LV10096B - Substituted cyclic carbonyl compounds, their derivatives and use thereof as inhibitors of proteinases of retroviruses - Google Patents

Abstract

The invention applies to substituted cyclic carbonyls and their derivatives which are used as retrovirus protease inhibitors, pharmaceutical compositions containing these compounds and methods of curing viral infections using these compounds.

Description

LV 10096

I1TLE

Substituted Cyclic Carbonyls and Derivatives Thereof 5 Useful as Retroviral Protease Inhibitors FIELB..0F THE INVENTION ‘

This invention relates to substituted cyclic 10 carbonyls and derivatives thereof useuful as retroviral protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating virai infection.

15 BACKGROUND OF THE INVENTION

Current treatments for virai diseases usually involve administration of compounds that inhibit virai DNA synthesis. Current treatments for AIDS (Dagani, 20 Chem. Eng. Nevrs, November 23, 1987 pp. 41-49) involve administration of compounds such as 2',3'-dideoxycytidine, trisodium phosphonoformate, ammonium 21-tungsto-9-antimoniate, l-b-D-ribofuranoxyl-l,2,4-triazole-3-carboxamide, 3'-azido-3 *-deoxythymidine 25 (AZT), and adriamycin that inhibit virai DNA synthesis; compounds such as AL-721 and polymannoacetate vhich may prevent HIV from penetrating the host celi; and compounds which treat the opportunistic infections caused by the immunosupression resulting from HIV 30 infection. None of the current AIDS treatments have proven to be totally effective in treating and/or reversing the disease. In additioii, many of the compounds currently used to treat AIDS cause adverse side effects Including low platelet count, rēnai 35 toxicity, and bone marrow cytopenia. 2

Proteases are enzymes which cleave proteīns at specific peptide bonds. Many biological functions are controlled or mediated by proteases and their complementary protease inhibitors. For example, the 5 protease renin cleaves the peptide angiotensinogen to producē the peptide angiotensin I. Angiotensin I is further cleaved by the protease angiotensin converting enzyme (ACE) to form the hypotensive peptide angiotensin II. Inhibitors of renin and ACE are knovm to reduce 10 high blood pressure in vivo. Hovever, no therapeutically useful renin protease inhibitors have been developed, due to problems of oral availability and in vivo stability.

The genomes of retroviruses encode a protease that 15 is responsible for the proteolytic processing of one or more polyprotein precursors such as the pol and gag gene Products. See Kellink, Arch. Virol. 1 (1988). Retroviral proteases most conunonly process the gag precursor into the core proteins, and also process the 20 pol precursor into reverse transcriptase and retroviral protease.

The correčt processing of the precursor polyproteins by the retroviral protease is necessary for the assembly of the infectious virions. It has been 25 shown that in vitro routagenesis that producēs protease-defective virus leads to the production of immature core forms which lack infectivity. See Cravford, J. Virol. 51 899 (1985); Katoh et al., Virology 115 280 (1985). Therefore, retroviral protease inhibition provides an 30 attractive target for antiviral therapy. See Mitsuya, Natvre 221 775 (1987).

Moore, Biochem. Biophys. Res. Commun., 159 420 (1989) discloses peptidyl inhibitors of HIV protease. Erickson, European Patent Application No. W0 89/10752 3 LV 10096 discloses derivatives of peptides which are inhibitors of HIV protease. U.S. Patent No. 4,652,552 discloses methyl ketone derivatives of tetrapeptides as inhibitors of virai 5 proteases. Ū.S. Patent No. 4,644,055 discloses halomethyl derivatives of peptides as inhibitors of virai proteases. European Patent Application No. W0 87/07836 discloses L-glutamic acid gamma-monohydroxamate as an antiviral aģent. 10 The ability to inhibit a virai protease provides a method for blocking virai replication and therefore a treatment for virai diseases, such as AIDS, that may have fever side effects, be more efficacious, and be less prone to drug resistance when compared to current 15 treatments.

The topic of the present invention is substituted cyclic carbonyls and derivatives thereof, which compounds are capable of inhibiting virai protease and which compounds are believed to serve as a means of 20 combating virai diseases, such as AIDS. The substituted cyclic carbonyls and derivatives thereof of this invention provide significant improvements over protease inhibitors that are known in the art. A large number of compounds have been reported to be inhibitors of 25 proteases, such as renin, but these have suffered from lack of adequate bioavailability and are thus not useful as therapeutic aģents, particularly if oral administration is desired. This poor activity has been ascribed to the relatively high molecular veight of most 30 protease inhibitors, to inadequate solubility properties, and to the presence of a number of peptide bonds, which are vulnerable to cleavage by mammalian proteases in vivo and which generally cause the molecules to be extensively bound in human serum. The 35 substituted cyclic carbonyls and derivatives described 4 herein have a distinct advantage in this regard, in that they do not contain peptide bonds, are of low molecular veight, and can be hydrophilic yet stili inhibit the virai protease enzyme.

5 Additionally, known inhibitors of other non-HIV proteases do not inhibit HIV protease. The structure-activity requirements'of such inhibitors differ from those of HIV protease inhibitors. The substituted cyclic carbonyls and derivatives of the invention are 10 particularly useful as inhibitors of HIV protease and similar retroviral proteases.

Other HIV protease inhibitors have been reported, but to datē none have been shown to be clinically effective. This lack of utility is due in part to the 15 factors discussed above for renin inhibitors, particularly low bioavailability. The compounds of the invention offer a valuable solution to this problem in that they are of low molecular weight are therefore expected have good oral absorption properties in 20 mammals.

DETAILED DESCRIPTION OF THE INVENTION

There is provided by this invention a compound of 25 the formula (1):

(I) 30 or a pharmaceutically acceptable salt or prodrug form thereof vherein: 5 LV 10096 R4 and R7 are independently selected from the following groups: hydrogen; 5 Ci“Ce alkyl substituted with 0-3 R1*; C2-C8 alkenyl substituted with 0-3 R^·; C2-C8 alkynyl substituted with 0-3 R*1; C3-C8 cycloalkyl substituted with 0-3 R1*; C6~Cio bicycloalkyl substituted with 0-3 R**; 10 aryl substituted with 0-3 R12; a C6-C14 carbocyclic residue substituted with 0-3 R12; a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least 15 one nitrogen, oxygen or sulfur atom; R4A and R7A are independently selected from the folloving groups: 20 hydrogen; C1-C4 alkyl substituted vith halogen or C3.-C2 alkoxy; benzyl substituted with halogen or C1-C2 alkoxy; 25 R4 and R4a can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R*2; R^ and R^A can alternatively join to form a 5-7 membered 30 carbocyclic ring substituted with 0-2 R12; n is 0, 1, or 2; R^ is selected from fluoro, difluoro, *0/ C1-C3 alkyl or 35 -OR20; 6 R*>, when n is 1, is selected from: hydrogen, *0, fluoro/ difluoro, Cļ-C3 alkyl or -OR21; 5 r6, when n is 2, is independently selected from: hydrogen, *0, fluoro, difluoro, C1-C3 alkyl or -OR21; r5 and R® can alternatively join to form an epoxide ring; 10 R2® and R21 are independently selected from: hydrogen; C1-C6 alkyl substituted with 0-3 R11; 15 C3-C6 alkoxyalkyl substituted with 0-3 R11; C1-C6 alkylcarbonyl substituted with 0-3 R11;

