3-benzothiadiazolyl as used herein includes 2, 1 ,3- benzothiadiazol-4-yl, 2, 1 ,3-benzothiadiazol-5-yl, 2,1 ,3-benzothiadiazol-6-yl and 2, 1 ,3- benzothiadiazol-7-yl.
  • thienopyridinyl as used herein includes thieno[2,3-b]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2-c]pyridinyl and thieno[3,2-b]pyridinyl.
  • purinyl as used herein includes purin-2-yl, purin-6-yl, purin-7-yl and purin-8-yl.
  • imidazo[1 ,2-a]pyridinyl includes imidazo[1 ,2-a]pyridin-2-yl, imidazo[1 ,2-a]pyridin-3-yl, imidazo[1 ,2-a]pyridin-4-yl, imidazo[1 ,2-a]pyridin-5-yl, imidazo[1 ,2-a]pyridin-6-yl and imidazo[1 ,2-a]pyridin-7-yl.
  • 1 ,3- benzodioxolyl includes 1 ,3-benzodioxol-4-yl, 1 ,3-benzodioxol-5-yl, 1 ,3-benzodioxol- 6-yl, and 1 ,3-benzodioxol-7-yl.
  • quinolinyl as used herein includes quinolin-2-yl, quinolin-3- yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl and quinolin-8-yl.
  • isoquinolinyl as used herein includes isoquinolin-1-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6- yl, isoquinolin-7-yl and isoquinolin-8-yl.
  • cinnolinyl as used herein includes cinnolin-3-yl, cinnolin-4-yl, cinnolin-5-yl, cinnolin-6-yl, cinnolin-7-yl and cinnolin-8-yl.
  • quinazolinyl as used herein includes quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl and quinazolin-8-yl.
  • quinoxalinyl as used herein includes quinoxalin-2-yl, quinoxalin-5-yl, and quinoxalin-6-yl.
  • heteroarylene when used in conjunction with a heteroaryl group, i.e. "heteroarylene”, this is intended to mean the heteroaryl group as defined herein having two single bonds as points of attachment to other groups.
  • heteroarylalkyl as a group or part of a group, means an alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one heteroaryl as defined herein.
  • alkylamino refers to a group of formula -N(R°)(R ) wherein R° and R are each independently selected from hydrogen, or Ci- 6 alkyl, wherein at least one of R° or R is Ci- 6 alkyl.
  • alkylamino include mono-alkyl amino group (e.g. mono-Ci- 6 alkylamino group such as methylamino and ethylamino), and di-alkylamino group (e.g. di- alkylamino group such as dimethylamino and diethylamino).
  • Non-limiting examples of suitable mono- or di-Ci- 6 alkylamino groups include n-propylamino, isopropylamino, n-butylamino, / ' -butylamino, sec- butylamino, f-butylamino, pentylamino, n-hexylamino, di-n-propylamino, di-/-propylamino, ethylmethylamino, methyl-n-propylamino, methyl-/ ' -propylamino, n-butylmethylamino, /- butylmethylamino, f-butylmethylamino, ethyl-n-propylamino, ethyl-/ ' -propylamino, n-butylethylamino, i-butylethylamino, f-butylethylamino, di-n-but
  • di- or di-arylamino refers to a group of formula -N(R q )(R r ) wherein R q and R r are each independently selected from hydrogen, aryl, or alkyl, wherein at least one of R q or R r is C6-i2aryl.
  • di- or di-cycloalkylamino refers to a group of formula -N(R s )(R l ) wherein R s and R l are each independently selected from hydrogen, cycloalkyl, or alkyl, wherein at least one of R s or R l is cycloalkyl.
  • aminoalkyl refers to a group of formula -R a -NR°R wherein R a is Ci- 6 alkylene, R° is hydrogen or alkyl as defined herein, and R is hydrogen or Ci- 6 alkyl as defined herein.
  • mono- or di-heteroarylamino refers to a group of formula -N(R U )(R V ) wherein R u and R v are each independently selected from hydrogen, heteroaryl, or Ci- 6 alkyl, wherein at least one of R u or R v is heteroaryl as defined herein.
  • hydroxycarbonylalkyl refers to a group of formula -R a -COOH, wherein R a is alkylene as defined herein.