Ci-C6 alkoxycarbonyl substituted with 0-3 R11; benzoyl substituted with 0-3 R12; . phenoxycarbonyl substituted vrith 0-3 R12; 20 phenylaminocarbonyl substituted with 0-3 R12;or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl; r11 is selected from one or more of the folloving: 25 keto, halogen, cyano, -NR13R14, -CO2R13, -0C(*0)R13, -OR13, C2-C6 alkoxyalkyl, -S(0)mR13, -NHC(~NH)NHR13, -C(*NH)NHR13, -C(=0)NR13R14, -NR14C(«0)R13, -NOR14, -NR14C<=0)0R14, 30 -0C(*0)NR13R14, -NR13C(»0)NR13R14, -NR14S02NR13R14 -NR14S02R13, -S02NR13R14, C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl; 7 LV 10096 1-3 amlno acids, linked together via amide bonds and linked to R* or R7 via the amine or carboxylate terminus; 5 a C5-C14 carbocyclic residue substituted with 0-3 R12; aryl substituted with 0-3 R12; or 10 a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 15 R12, when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C4 alkyl, C3-C6 20 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -NR^rH, C2-C6 alkoxyalkyl, C1-C4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl, C1-C4 25 alkylcarbonylamino, -SfOJmR1^, -SC^NR^rH, -NHS02R·*·*# -OCH2CO2H, 2-(1-morpholino) ethoxy; or a 5- or β-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from oxygen, nitrogen or 30 sulfur; « or R*2 may be a 3- or 4- carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6- membered ring being 8 optionally substituted on the aliphatic carbons vith halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, or -NR13R14; or, when R*2 ļs attached to a saturated carbon atom, it may be carbonyl or thiocarbonyl; 5 R12, when a substituent on nitrogen, is selected from one or more of the following: « phenyl, benzyl, phenethyl, hydroxy, C1-C4 10 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, -NR13R14, C2-C6 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 alkoxycarbonyl, Ci“C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl; 15 R13 is H, phenyl, benzyl or C1-C6 alkyl; R14 is H or C1-C4 alkyl; R13 and R14 can alternatively join to form -(CH2>4-, 20 - (CH2) 5-, -CH2CH2N(r15)CH2CH2~, or -CH2CH2OCH2CH2-; R15 is H or CH3; m is 0, 1 or 2; 25 W is selected from: -N(R22)C(«Z)N(R23)-; -N(R22)S(-0)N(R23)-; -OC(=Z)0-; 30 -N(R22)C(=Z)0-; -c(r25) (R26)C(«z)c(R27) (R28)-; -N(R22)C(“Z)C(R27) (R28)-; -C{R25MR26)C{»Z)0-; -n(r22)c(»o)C(-o)n(R23)-; -C(R25) (R26)C(F2)C(R27) (R28)-; 35 9 LV 10096 -C{R25) {R26)N(CH3) (O)C(R27) (R28)-; "C(R25) (R28)N(Or29)C(r27) (R28)-; -C<R25) (R28)C(-Z)S-; 5 vherein: Z is 0, S, or Nr24. R22 and R22 are independently selected from the 10 follovdng: hydrogen;

Ci~C8 alkyl substituted with 0-3 R^; C2-C8 alkenyl substituted with 0-3 R77; 15 C2-C8 alkynyl substituted with 0-3 R^·; C3-C8 cycloalkyl substituted with 0-3 R1*·; C6"Cio bicycloalkyl substituted with 0-3 R17; aryl substituted with 0-3 R12; a C6_Ci4 carbocyclic residue substituted with 0-3 20 R12; a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 25 R24 is selected from: hydroxy; amino; C1-C4 alkyl; C1-C4 alkoxy; C1-C4 aminoalkyl; r25 and R27 are independently selected from the folloving: 30 hydrogen; C1-C8 alkyl substituted with 0-3 R1*; C2“C8 alkenyl substituted with 0-3 R1*; C2-C8 alkynyl substituted with 0-3 R11; 35 C3-C8 cycloalkyl substituted with 0-3 R11; 10 C6“Cio bicycloalkyl substituted with 0-3 R11; aryl substituted with 0-3 R*2; a C6-C14 carbocyclic residue substituted with 0-3 Rl2; a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; R2^ and R2® are independently selected from: hydrogen; C1-C4 alkyl substituted with halogen or C1-C2 alkoxy; benzyl substituted with halogen or C1-C2 alkoxy; r29 is selected from: hydrogen; C1-C4 alkyl substituted with halogen or C1-C2 alkoxy; benzyl substituted with halogen or C1-C2 alkoxy; alternatively, R22, r25# or r26^ independently, can join with R^ or R4A to form a five- or six-membered fused heterocyclic, aromatic, or alicyclic ring substituted with 0-2 R12; and alternatively/ R2®, r27, or r28# independently, can join with R7 or R7a to form a five- or six-membered fused heterocyclic, aromatic, or alicyclic ring substituted with 0-2 R12; provided that: 11 LV 10096 when R4 is hydrogen, R7 is not hydrogen; when W is -0C(*Z)0-, R4 and R7 are not hydrogen; 5 when R4 is hydrogen, at least one of the folloving is not hydrogen: R22, r23, r25, R26, R27 and R28,

Preferred compounds of this invention are compounds 10 of the formula (I):

(I) 15 or a pharmaceutically acceptable salt or prodrug form thereof vherein: R4 and R7 are indepēndently selected from the following groups: 20 hydrogen; C1-C4 alkyl substituted with 0-3 R1*; C3-C4 alkenyl substituted with 0-3 R11; C3-C4 alkynyl substituted with 0-3 R^; 25 R4A and R7A are hydrogen; n is 0 or 1; 30 r5 is selected from fluoro, difluoro, “O, or -OR2^; 12 R® ls selected from: hydrogen, "O, fluoro, difluoro, or -0R21; R2^ and R2! are independently selected from: 5 hydrogen; C1-C6 alkylcarbonyl; C1-C6 alkoxycarbonyl; benzoyl; or 10 any group that, when ādministered to a mammalian subject, cleaves to form a free hydroxyl;

Rll is selected from one or more of the folloving: keto, halogen, cyano, -NRi3Rl4, -C02R13, -OC(-0)R13, -OR13, C2-C4 alkoxyalkyl, -S(0)mR13, Ci« C4 alkylf C2-C4 alkenyl, C3-C6 cycloalkyl; 20 a C5-C14 carbocyclic residue substituted with 0-3

Rl2; aryl substituted with 0-3 Rl2; or 25 a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 30 r!2, when a substituent on carbon, is selected from one^ or more of the folloving: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C4 alkyl, C3-C6 35 cycloalkyl, C3-C6 cycloalkylmethyl, C7-Cio arylalkyl, 13 LV 10096 C1-C4 alkoxy, -NR13R*4, C2-C6 alkoxyalkyl, C1-C4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl, C1-C4 5 alkylcarbonylamino, -S(0)mR13, -S02NR13R14, -NHSO2R14; or a 5- or 6-membered'heterocyclic ring containing from 1 to 4 heteroatoms selected from oxygen, nitrogen or 10 sulfur; or R12 roay be a 3- or 4- carbon Chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6- membered ring being 15 optionally substituted on the aliphatic carbons with halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, or - NR*3r14; or, when R12 is attached to a saturated carbon atom, it may be carbonyl or thiocarbonyl; 20 Rl2f when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkyl, C3-C6 25 cycloalkyl, C3-C6 cycloalkylmethyl, -NR13R14, C2~C$ alkoxyalkyl, C1-C4 haloalkyl, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl; R13 is H or Cl“C6 alkyl; 30 R*4 is H, Ci~C4 alkyl, or benzyl; R13 and R14 can alternatively join to form -(CH2)4“, “(CH2)5-r -CH2CH2N(R15)CH2CH2-f or -CH2CH2OCH2CH2*·; 35 14 R15 is H or CB3; n is 0, 1 or 2; 5 W is selected from: -N(R22)C(«Z)N(R23)-; -N(R22)C(*Z)0-; -C(R23) (R26)C(-Z)C(R27) <R28)-; 10 -N(R22)C(«Z)C(R27) (R28)-; -C(R25) (R26)C(«Z)0-; -N(R22)C(«0)C(«0)N(R23)-; -C (R25) (R26)C(F2)C(R27) (R28)-; 15 vherein: Z is 0; R22 and R2^ are independently selected from the 20 folloving: hydrogen;

Ci-Ce alkyl substituted with 0-3 R1*; C3-C8 alkenyl substituted with 0-3 R11; 25 C3-C8 alkynyl substituted with 0-3 R*1; C3-C6 cycloalkyl substituted with 0-3 R^·; R25 and R27 are independently selected from the following: 30 hydrogen; C1-C8 alkyl substituted with 0-3 R11; C2-C8 alkenyl substituted with 0-3 R**; C3-C8 alkynyl substituted with 0-3 R^; 35 15 LV 10096 R26 and R28 are hydrogen;. provided that: 5 when R4 is hydrogenf R7 is not hydrogen; when W is -0C(*Z)0-, R4 and R7 are not hydrogen; when R4 is hydrogen, at least one of the follovdng 10 is not hydrogen: R22, R23, R2^, r26# r27 an(ļ r28#

Further preferred compounds of the invention of formula (I) are compounds of formula (II): 15

R4 R5 (II) 20 or a pharmaceutically acceptable salt or prodrug form thereof vherein: R4 and R7 are independently selected from the folloving groups: 25 hydrogen; C1-C4 alkyl substituted with 0-3 R11; C3-C4 alkenyl substituted with 0-3 R^; 30 r5 is -OR2(>; R® is hydrogen or -OR21; 16 R20 and R21 are independently hydrogen or any group thatf when administered to a mammalian subject, cleaves to form a free hydroxyl; 5

Rll is selected from one or more of the folloving: keto, halogen, -Nr13r14, -OR 13, C2“C4 alkoxyalkyl, C3.-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl; 10 aryl substituted with 0-3 Ri2; or a heterocyclic ring system substituted with 0-2 Ri2, composed of 5 to 10 atoms including at least 15 one nitrogen, oxygen or sulfur atom; r!2# when a substituent on carbon, is selected from one or more of the folloving: 20 phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, C1-C4 alkyl, C7-C10 arylalkyl, C1-C4 alkoxy, -NrI^rI^, methylenedioxy/ C1-C4 haloalkyl, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylamino; or 25 a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoras selected from oxygen, nitrogen or sulfur; 30 Rl2» when a substituent on nitrogen, is selected from 4 benzyl or methyl; R13 is H or C1-C2 alkyl; 35

Ri4 is H or C1-C2 alkyl; 17 LV 10096 R*3 and R14 can alternatively join to form ~(CH2)4-, -(CH2)5, -CH2CH2N(R15)CH2CH2-, or -CH2CH2OCH2CR2-; 5 W is selected from: -N(R22)C(«Z)N(R23)-; -C(R23) (R26)C(=Z)C(R27) (R28)-; -N(R22)C(«Z)C(R27)(R28)-; 10 -C(R25)(R26)C{«Z)0-; vherein: Z is 0; 15 R22 and R23 are independently selected from the folloving: hydrogen; 20 C1-C4 alkyl substituted with 0-3 R^; C3-C4 alkenyl substituted with 0^3 R^·; R25 and R27 are independently selected from the folloving: 25 hydrogen; C1-C4 alkyl substituted with 0-3 R^·; C3-C4 alkenyl substituted with 0-3 R11; 30 R26 and R28 are hydrogen; provided that: when R^ is hydrogen, R7 is not hydrogen; 35 18 when R4 is hydrogen, at least one of the folloving is not hydrogen: R22, r23# r25# r26# r27 ancj r28. 5 More preferred coropounds of the present invention are compounds of the further preferred scope above, wherein: R4 and R7 are independently selected from the folloving 10 groups: hydrogen; C1-C3 alkyi substituted with 0-1 R11; 15 R5 is -OR20; R*> is hydrogen or -OR2*; R20 and R21 are independently hydrogen or any group 20 that, when administered to a mammaiian subject, cleaves to form a free hydroxyl; R1* is selected from one or more of the following: 25 halogen, -OR13, C1-C4 alkyl, C5-C6 cycloalkyl; aryl substituted with 0-2 R12; or 30 a heterocydic ring system chosen from pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl/ pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, indolyl, quinolinyl/ isoquinolinyl; 19 LV 10096 R32, when a substituent. on carbon, 1s selected from one or more of the folloving: benzyloxy, halogen, methyl, C1-C4 alkoxy,CF3, 2-(l-5 morpholino)ethoxy; or R*2, when a substituent on nitrogen, is methyl; R*3 is h or methyl; 10 R*4 is H or methyl; R33 and R3* can alternatively join to form -(CH2)4-, -<CH2)5, -CH2CH2N(R15)CH2CH2-, or -CH2CH2OCH2CH2-; 15 W is -N(R22)C(=0)N(R23)-; wherein: 20 R22 and R23 are independently selected from the follovdng: hydrogen; C1-C4 alkyl substituted with 0-1 R^·; 25 C3-C4 alkenyl substituted with 0-1 R*3; provided that: when R^ is hydrogen, R2 is not hydrogen; when R^ is hydrogen, at least one of the following is not hydrogen: R22 and R23. 30 20

Specifically preferred are compounds of formula

O (Ila): R^N^^NR23

(Ila) selected from the group consisting of: the compound of formula (Ila) vherein R22 is H and R23 is H; 10 the compound of formula (Ila) vherein R22 is allyl and R23 is allyl; the compound of formula (Ila) vherein R22 is 3,7-15 dimethyl-l-octyl and R23 is 3,7-dimethyl-l-octyl; the compound of formula (Ila) vherein R22 is CH2CH2OCH2CH2OCH3 and R23 is CH2CH2OCH2CH2OCH3; 20 the compound of formula (Ila) vherein R22.is 3,7- dimethyl-l-octyl and R23 is H; the compound of formula (Ila) vherein R22 is (CH2CH2O)3CH3 and R23 is H; 25 the compound of formula (Ila) vherein R22 is (CH2CH2O)3CH3 and R23 is (CH2CH2O)3CH3; the compound of formula (Ila) vherein R22 is 30 CH2CH2OH and R23 is CH2CH2NHCH(CH(CH3)2)C(«0)0-benzyl; 21 LV 10096 the compound of formula (Ila) vherein R22 is CH2CH2NHCH (CH(CH3) 2)C(=0)0-benzyl and R23 is CH2CH2NHCH(CH(CH3)2)C(=0)0-benzyl; 5 the compound of formula (Ila) wherein R22 is propyl and R23 is propyl; the compound of formula (Ila) vherein R22 is methyl and R23 is methyl; 10 the compound of formula (Ila) wherein R22 is cyclopropylmethyl and R23 is cyclopropylmethyl/ the compound of formula (Ila) wherein R22 is n- 15 hexyl and R23 is n-hexyl; the compound of formula (Ila) wherein R22 is n-butyl and R23 is n-butyl; 20 the compound of formula (Ila) vherein R22 is N- morpholinoethyl and R23 is N-morpholinoethyl; the compound of formula (Ila) wherein R22 is n-heptyl and R23 is n-heptyl; 25 the compound of formula (Ila) vherein R22 is CH2CH=CH(CH3)2 and R23 is CH2CH=CH(CH3)2» the compound of formula (Ila) vherein R22 is ethyl 30 and R23 is ethyl; « the compound of formula (Ila) vherein R22 is CH2CH»CH(CH3)2 and R23 is H; 22 the compound of formula (Ila) vherein R22 is 1« pentyl and R23 is i-pentyl; the compound of formula (Ila) wherein R22 ļs 4. 5 pyridylmethyl and R23 ļs 4-pyridylmethyl; the compound of formula (Ila) vherein r22 is 2-methallyl and R23 is 2-methallyl; 10 the compound of formula (Ila) vherein r22 is n- pentyl and R23 is n-pentyl; the compound of formula (Ila) vherein R^2 is i-octyl and R23 is i-octyl; 15 the compound of formula (Ila) vherein r22 is i-hexyl and R23 is i-hexyl; the compound of formula (Ila) vherein r22 is i- 20 heptyl and R23 is i-heptyl; the compound of formula (Ila) vherein R^2 is i-butyl and R23 is i-butyl; 25 the compound of formula (Ila) vherein R22 is 3- propargyl and R23 is 3-propargyl; • the compound of formula (Ila) vherein R22 is benzyl and R23 is benzyl; 30 the compound of formula (Ila) vherein R23 is 2-pyridylmethyl and R23 is 2-pyridylmethyl; the compound of formula (Ila) vherein R2^ is 35 phenylpropyl and R23 is phenylpropyl; 23 LV 10096 the compound ©f formula (Ila) vherein R22 is allyl and R23 is isoprenyl; 5 the compound of formula (Ila) vherein R22 is 1- cinnamyl and R23 is l-cinnamyl.

More specifically preferred are the follovdng 10 compounds of formula (I)* which have IC50 or Ki values of less than about 10 nM for inhibiting HIV protease: the compound of formula (Ila) vherein R22 is allyl and R23 is allyl; 15 the compound of formula (Ila) vherein R22 is propyl and R23 is propyl; the compound of formula (Ila) vherein R22 is 20 cyclopropylmethyl and R23 is cyclopropylmethyl; the compound of formula (Ila) wherein R22 is n-hexyl and R23 is n-hexyl; 25 the compound of formula (Ila) vherein R22 is n- butyl and R23 is n-butyl; the compound of formula (Ila) vherein R22 is CH2CH»CH(CH3)2 and R23 is CH2CH=CH(CH3)2; 30 the compound of formula (Ila) vherein R22 is CH2CH2CH (CH2) 2 and R23 is H; the compound of formula (Ila) vherein R22 is 2-35 methallyl and R23 is 2-methallyl; 24 the compound of formula (Ila) wherein R22 ļs n_ pentyl and R23 is n-pentyl; the compound of formula (Ila) vherein R22 ig i-hexyl and R23 is i-hexyl; the compound of formula (Ila) vherein R22 is benzyl and R23 is benzyl; the compound of formula (Ila) vherein R22 is allyl and R23 is isoprenyl; the compound of formula (Ila) vherein R22 is l-cinnamyl and R23 is l-cinnamyl.