  • alkyloxycarbonyl refers to a group of formula -COO-R b , wherein R b is alkyl as defined herein.
  • di- or dialkylaminocarbonyl refers to a group of formula -CONR°R wherein R°R are each independently selected from hydrogen, or Ci- 6 alkyl, wherein at least one of R° or R p is d -6 alkyl.
  • alkylcarbonyl refers to a group of formula -CO-R b , wherein R b is alkyl as defined herein.
  • alkylcarbonylamino refers to a group of formula -NR°-CO-R b , wherein R° is selected from hydrogen, or alkyl and R b is alkyl as defined herein.
  • di or di-alkylaminocarbonylCi- 6 alkyl refers to a group of formula -R a -CONR°R wherein R°R are each independently selected from hydrogen, or alkyl, wherein at least one of R° or R is alkyl, and R a is alkylene as defined herein.
  • a leaving group means a chemical group which is susceptible to be displaced by a nucleophile or cleaved off or hydrolyzed in basic or acidic conditions.
  • a leaving group is selected from a halogen atom (e.g., CI, Br, I) or a trihalomethyl group (e.g. CCI 3 , Cl 3 , CBr 3 ).
  • a saturated or unsaturated 3- , 4- , 5- , 6- or 7-membered ring encompasses saturated or unsaturated carbon only membered rings, as well as saturated or unsaturated heteroatoms containing rings.
  • a saturated 3- , 4- , 5- , 6- or 7- carbon membered ring refers to saturated carbon only membered ring such as C 3- 7 cycloalkyl and C 3-7 cycloalkylene.
  • the term "compounds of the invention” or a similar term is meant to include the compounds of general formula (I) and any subgroup thereof. This term also refers to the compounds as depicted in Table 1 and their derivatives, N-oxides, salts, solvates, hydrates, stereoisomeric forms, racemic mixtures, tautomeric forms, optical isomers, analogues, pro- drugs, esters and metabolites, as well as their quaternized nitrogen analogues.
  • the N-oxide forms of said compounds are meant to comprise compounds wherein one or several nitrogen atoms are oxidized to the so-called N-oxide.
  • a 1 is selected from the group consisting of S; and O;
  • R 1 is selected from the group consisting of aryl; cycloalkyl; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyl; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • m is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyl; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyl; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ; 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyi; arylalkyl; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom
  • R 5 is selected from the group consisting of hydrogen, alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20
  • each Z 6 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • alkyl as a group or part of a group is Ci -6 alkyl
  • alkenyl as a group or part of a group is C 2-6 alkenyl
  • alkynyl as a group or part of a group
  • cycloalkyl as a group or part of a group
  • aryl as a group or part of a group, is C 6- i 2 aryl.
  • L is NR 5 and R 5 is selected from the group consisting of hydrogen, alkyl; aryl; cycloalkyl; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl.
  • R 6 is selected from the group consisting of hydrogen; alkyl; aryl; cycloalkyl; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl
  • R 7 is selected from the group consisting of hydrogen; alkyl; aryl; cycloalkyl; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl.
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; haloalkyl; arylalkyl; heterocyclylalkyl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 1 , preferably R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; arylalkyl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 1 , preferably R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 1 , preferably R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 2 °; and -NHC(0)NR 16 R 17 , preferably each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • R 2 is selected from the group consisting of arylalkyi; alkyl; cycloalkyi; aryl; heterocyclyl; heterocyclylalkyi; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ,
  • each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; cycloalkyl; aryl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 3 .
  • each Z 3 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 .