The folloving preferred compounds of formula (I) exhibit IC90 values of less than about 10 μg/mL for the inhibition of HIV grovth: the compound of formula (Ila) vherein R22 is allyl and R23 is allyl; the compound of formula (Ila) vherein R22 is cyclopropylmethyl and R23 is cyclopropylmethyl; the compound of formula (Ila) vherein R22 is n-butyl and R23 is n-butyl; « the compound of formula (Ila) vherein R22 is CH2CH=CH(CH3)2 and R23 is CH2CH=CH (CH3)2; the compound of formula (Ila) vherein R22 is propyl and R23 is propyl; 25 LV 10096 the compound of formula (Ila) v/herein R22 is i-pentyl and R23 is i-pentyl; 5 the compound of formula (Ila) vherein R22 is benzyl and R23 is benzyl.

In the present invention it has been discovered that the compounds above are useful as inhibitors of HIV 10 protease and similar retroviral proteases, and for the treatment of HIV infection and similar retrovirus infections.

The present invention also provides methods for the treatment of HIV infection by administering to a host 15 infected with HIV a pharmaceutically effective amount of a compound of formula (I) as described above.

The compounds herein described may have asymmetric centers. Ali chiral, diastereomeric, and racemic forms 20 are included in the present invention. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and ali such stable isomers are contemplated in the present invention.

25 When any variable (for example, R1 through R28, R4A and R^A, m, n, W, Z, etc.) occurs more than one time in any constituent or in formula (I) or (II), or any other formula herein, its definition on each occurrence is independent of its definition at every other occurrence. 30 Also, combinations of substituents and/or variables are * permissible only if such combinations result in stable compounds.

As used herein, "altyl* is intended to include both branched and straight-chain saturated aliphatic 35 hydrocarbon groups having the specified number of carbon 26 atoms; *alkoxy· represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; ^cloa^l* is intended to include satura ted -ring groups, such as cyclopropyl, cyclobutyl, 5 cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl; and •biycloalkyl* is intended to include saturated bicyclic ring groups such as [3.3.0]bicyclooctane, (4.3.0]bicyclononanef I4.4.0jbicyclodecane (decalin), t2.2.2Jbicyclooctane, and so forth. "Alkenyl· is 10 intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the Chain, such as ethenyl, propenyl, and the like; and •alkynyl· is intended to include 15 hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like. *Halo· as used herein refers to fluoro, chloro, bromo, and iodo; and 20 "counterion* is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate, and the like.

As used herein, "aryl· or 'aromatic residue· is intended to mean phenyl or naphthyl; •carbocyclic· is 25 intended to mean any stable 5- to 7- membered monocyclic or bicyclic or 7- to 14-membered bicyclic or tricyclic carbon ring, any of vhich may be saturated, partially unsaturated, or aromatic, for example, indanyl or tetrahydronaphthyl (tetralin). 30 As used herein, the term •heterocycle* is intended « to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring which is either saturated or unsaturated, and vhich consists of carbon atoms and from 1 to 3 heteroatoms 35 selected from the group consisting of N, 0 and S and 27 LV 10096 vherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen may optionally be guaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is 5 fused to a benzene ring. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting 10 compound is stable. Examples of such heterocycles include, but are not limited to, pyridyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiopheny 1, indolyl, indolenyl, quinolinyl, isoquinolinyl or benzimidazolyl, 15 piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tētrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl. The term substituted*, as used herein, means that an one or more 20 hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normai valency is not exceeded, and that the substitution results in a stable compound.

By 'stable compound* or ’stable structure* is meant 25 herein a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic aģent.

As used herein, *pharmaceutically acceptable salts 30 and prodrugs* refer to derivatives of the disclosed compounds that are modified by making acid or base salts, or by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to 35 the parent compounds. Examples include, but are not 28 limited to, mineral or organic acid salts of basie residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; acetate, formate and benzoate derivatives of alcohols and amines; 5 and the like.

Pharmaceutically acceptable salts of the compounds of the invention can be.prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in 10 water or in an organic solvent, or in a mixture of the two; generally, nonagueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack 15 Publishing Company, Easton, PA, 1985, p. 1418, the disclosure of which is herefcy incorporated by reference.

Svnthesis 20 25 30

The compounds of the present invention may be synthesized using the general synthetic procedures deseribed below. Each of the references cited below are hereby incorporated herein by reference.

Compounds of the invention wherein: W is -N(R22)C(=Z)N(R23)- or -N(R22)C(=0)C(=0)N{R23)-; R5 is -OR20 or H; R6 is -OR21 or H; and n is 1; can be formed from diamines of formula (III): 35 29 LV 10096

(III) 5

The diamines of formula (III) can be synthesized as described in copending commonly assigned patent application Jadhav et al. USSN 07/714,042, filed 5/31/91. Alternative methods which can be used to 10 synthesize the compounds of structure (III) above are described in European Patent Application Publication Number 402646A1, U.S. Patent 4,837,204, and Canadian Patent Application 2,026,832 . 15 The compounds of formula (III) can be cyclized to form compounds of formula (IV) under conditions normally used to form cyclic ureas, as is known to one skilled in the art. Reaģents J-(C*Z)-J', where J and J* are leaving groups, are employed, preferably under 20 relatively dilute conditions (for example, less than about 0.1 M), to effect ring closure to provide compounds of formula (I). Many examples of J and J' are known; preferred are carbonyl diimidazole, thiocarbonyldiimidazole, phosgene, thiophosgene, 25 diphenyl carbonate, or diphenyl thiocarbonate.

Additionally, for compounds vherein W is - * N(R22)C(=0)C(*0)N(R23)-, compounds of formula (III) can be reacted with activated derivatives of oxalic acid, preferably oxalyl chloride, under the above conditions 30 to form the diamide. 30

For compounds of the invention vhere R2^ or R21 is -OH, it is advantageous to protect the free hydroxyl before cyclization. Protecting groups used can include any of those listed in Greene, protective Groups in 5 Organic Synthesis. Chapter 2, Wiley, NY (1981) . The preferred protecting groups are trimethylsilylethoxymethyl (SEM) or methoxymethyl (MOM).

Cyclization of compounds of formula (III) results 10 in structure (IV) (i.e.f structure (I) vherein W is -N{R22)C(*0)C(=0)N(R23)- and n is 1) .

Z

15 (IV)

Another, preferred method to form compounds of formula (IV), in cases vherein R22 and R23 are linked to their respective nitrogens by a CH2 residue, is to 20 cyclize a compound of structure (III) vhere R22 and R23 are hydrogen/ and to alkylate the nitrogens using a base and an alkylating aģent, using methods veli knovn in the art, The preferred base is sodium hydride, and the preferred alkylating aģents are R22Y and R23Y, vherein Y 25 is a halogen, triflate, or mesylate, preferably a bromide or iodide. Preferred conditions are in polar aprotic solvents betveen 0 and 100 eC.

Cleavage of protecting groups, if employed, yields 30 structures of formula (I) vherein R3 and R3 are hydroxyl. 31 LV 10096

When r5 and R^ are other than OR^O and OR^l, some Chemical manipulation of functional groups may need to be performed in the preparation of the compounds of 5 formula (III) or (IV), as is appreciated by one of skill in the art of organic synthesis. Described below are examples of such procedures.

Methods for obtaining compounds vrherein R^ is OH 10 and R® is OR^1 include protection of nitrogen, if necessary, followed by reaction of the diol with one equivalent of base and one equivalent of acyl halide, alkyl halide, alkoxyalkyl halide, alkoxycarbonyl halide, ben2oyl halide, diphenyl 15 carbonate or phenylisocyanate, and purification by column chromatography of the unvanted bis-alkylated and unreacted material.

Methods for obtaining compounds vherein R^ is OH 20 and R^ is H include protection of nitrogen, if necessary, and reduction of the diol to the monool using techniques known in the art (see, for example, Chem. Comm. 1971, 1097; J. Org, Chem. 1969, 3923). The preferred method is formation of 25 cyclic diol ester and reduction using hydride.

Deprotection of nitrogen, if necessary, results in the desired compound.

Methods for obtaining compounds vherein R^ is OH 30 and R® is F include protection of nitrogen, if e necessary, folloved by formation of mono-protected diol as described above. Reaction with a fluorinating aģent, preferably diethylaminosulfurtrifluoride (DAST) fReaģents.for 35. Organic Synthesis, Vol. 13, p. 110, Wiley 32

Interscience, NY, 1988), provides the alkyl fluoride. Deprotection of nitrogen, if necessary, and hydroxyl results in the desired compound.

5 Methods for obtaining compounds vherein R^ is QH and r6 is include protection of nitrogen, if necessary, and Standard conditions for oxidizing glycols to pinacols. The preferred oxidant is one equivalent of pyridinium dichromate in 10 dichloromethane, or one equivalent of NaOCl in HOAc. Deprotection of nitrogen, if necessary, results in the desired compound. Alternatively, a monohydroxy compound described above can be oxidi2ed to the ketone under Standard conditions, 15 preferably Swern oxidation using oxalyl chloride, DMSO and Et3N, folloved by alpha-hydroxylation of the ketone (see Tet. Lett. 1981, 607; Tet. Lett. 1982, 2917).

20 Methods for obtaining compounds vherein R^ is OH and R® is difluoro include protection of nitrogen, if necessary, and hydroxyl of the above obtained pinacol, folloved by reaction of the carbonyl vith a fluorinating reaģent, such as DAST. Deprotection 25 of hydroxyl and nitrogen, if necessary, results in the desired compound.

Methods for obtaining compounds vherein R^ and R® join to form an epoxide include protection of 30 nitrogen, if necessary, folloved by Standard « conditions for the formation of an epoxide from a glycol (see, for example, J. Org. Chem. 1981, 3361). Preferred is the reaction of the glycol vith more than 2 equivalents of base and one 35. eguivalent of an activating group, such as 33 LV 10096 methanesulfonyl chloride. Deprotection if necessary results in the desired compound.

Methods for obtaining compounds vherein R3 is OH 5 and R3 is C1-C3 alkyl include protection of nitrogen, if necessary, and reaction of the epoxide prepared above with C1-C3 alkylmetal reaģents. Preferred is the reaction of lithium dialkyl cuprates in aprotic solvents at low temperatures (-10 78 to -40 eC) (see Carruthers, Some Modern Methods ĪD .Orqanifi..Synthegla, p. 64, Cambridge University Press, 1978).

With a judicious selection of reaģents, as is well 15 appreciated to one skilled in the art, these manipulations can be performed in a straightforward manner to yield the claimed combinations of R3 and R®. 20 Compounds of the invention vherein: W is -N(R22)C(*Z)N(R23)“ or -N(R22)C(*0)C(*0)N(R23)“, and n is 0; 25 can be synthesized from diamines of formula (V): R5

(V) 30 34 which can in turn be synthesized as described in European Patent Application Publication Number 402 646 AI. 5 Protection, if necessary, cyclization, and functional group manipulation if desired is performed as described above to obtain compounds of structure (VI):

Z

Compounds of the invention vherein: 15 H is -0C(«0)0- and n is 1; can be formed from diols of structure (VII):

vihich can in turn be synthesized as described in copending, commonly assigned U.S. patent application 25 Jadhav et al. USSN 07/714,042, filed 5/31/91. 35 LV 10096

Functional group manipulation, if desired, may be performed as described above, folloved by cyclization to the carbonate using Standard conditions, preferably phosgene or thiophosgene in the presence of 2 equivalents of a base such as potassium hydride, to obtain compounds of structure (I).

Compounds of the invention vherein: W is -N(R22)C(=*Z)0- and n is 1; can be formed from aminoalcohol of structure (VIII):

(VIII) which can in turn be synthesized as described in a copending, commonly assigned U.S. patent application Jadhav et al. USSN 07/714,042, filed 5/31/91, by employing a single equivalent of azide in the reaction of the diol of formula (VII) to obtain the azidoalcohol, folloved by reduction as described in USSN 07/714,042, to form the aminoalcohol. *

Protection, if necessary, and functional group manipulation, if desired, is performed as described above, folloved by cyclization to the carbamate using Standard conditions, preferably phosgene or thiophosgene 36 in the presence of 2 equivalents of a base, such as potassium hydride, to obtain compounds of structure (I). 5 Compounds of the invention wherein: W is -0C(=Z)0- and n is 0; can be formed from the diol of structure (IX): 10

R5 (IX) 15 which can in turn be synthesized by the reaction of R^CHO with the lithium anion of 1,3 dithiane, folloved by the reaction. of R7CHO with the anion of the product (see Carruthers, Some Modern Methods in Organic Synthesisf p. 45, Cambridge University Press, 1978). 20 Cleavage of the dithiane with mercuric ion yields the acyclic alpha, alpha’ dihydroxyketone.

Functional group manipulation, if desired, is performed as described above, folloved by cyclization to 25 the carbonate using Standard conditions, preferably phosgene or thiophosgene, in the presence of 2 equivalents of a base such as potassium hydride, to obtain compounds of structure (I).

Compounds of the invention vherein: 30 5 37 LV 10096 W is -N(R22)C(=Z)0- and n is 0 can be formed from aminoalcohol of structure (X): R5 R22HN R4i

R4 R7 (X) 10 which can in turn be synthesized by the techniques described in European Patent Application Publication Number 402 646 AI for the synthesis of compounds of structure (V), above; however, in place of azide, in opening the oxirane (shown below), an oxygen 15 nucleophile, such as acetate or hydroxide ion, is reacted in the presence of a polar aprotic solvent, such as DMSO.

20

Alternatively, the oxirane is treated with a catalytic amount of a strong acid in water and a cosolvent, if necessary, which technique also removes the BOC protecting group.

Protection, if necessary, and functional group manipulation, if desired, is performed as described 25 38 above, folloved by cyclization to the carbamate using Standard conditions, preferably phosgene or thiophosgene in the presence of 2 equivalents of a base such as potassium hydride, to obtain compounds of structure (I).

Compounds of the present invention wherein: W is -C(R25) (R26)N(CH3) (O)C(R27) (R28)-; can be synthesized from aminOalcohols (VIII) and (X) by the following steps: protection of nitrogen, if necessary, preferably with a benzyloxycarbonyl group; activation of the alcohol to displacement, preferably with a sulfonate derivative, such as mesyl chloride; removal of the nitrogen protecting group, preferably with hydrogen in the presence of a catalyst, such as palladium on carbon; and heating under dilute conditions in the presence of a base such as triethylamine to effect cyclization.

The secondary cyclic amine is then methylated, preferably with formic acid/formaldehyde, and oxidized, preferably with a peracid, such as MCPBA, to form compounds of formula (I), vherein W is -C(R25) (R26)N(CH3) (O)C(R27) (R28)-. The secondary cyclic amine can alternatively be directly oxidized to form structure (I), where W is -C(R25) (R26)N(OR28)C(R27) (R28)-.

Compounds vherein: W is -C{R25) (r26)C(,z)C(r27) (r28)_ and n is 0; 39 LV 10096 can be prepared by the alkylation of protected cyclohexanedione (XI) with the required R4-LG and R7-LG, and optionally R4A-LG and R?A-LG groups, vherein LG represents a leaving group such as halogen or sulfonate 5 ester.

(XI) 10

Reduction of the ketone to the alcohol, preferably with LiAlH4, or manipulation to other values of R® as described above, is folloved by cleavage of the ketal (see Greene, ProtectĪve.Group-S in Organie Synthesis. 15 Chapter 2, Wiley, NY, 1981) . Protection of the alcohol or other reactive groups, folloved by alkylation ketone and deprotection, provides compounds of structure (I), vherein W is -C(R25) (r26)C(=Z)C(R27) <r28)> and n is 0. 20

Compounds vherein: W is -C(r25) (r26)C(»Z)C(R27) (r28)_ and n ļs i; 25 40 can be prepared frora the protected hydroxyketones described immediately above by ring expansion, for example via the Tiffeneau-Demyanov reaction (March, Advanced Orpanlc Chemistry. p. 965, Wiley, NY, 1985), or 5 by treatment with dimethylsulfonium ylide to form the spiro-epoxide, folloved by acid-cataly2ed ring expansion to the cycloheptanone (ibid., pp. 871, 966).

The above routes have the advantage of producing a 10 number of stereoiomers which, upon purification, can be evaluated for the best combination of potency, safety and in vivo availability. 15 Compounds vherein: W is -C(R25) (R26)C(F2)C(R27) (R28)- and n is 0 or 1; 20 can be obtained from the above-described protected hydroxyketone by treatment with a fluorinating reaģent, preferably DAST, as described above. 25 Compounds vherein: W is -N(R22)C(=*2)C(R27) (R28)- and n is 0; can be obtained by cyclization of compound (XII) to the 30 lactam using techniques known in the art (March, «

Advanced Oroanic Chemistryf p. 371, Wiley, NY, 1985). 41 LV 10096

OP h2n R27 '

,OH (XII) 5

Compounds of structure (XII) can in turn be obtained as described in European Patent Application Publication Number 434 365 A2, European Patent Application Publication Number 386 611 A2, European 10 Patent Application Publication Number 389 127 Al, and CA 2005337, each of which are hereby incorporated by reference. OP in structure (XII) designates protected oxygen. Hydroxyl can be protected by the use of any of a number of groups as described in Greene, Protective 15 Grouos in Organic Svnthesis, Chapter 2, Wiley, NY (1981).