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyl; arylalkyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ; each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; - S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ; each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalky
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; - S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and - NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ; each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; - C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • n is an integer selected from 0, 1 , 2, or 3; each R 12 is independently selected from the group consisting of hydrogen; halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(O) 5 R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-member
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 13 is selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyl; cyano;
  • a 1 is S
  • R 1 is selected from the group consisting of aryl; cycloalkyl; heteroaryl; heterocyclyl; alkyl; arylalkyl; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; cycloalkyl; aryl; heterocyclyl; 30 heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; cycloalkyl; aryl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ; : 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyi; arylalkyi; arylcarbonylalkyi; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R is selected from the group consisting of hydrogen; alkyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 3 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20
  • each Z 7 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • a 1 is O
  • R 1 is selected from the group consisting of aryl; cycloalkyl; heteroaryl; heterocyclyl; alkyl; arylalkyl; heterocyclylalkyl; heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyl; alkyl; cycloalkyl; aryl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyl; hydrogen; alkyl; cycloalkyl; aryl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyi; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from
  • a 2 is selected from the group consisting of O; NR 9 ; NH; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; alkyl; cycloalkyl; arylalkyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyi; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, haloalkyl; haloalkyloxy; cycloalkyl; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyi; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyi; heteroaryl; heteroarylalkyi; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(O) R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R 5 is selected from the group consisting of hydrogen, alkyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 6 is selected from the group consisting of hydrogen; alkyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 7 is selected from the group consisting of hydrogen; alkyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heteroaryheterocyclyl, heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 3 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 4 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; - NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alkyl
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of alky
  • a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and a therapeutically effective amount of a compound according to any one of statements 1 to 28.
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitro en to which they are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyi; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 2 °; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 3 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; 19.
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitro en to which they are attached a moiety selected from the
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyi; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyi; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 5 ;
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; - N0 2 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; wherein each group can be unsubstituted or substituted with one or more Z 6 ;
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 15 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • alkyl is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyl; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyi; and heteroarylalkyi;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyi; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyi; heteroaryl; heteroarylalkyi; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; 19.
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 6 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; 19.
  • a compound for use according to any one of statements 30 or 31 wherein said compound is a compound according to any one of statements 1 to 29.
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which they are attached a moiety selected from the roup consisting ;
  • a 2 is selected from the group consisting of O; NR 9 ; CR 10 R 11 ; and S;
  • n is an integer selected from 0, 1 , 2, or 3;