If desired, the resulting lactam (XIII):

O 20

OP (XIII) 42 can be further functionalized, for example by the following techniques: the lactam nitrogen can be alkylated with an R22-LG group, preferably employing sodium hydride in DMF; an R4A, R7 or R7a group can be 5 added by deprotection and oxidation of the alcohol, followed by alkylation of the enolate using R4a-LG, R7-LG or R7a-LG; and reduction of the ketone to hydroxyl or othervise functionalizing to obtain the R8 group of choice as described above. 10

Compounds vherein: W is -N(R22)C(=Z)C(R27) (R28) - and n is 1; 15 can be obtained through techniques knovn in the art from ketones of structure (I) vherein W is -C(R28) (R28)C(=Z)C(R27) (R28) - and n is 0, preferably via the Beckmann rearrangement (March, Advanced Orcanic 20 Chemistrv. p. 987, Wiley, NY, 1985). Manipulation of the R8 group, if desired, as described above provides R8 and R8-substituted examples of (I), vherein W = -N(R22)C(=z)C(R27)(R28)- and η * 1. 25 Compounds vherein: W is -C(R25){R26)C(=Z)0- and n is 0 or 1; can be obtained from compounds of structure (I), vherein 30 W = -N(R22)C(=Z)C(R27) (R28)-, n * 0 or 1, and R22 = H, for example, by hydrolysis of the lactam, folloved by displacement of the primary amine by hydroxyl, and closure to the lactone (March, Advanced Orcanic Chemistrv. p. 348, Wiley, NY, 1985). 35 43 LV 10096

Similarly, compounds vherein: W is -C(R25)(R26)C(=Z)S- and n is 0 or 1; can be obtained from compounds of structure (I), wherein W = -N(R22)C(=Z)C(R27) (R2^)-, n * 0 or 1, and R22 = H, for example, by hydrolysis of the lactam, followed fcy conversion of the primary amine to the diazonium salt, displacement by NaSH, and closure to the thiolactone (March, Advanced .Organic Chemistrv. p. 601, wiley, NY, 1985).

Compounds of structure (I) described above vherein z = 0 can be converted to the thio derivatives, Z = S, using Standard conditions (March, Advanced Organic Chemistrv, p. 792, Wiley, NY, 1985); preferred is the use of the disulfide described in Buli. Soc. Chim.

Efiļgea 1978, 223.

Structures (I) described above wherein z * 0 can be converted to the imino derivatives, Z = NR2^, using Standard conditions. When R24 is OH or 0-alkyl, the oximes can be formed and alkylated if desired as described in March, Advanced Organic Chemistrv., pp. 359, 805, wiley, NY, 1985. The hydrazones and imines can be formed similarly (iliid, pp. 533, 797).

It is expected that the compounds of the invention can also be prepared as shown in Scheme 1 (shown below). The intra-molecular coupling of the N-substituted or * unsubstituted dialdehydes may be achieved by organometal reaģents derived from vanadium, titanium, samarium etc. The dialdehyde precursors can be prepared from the commercially available materiāls by the methods known to those skilled in the art of organic synthesis, preferably by the technigues 44 disclosed in copending commmonly assigned U.S. Patent Application, Hodge, USSN 07/659,442, filed 2/21/91.

Compounds wherein w is -N(r22)c(=o)N(r23)- and n is 5 2 can be synthesized as shown in Scheme 2 (below). The eight-membered cyclic urea in Scheme 2 can be protected, if necessary, and manipulated as described above to yield the desired compounds. 10

The synthesis of compounds of the invention is described in further dētai1 below.

Procedure 1 15

Preparation of di-N-CBZ protected l,4-diamino-2,3-diols (XIX):

ZN NZ

20 (XIX)

Detailed experimental procedures for the synthesis of compound (XIX) are described in copending commonly assigned patent application Jadhav et al. USSN 25 07/714,042, filed 5/31/91.

Procedure.2

Preparation of di-0 protected di-N-CBZ lf4-diamino diols 30 (XXa) and (XXb): 45 LV 10096

ZN NZ

(XXa) R=SEM

(XXb) R=MOM 5 A. Protection as 2-(trimethylsilyl) ethoxy methyl (SEM) ether (XXa) .·

Compound (XIX) (60 g, .105 mmol) was dissolved in 10 dry dimethoxyethane (600 mL). Diisopropylethylamine (75 mL) and SEMCl (66.8 g, 400mmol) were added and the mixture stirred for 16 h at room temperature under N2.

The solution was diluted with water (1L) and extracted with hexane (400mL). The organic layer was separated and 15 washed with water (2xl00mL). The aqueous layers were combined and extracted with hexane (2x300mL). The organic layers were combined, washed with water (2xl00mL), dried over MgSO*, filtered and evaporated. The residue was chromatographed on S1O2 and eluted with 10- 20 30% ethyl acetate/hexane to afford a white solid (91g, 100%). NMR(CDCl3) :δ 7.0-7.4 (m, 20H, Ph), 5,01 (br s, 4H, PhCH2CO), 4.5-4.95 (m, 6H, NH, OCH20), 3.6-4.25 (m, 4H, CHOCH2, CJiNH), 3.5 (s, 4H, OCH2CH2), 2.76 (br d, 4H, PhCH2), 0.8-1.0 (m, 4H, S1CH2). MS: 846 (M+NH4, 100), 25 695 (M-SEM, 40). B. Protection as methoxymethyl (MOM) ether (XXb). 4

Compound (XIX) (.50 g, 0.88 mmol) was dissolved in 30 dry DMF (lOmL). Diisopropylethylamine (.46 mL, 2.64 mmol) and methoxymethyl bromide (.165 mL, 2.02 mmol) were added and the solution stirred at 40 °C under. nitrogen for four h. TLC (50/50 ethyl acetate /methylene 46 chloride) showed that the reaction was cpmplete. The roixture was partitioned betveen methylene chloride (50 jhL) and 5% HCl (30 mL). The organic layer was separated , washed with water (5x20 mL), brine (20 mL), dried over 5 MgSO*, filtered and evaporated to a light yellow oil. Chromatography on S1O2 and elution with 1-20% ethyl acetate/methylene chloride afforded (xxb) as a clear oil ( .29 g, 53%). NMR (CDCI3): δ 6.95-7.42 (m, 20H, Ph), 5.1-3.8 (mf 10 complex), 3.35 (s, 6H, OCH3), 2.8-2.95 <m, 4H, PhCH2). MS: 657 (13/ M+l), 674 (21, M+NH4), 522 (84), 414 (100), 370 (34).

Procedure 3 15

Deprotection of amines (XXa) and (xxb) via hydrogenation to af ford (XXla) and (XXIb): NH2 NHj

(xxia) R=SEM (XXIb) R=MOM 20 A. Hydrogenation of SEM ether (XXa). 25

Compound (XXa) (90 g, 108.5 mmol) was dissolved in absolute ethanol (2.5 L). 5% Pd/C (6.5 g) was added and 4 the solution was stirred under hydrogen for 1.5 h until hydrogen uptake ceased. TLC (20/80 ethyl acetate/hexane) 30 showed that the reaction was complete. The solution was filtered through celite and evaporated at reduced pressure to a colorless gum (60 g, 99%). NMR (CDCI3): 5 7.1-7.35 (m, 10H, Ph), 4.72 (br d, 4H, 0CH20), 3.5-3.9 47 LV 10096 (m, 6H, NH2, CHOCH2), 3.15 (m, 2h, CHNH2), 2.55-2.95 (m, 4H, PhCH2), 0.95 (m, 4H, S1CH2). - B. Hydrogenation of MOM ether (XXb). 5

Compound (XXb) (.29 g, .441 mmol) was dissolved in ethyl acetate (6 mL) and methanol (3 mL). 10% Pd/C (70 mg) was added and the solution stirred under hydrogen until H2 uptake ceased. TLC (20/80 methanol/ethyl 10 acetate) showed that the reaction was complete. The solution was filtered through Celite and evaporated at uced pressure to afford 3b as a clear oil (.132 g, 77.4%). NMR (CDCI3): 5 7.1-7.35 ( m, 10H, Ph), 4.58 (s( 4H, OCH2O), 3.75 (br s, 2H, CŪOCH2), 3.3-3.5 (m, 2H, 15 CūNH2), 3.23 (s, 6H, OCH3), 2.85 (br d, 4H, PhCH2). MS: 389 (M+l, 100), 345 (3.7), 280 (1.8), 120 (6.1).

Procedure .4 20

Formation of cyclic ureas (xxila) and (XXIIb): 25

O

HN

R=SEM R=MOM A. Cyclization of SEM ether (XXIa).

Compound (XXla) (40 g, 71.3 mmol) was dissolved in 30 methylene chloride (200 mL). Carbonyl diimidazole (13.87 g, 85.6 mmol) was dissolved in methylene chloride (200 48 mL) in a separate flask. Each solution was then pumped into dry methylene chloride (6 L) at a rāte of 90 mL/h. The mixture was then stirred for 18h at room temperature under nitrogen. TLC (60/40 ethyl acetate/hexane) showed the reaction was complete. The solvent was removed at reduced pressure and residue chromatographed on S1O2 and eluted with 1-501 ethyl.acetate/hexane to afford (XXlla) as a white solid (38.82g, 93%). mp: 75-76°C. NMR (CDCI3): 67.05-7.4 (m, 10H, Ph), 4.6-4.8 (dd, 4H, OCH20), 4.08 (s, 2H, CHOCH2), 3.5-3.91 (m, 8H, NH, CtfNH, OCH2CH2), 2.86. (br d, 4H, PhCH2), 0.8-0.95 (m, 4H, SiCH2). MS: 587 (M+l, 100). B. Cyclization of MOM ether (xxib). «

Compound (XXIb) (.53 g, 1.364 mmol) was dissolved in dry methylene chloride (20 mL). In a separate flask, carbonyl diimidazole (.265 g, 1.64 mmol) was dissolved in methylene chloride (20 mL). To a third flask containing pyridine (.22 mL, 2.73 mmol) in methylene chloride (100 mL) at room temperature under nitrogen were added the first two Solutions via syringe pump at a rāte of 1.7 mL/h. The solution was stirred overnight at room temperature. TLC (50/50 ethyl acetate/methylene chloride) showed that the reaction was complete. The solution was washed with 5% HCl (50 mL), NaHC03 (50 mL), brine (50 mL), dried over MgSC>4, filtered and evaporated. The residue was chromatographed on Si02 and eluted with 50-75% ethyl acetate/methylene chloride to afford (xxilb) as a colorless gum (198 mg, 35%). NMR < (CDCI3):δ 7.1-7.4 (m, 10H, Ph), 4.65 (q, 4H, OCH20). 4.13 (s, 2H, NH), 3.89 (t, 2H, CJJNH), 3.59 (s, 2H, CHOCH2), 3.18 (s, 6H, OCH3), 2.87 (m, 4H, PhCH2). MS: 415 (M+l, 100), 102 (11). 49 LV 10096

Procedurfi-S

General alkylation/hydrolysis procedure: 5 Compound (XXlla) (1 mmol) in dry DMF (5 mL) was added to a flask containing sodium hydride (10 mmol, that had been vashed with hexane, 3x20 mL) in DMF (5 mL). The solution vas stirred at room temperature under nitrogen for 5 min. Evolution of hydrogen gas was 10 observed. The appropriate alkyl bromide (5 mmol) was added and the solution was stirred at room temperature under nitrogen for lh. Hindered alkyl bromides required heating at 40-70 °C for up to 5 h. TLC (40/60 ethyl acetate/hexane) was used to ensure that no starting 15 material remained. The solution was quenched with methanol (1 mL), partitioned between ether (60 mL) and water (50 mL) and the organic layer was removed. The agueous layer was washed with ether (50 mL), the organic layers combined and washed with vater (4x30 mL), brine 20 (30 mL), dried over MgSOi, filtered and evaporated. In cases where the alkyl bromide contained nitrogen, 1 N NaOH was used in place of vater.

The crude product vas hydrolyzed directly in methanol (10 mL) and 4 N HCl/dioxane (5 mL) for up to 16 25 h at room temperature. The solution was evaporated and chromatographed directly on S1O2 to afford the bis-alkylated cyclic ureas. where nitrogen was present, the Solutions vere first basified with 1 N NaOH and extracted vith ethyl acetate, dried over MgSOi, 30 filtered, evaporated and chromatographed.

Hydrolysis of (XXIlb) under the same conditions gavē 67% yield of the Ν,Ν-unsubstituted cyclic urea Example 1A, mp 170-174 °C.

Example. 1G 35 50

The experimental procedure is similar to the synthesis of Example 1E. The isomer, (2R,3R,4R,5R)-2,5-5 diamino-1,6-diphenyl-3,4-hexanediol, needed for the synthe$is was isolated from the vanadium trichloride coupling reaction, as described in copending commonly assigned patent application Jadhav et al. USSN 07/714,042, filed 5/31/91 (see Procedure 1 above). 10 Example 1G: 13C NMR (CDC13) : (75.48 MHz) 37.387, 51.51, 65.136, 72.779, 118.649, 126.540, 128.409, 129.714, 134.618, 137.757, 162.705.

Example 1F

Compound (XXIIb) (0.85g) was heated with mixture of acetic acid (9.5 mL) and water (0.5 mL) at 85 °C for 4h. 20 After extraction with dichloromethane, folloved by vashing the organic extract with saturated sodiumbicarbonate and brine, a mixture was provlded which, on separation by column chromatography, furnished (XXIIb) (TLC 1:10 ethyl acetate/hexane Rf - 0.4/ 0.54g), the desired mono-alcohol 51 LV 10096 intermediate ( TLC 1:10 ethyl.acetate/hexane Rf * 0.1; 0.13g), and overhydrolysed diol (0.05g) .

The above mono-alcohol intermediate 0.25g (0.466 mmol), triphenylphosphine 183mg (0.7 mmol), diethylazadicarboxyalte 0.11 mL (0.7 mmol), and chloroacetic acid 66mg (0.7 mmol) were stirred in 5 mL anhydrous tetrahydrofuran at 0 °C for 15 minūtes and then at room temperature for 18h. The excess reaģents were quenched with 0.5 mL methanol and the mixture allowed to stir for 20 minūtes. The mixture was purified by silica gel column chromatography to provide the desired chloroacetate intermediate with inversion of configuration. 13C NMR (CDC13) : (75.48 MHz) -1.373, 14.413, 14.487, 18.253, 25.591, 33.851, 35.741, 40.505, 48.824, 49.962, 57.507, 58.234, 66.589, 67.885,73.179, 77.423, 95.454, 117.296, 118.554, 126.588, 126.887, 128.518, 128.610, 129.117, 129.199, 129.479, 133.686, 134.168, 136.324, 138.285, 155.698, 166.323.

The above chloroacetate intermediate 73mg (0.12 mmol) in 2mL dry methanol was treated with 0.25 mL (0.5M) sodium methoxide and stirred for 30 minūtes at room temperature.

The contents were then treated with 0.3 mL (4% HC1 in methanol) and stirred for 4.5h at room temperature. The residue after removal of solvent was purified on silica gel column to provide Example 1F.

Example 1F: 13C NMR (CDC13): (75.48 MHz) 34.075, 37.672, 48.941, 48.985, 58.071, 60.640, 65.861, 73.212, 177.975, 118.669, 126.535, 126.858, 128.603, 128.815, 129.225, 133.605, 134.172, 137.637, 138.273, 155.497. „

Examples 1A-12. ΙΆΑ-lĀZ. and 1BA-1BD 5 52

The compounds listed in Table la (Examples 1A-1Z, 1AA-1AZ, and 1BA-1BD) were synthesized ušing the above-described procedures.

Xab.lfc.-la

Exarcpls Nuiribsi Stereo^ iA&m&s (2.3,4,.51 E22 £23 Ki 1A RSSR H H ♦ 1B SRRS H H + 1C RSSR CH2CH=CH2 CH2CH=CH2 + ♦ + ĪD SRRS CH2CH=CH2 CH2CH=CH2 ♦ - 1E SSSS H H ♦ 1F RRSR CH2CH=CH2 CH2CH=CH2 1G RRRR CH2CH=CH2 CH2CHsCH2 ++ 1H SSSS CH2CH=CH2 CH2CH=CH2 + 11 SRRS CH2Ph CH2Ph ♦ 1J SRRS (CH2)20(CH2)20Me (CH2)20(CH2)20Me + IK SRRS l-geranyl l-geranyl ♦ 1L SRRS CH2CH2OH CK2CH2NHCH(CH(CH3) 2) -C(=0)0-benzyl ♦ 1M SRRS CH2CH2(CH2CH2O)2OCH3 CH2CH2(CH2CH2O)2OCH3 + 1N SRRS 3,7-dimethyl-l-octyl 3.7-dimethyl-l-octyl ++ 10 RSSR CH3OCH2CH2OCH2CH2 CH3OCH2CH2OCH2CH2 + 1P RSSR 3,7-diaethyl-l-octyl 3,7-diaethyl-l-octyl +*> 1Q RSSR 3,7-diaethyl-l-octyl H ++ IR RSSR CH3(OCH2CH2)3 H + 53 LV 10096 1S RSSR CH3(OCH2CH2)3 CH3(OCH2CH2)3 IT RSSR HOCH2CH2 CH2CH2NHCH(CH(CH3)2) ++ -C(»0)0-benzyl 1U SRRS CH2CH2NHCH{CH{CH3)2) CH2CH2NHCH(CH{CH3)2) + -C(*0)0-benzyl -C(-0)0-b«nzyl IV RSSR propyl propyl +++ 1W RSSR methyl methyl + IX RSSR cyclopropyl-methyl cyclopropyl-methyl +++ 1Y RSSR n-hexyl n-hexyl +++ IZ RSSR n-butyl n-butyl +++ Ιλλ RSSR N-morpholinoethyl N-morpholinoethyl + 1AB RSSR n-heptyl n-heptyl ++ 1AC RSSR CH2CH-C(CH3)2 CH2CH-C(CH3)2 +++ 1AD RSSR ethyl ethyl ++ 1AE RSSR CH2CH-C(CH3)2 H +++ 1AF RSSR propyl propyl +++ 1AG RSSR CH3 CH3 + 1AH RSSR i-pentyl i-pentyl +++ 1AI RSSR 4-pyridylmethyl 4-pyridylmethyl ++ 1AJ RSSR 2-methallyl 2-methallyl +++ 1AK RSSR n-pentyl n-pentyl +++ 1AL RSSR i-octyl i-octyl ++ 1AM RSSR i-hexyl i-hexyl +++ 1AN RSSR i-heptyl i-heptyl ++ 1AO RSSR i-butyl i-butyl ++ 1AP RSSR 3-propargyl 3-propargyl ++ 1AQ RSSR benzyl benzyl +++ 1AR RSSR 2-pyridylmethyl 2-pyridylmethyl ++ 1AS RSSR phenylpropyl phenylpropyl ++ 1AT RSSR allyl isoprenyl +++ « 1AU RSSR l-cinnamyl l-cinnamyl +++ 1AV methyl cyclopropyl-methyl 1AW allyl cyclopropyl-methyl 1ΑΧ CH2CH2N(CH2)2 allyl 1ΑΥ methyl benzyl 54 1ΑΖ