  • n is an integer selected from 0, 1 , 2, or 3;
  • q is an integer selected from 0, 1 , 2, or 3;
  • r is an integer selected from 0, 1 , 2, or 3;
  • R 9 is selected from the group consisting of aryl; hydrogen; alkyl; cycloalkyi; arylalkyi; arylalkenyl; arylalkynyl; arylcarbonylalkyl; arylcarbonylthiocarbonyl; heterocyclyl; heterocyclylalkyl; heterocyclylcarbonylalkyl; heterocyclylcarbonylthiocarbonyl; heteroaryl; heteroarylalkyl; heteroarylcarbonylalkyl; heteroarylcarbonylthiocarbonyl; wherein each group can be unsubstituted or substituted with one or more Z 4 ;
  • R 10 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl
  • R 11 is selected from the group consisting of halo, hydrogen, alkyl, alkenyl; alkynyl; haloalkyl; haloalkyloxy; cycloalkyi; aryl; arylalkyl; hydroxyl; -NR 16 R 17 ; -OR 18 ; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl; carboxyl; -SR 19 ; cyano; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -
  • each R 12 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 12 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 13 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 13 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of
  • each R 14 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ;
  • each R 15 is independently selected from the group consisting of hydrogen; halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two R 15 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or hetero
  • R 4 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 5 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 6 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 7 is selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; aryl; cycloalkyi; arylalkyi; heterocyclyl; heteroaryl; heterocyclylalkyl; and heteroarylalkyl;
  • R 8 is selected from the group consisting of alkyl; hydroxyl; -OR 18 ; cycloalkyi; arylalkyi; heterocyclylalkyl; and heteroarylalkyl;
  • R 16 and R 17 form together with the nitrogen to which they are attached, a saturated or unsaturated 4-, 5-, or 6-membered ring, said saturated or unsaturated ring can be unsubstituted or substituted with one or more Z 7 ;
  • each Z 1 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryheterocyclyl, -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ;
  • each Z 2 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 2 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 3 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 3 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 4 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -NHS (0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 4 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 5 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyi; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 5 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 6 is independently selected from the group consisting of halo; -NO2; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 2 °; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 2 °; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 6 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • each Z 7 is independently selected from the group consisting of halo; -N0 2 ; aryl; cycloalkyl; cyano; hydroxyl; -OR 18 ; alkyl; haloalkyl; haloalkyloxy; arylalkyl; heteroaryl; heteroarylalkyl; heterocyclyl; heterocyclylalkyl; -NR 16 R 17 ; -SR 19 ; carboxyl; -C0 2 R 20 ; -C(0)NR 16 R 17 ; -C(0)R 20 ; -S(0)R 20 ; -S(0) 2 R 20 ; -S0 2 NR 16 R 17 ; -NHC(0)R 20 ; -N HS(0) 2 R 20 ; and -NHC(0)NR 16 R 17 ; or two Z 7 together with the atom to which they are attached can form a saturated or unsaturated 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of al
  • a 1 is selected from the group consisting of S; O; and NR 4 ;
  • R 1 is selected from the group consisting of aryl; cycloalkyi; heteroaryl; heterocyclyl; alkyl; alkenyl; alkynyl; haloalkyl; haloalkyloxy; arylalkyi; heterocyclylalkyl; heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 1 ;
  • R 2 is selected from the group consisting of arylalkyi; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 2 ;
  • R 3 is selected from the group consisting of arylalkyi; hydrogen; alkyl; alkenyl; alkynyl; cycloalkyi; aryl; arylalkenyl; arylalkynyl; heterocyclyl; heterocyclylalkyl; heteroaryl; and heteroarylalkyl; wherein each group can be unsubstituted or substituted with one or more Z 3 ;
  • R 2 and R 3 form together with the nitrogen to which the are attached a moiety selected from the

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Abstract

La présente invention décrit un composé de formule (I), son stéréoisomère, son énantiomère, son racémique, ou son tautomère tel que définis dans la revendication 1 (I) la présente invention concerne également un composé de formule (I), son stéréoisomère, son énantiomère, son racémique, ou son tautomère, tel que définis dans les revendications destiné à une utilisation comme médicament, en particulier destiné à une utilisation dans la prévention ou le traitement d'une maladie cellulaire proliférative.
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110511193A (zh) * 2019-08-27 2019-11-29 武汉工程大学 一种α-酮硫代酰胺类化合物及其合成方法
CN111138358A (zh) * 2019-12-17 2020-05-12 中国药科大学 Usp8抑制剂及其制备方法与应用
US10947242B2 (en) 2016-11-02 2021-03-16 Janssen Pharmaceutica, Nv [1,2,4]triazolo[1,5and#8208;A]pyrimidine compounds as PDE2 inhibitors
US10947239B2 (en) 2015-11-02 2021-03-16 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compound
US11053248B2 (en) 2016-11-02 2021-07-06 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidine compounds as PDE2 inhibitors
US11319321B2 (en) 2016-11-02 2022-05-03 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidine compounds as PDE2 inhibitors
CN117105821A (zh) * 2023-04-18 2023-11-24 重庆普佑制药有限公司 一种沙库比曲中间体的制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0721331A1 (fr) 1993-10-01 1996-07-17 Astra Aktiebolag Procede (i)
US6369087B1 (en) 1999-08-26 2002-04-09 Robert R. Whittle Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6369086B1 (en) 1997-09-05 2002-04-09 Smithkline Beecham Corporation Substituted oxidole derivatives as protein tyrosine and as protein serine/threonine kinase inhibitors
US6372733B1 (en) 1995-11-01 2002-04-16 Merck & Co., Inc. Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases
US6372778B1 (en) 1992-09-08 2002-04-16 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
CN102653619A (zh) * 2012-04-24 2012-09-05 南京林业大学 一种聚氯乙烯塑木复合材料板材及其制备方法
WO2017011666A1 (fr) 2015-07-14 2017-01-19 Bristol-Myers Squibb Company Méthode destinée à traiter le cancer à l'aide d'un inhibiteur des points de contrôle immunitaires

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6372778B1 (en) 1992-09-08 2002-04-16 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
EP0721331A1 (fr) 1993-10-01 1996-07-17 Astra Aktiebolag Procede (i)
US6372733B1 (en) 1995-11-01 2002-04-16 Merck & Co., Inc. Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases
US6369086B1 (en) 1997-09-05 2002-04-09 Smithkline Beecham Corporation Substituted oxidole derivatives as protein tyrosine and as protein serine/threonine kinase inhibitors
US6369087B1 (en) 1999-08-26 2002-04-09 Robert R. Whittle Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
CN102653619A (zh) * 2012-04-24 2012-09-05 南京林业大学 一种聚氯乙烯塑木复合材料板材及其制备方法
WO2017011666A1 (fr) 2015-07-14 2017-01-19 Bristol-Myers Squibb Company Méthode destinée à traiter le cancer à l'aide d'un inhibiteur des points de contrôle immunitaires

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
C.N. KAPANDA ET AL.: "Synthesis and pharmacological evaluation of 2,4-dinitroaryldithiocarbamate derivatives as novel monoacylglycerol lipase inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 55, 31 May 2012 (2012-05-31), pages 5774 - 5783, XP002759525 *
CLIN. CANCER RESEARCH, 2013, pages 1021 - 1034
E. L. ELIEL; S. H. WILEN; L. N. MANDER: "Stereochemistry of Organic Compounds", 1994, WILEY- INTERSCIENCE
HALEBLIAN, J PHARM SCI, vol. 64, no. 8, August 1975 (1975-08-01), pages 1269 - 1288
HARRIS T W ET AL: "AFFINITY OF 10-(4-METHYLPIPERAZINO)DIBENZ not B,F 3/4 OXEPINS FOR CLOZAPINEAND SPIROPERIDOL BINDING SITES IN RAT BRAIN", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 25, no. 7, 1 January 1982 (1982-01-01), pages 855 - 858, XP001012760, ISSN: 0022-2623, DOI: 10.1021/JM00349A018 *
IMS HEALTH INSTITUTE GLOBAL ONCOLOGY REPORT, June 2016 (2016-06-01)
K. R. MORRIS: "Polymorphism in Pharmaceutical Solids", 1995, MARCEL DEKKER
LI HONG-ZHENG ET AL: "Direct synthesis of [alpha]-ketothioamides from aryl methyl ketones and amines via I2-promoted sp3C-H functiona", TETRAHEDRON, vol. 70, no. 31, 20 May 2014 (2014-05-20), pages 4645 - 4651, XP028848193, ISSN: 0040-4020, DOI: 10.1016/J.TET.2014.05.045 *
N. H. HARTSHORNE; A. STUART: "Crystals and the Polarizing Microscope, 4th ed.", 1970, EDWARD ARNOLD
NATURE REVIEWS CLINICAL ONCOLOGY, 2013, pages 143 - 158
O. ALMARSSON; M. J. ZAWOROTKO, CHEM COMMUN, vol. 17, 2004, pages 1889 - 1896
STAHL; WERMUTH: "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", 2002, WILEY-VCH
T. W. GREENE; P. G. M. WUTS: "Protective Groups in Organic Chemistry", 1999, JOHN WILEY AND SONS
U. C. KASSÉHIN ET AL.: "Insight into the Willgerodt-Kindler reaction of gamma-haloacetophenone derivatives", ORG. CHEM. INT., 486540, 10 December 2014 (2014-12-10), pages 1 - 5, XP002759527 *
V. S. VELEZHEVA ET AL., J. HETEREOCYCLIC. CHEM., vol. 50, 1 January 2013 (2013-01-01), pages 225 - 236, XP002759526 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10947239B2 (en) 2015-11-02 2021-03-16 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compound
US10947242B2 (en) 2016-11-02 2021-03-16 Janssen Pharmaceutica, Nv [1,2,4]triazolo[1,5and#8208;A]pyrimidine compounds as PDE2 inhibitors
US11053248B2 (en) 2016-11-02 2021-07-06 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidine compounds as PDE2 inhibitors
US11319321B2 (en) 2016-11-02 2022-05-03 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidine compounds as PDE2 inhibitors
CN110511193A (zh) * 2019-08-27 2019-11-29 武汉工程大学 一种α-酮硫代酰胺类化合物及其合成方法
CN110511193B (zh) * 2019-08-27 2023-03-21 武汉工程大学 一种α-酮硫代酰胺类化合物及其合成方法
CN111138358A (zh) * 2019-12-17 2020-05-12 中国药科大学 Usp8抑制剂及其制备方法与应用
CN111138358B (zh) * 2019-12-17 2023-04-18 中国药科大学 Usp8抑制剂及其制备方法与应用
CN117105821A (zh) * 2023-04-18 2023-11-24 重庆普佑制药有限公司 一种沙库比曲中间体的制备方法

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