1BA

N-pyrrolylethyl HO H

2-furylmethyl CH2CH2OCH(CH2)2 isoprenyl

N-pyrrolylethyl HO H

2-furylmethyl CH2CH2OCH(CH2)2

1BB 1BC methyl

1BD

The Ki values in Table 1 were determined using the assay conditions described below under HIV Protease Inhlbtion Assay. The Ki values are indicated as 5 follovs: +++ - <10 nM; ++ - 10 nM to 1 μΜ; + - >1 μΜ.

Listed below are physical data for representative compounds of the invention. 10 Example 1W: mp 170-174 °C (67% yield). MS: 355 (M+l, 100). NMR (CDCI3)δ 7.1-7.35(m, 10H, Ph), 4.03 (s,2H,CfiOH), 3.5(d, 2H, NCH), 2.8-3.1(m, 6H, PhCH2, OH), 2.58(s, 6H, NH3).

15 Example 1AD: mp 214-215 °C. MS: 383(M+1# 100). NMR (CDCI3)δ 7.1-7.35 (m, 10H, Ph), 3.95 (s, 2H, CHOH), 3.5 (d, 2H, NCH), 2.8-3.1 (m, 4H, PhCH2, OH), 2.7 (br s, 2H, . OH), 2.3 (m,2H, NCH), .95<t, 6H, CH3) . 20 Example 1AF: mp 180-182 °C. MS: 411 (M+l, 100). NMR (CDCl3)5 7.05-7.3(m, 10H, Ph), 4.0(s, 2H, CHOH), 3.68(m,2H, NCH2), 3.52(d, 2H, NCH), 3.05 (m, 4H, PhCH2), 2.1(m, 2H, NCH2), 1.6 (s, 2H, OH), 1.4 (m, 4H, MeCH2), . .79(t, 6H, CH3).

Example IZ: HRMS: Calc. 439.2960. Found: 439.2959. 25 55 LV 10096

Example 1AK: mp 125-12.7 °C. MS: 467 <M+1, 100). NMR(CDCI3)δ 7.15-7.35(m, 10H, Ph), 3.95(s, 2H, CHOH), 3.68(m, 2H, NCH2) ,3.55(d, 2H, NCH), 2.9-3.15(m, 4H, PhCH2), 2.75 (S, 2H, OH), 2.18 (m, 2H, NCH2), >8-1.45(m, 5 complex, pentyl).

Example 1Y: rop 110-112 °C. MS: 495(M+l,100). NMR(CDC13)6 7.1- 7.35 (m, 10H, Ph), 4.0(s, 2H, CHOH), 3.65 (m, 2H, NCH-H), 3.52(d, 2H, NCH), 2.8-3.2(m,4H,PhCH2), 2.15{m,2H, 10 OH), .9-1.45(m, 11H, hexyl) .

Example 1AB: mp 100-101 °C. MS: 523 (M+l,100) . NMR(CDC13)8 7.1- 7.35(m, 10H, Ph), 3.95(s, 2H, CHOH), 3.65(m, 2H, NCH-H), 3.5(d, 2H, NCH), 2.9-3.1 (m, 4H, PhCH2), 2.6{s, 15 2H, OH), 2.15(m, 2H, NCH), .8-1.4 (m, complex, heptyl).

Example II: MS: 507(M+l,100). NMR(CDC13)5 7.05-7.4(m, 20H, Ph), 4.91(d, 4H, PhCH2N), 3.5-3.65(m, 4H, NCH, CHOH), 3.05(m, 4H, PhCH2), 2.35( br s, 2H, OH). 20

Example 5i (R^2 and R^3 * allyl; R^0 and r21 « C(-0)CH3): mp. 164-166 °C. MS: 407 (M+l, 100) . NMR(CDC13)6 7.1- 7.4 (m, 10H, Ph), 5.65(m, 2H, CH2CH), 5.01 (m, 4H, CH^CH), 4.26(m, 4H, NCH2), 3.91 (s, 2H, CHOH), 3.59<d, 25 2H, CHN), 3.l(m, 4H, PhCH2), 2.7(m, 2H, CHCfli), 2.41(s, 2H, OH).

Example 1AO: MS 439(M+l,100). NMR(CDC13)5 7.15-7.35(m, 10H, Ph), 4.05(S, 2H, CHOH), 3.7(m,2H, NCH2), 3.55(d, 30 2H, NCH), 3.0-3.2(m, 4H, PhCH2), 2.65(s, 2H, OH), 1.78(m, 2H, NCH), 1.6(s, 2H, CH2CH), .82(d, 12H, CHM£2) .

Example 1AH: mp 194-195 °C. MS: 467(M+l,100) . NMR(CDC13)6 7.15-7.35(m, 10H, Ph), 3.95(s, 2H, CHOH), 3.65(m, 2H, NCH), 3.49(d, 2H, NCH), 2.9-3.1(m, 4H, PhCH2), 2.61(s, 35 56 2Η, OH), 2.2(m, 2Η, NCH), 1.1-1.5(m, complex), .9(m, 12H, CHMfi2).

Example 1AM: mp 120-122 °C. MS: 495 (M+l, 100) . NMR(CDC13)6 7.1- 7.35(m, 10H, Ph), 3.95(S, 2H, NCH), 3.45-3.7(m, 4H, NCH2, NCH), 2.9-3.2(m, 4H, PhCH2), 2.1 (m, 2H, NCH2), .78-1.45 (m, complex, hexyl).

Example 1AN: inp 105-107 °C. MS: 523(M+l, 100) . NMR(CDC13)6 7.18-7.31 (m, 10H, Ph), 3.95(s, 2H, CHOH), 3.7 (m, 2H, NCH2), 3.56(d, 2H, NCH), 2.9-3.15(m, 4H, PhCH2), 2.18(m, 2H, NCH2), .9-1.45(m, complex, hexyl).

Example 1AL: mp 144-145 °C. MS: 551 (M+l, 100) . NMR(CDC13)5 7.15- 7.35 (m, 10H, Ph), 3.95(s, 2H, CHOH), 3.65(m, 2H, NCH2), 3.55(d, 2H, NCH), 2.9-3.15(ro, 6H, PhCH2, OH), 2.15(m, 2H, NCH2), .9-1.5(m, complex, heptyl).

Example 1AC: mp 160-163 <>C. MS: 463 (M+l, 100) . NMR(CDC13)5 7.15- 7.35(m, 10H, Ph), 5.06(br t, 2H, NCH2CH), 4.1(dd, 2H, NCH2), 3.9(s, 2H, CHOH), 3.5(d, 2H, NCH), 2.8-3.1{m, 4H, PhCH2), 1.65(s, 6H, CHCI^), 1.38(s, 6H, CHCH3).

Example 1AJ: mp 205-207 °C. MS: 435(M+l, 100) . NMR(CDC13)5 7.1- 7.35(m, 10H, Ph), 4.85(s, 2H, C=CH), 4.58(s, 2H, C*CH), 4.28(d, 2H, NCH2), 3.95(s, 2H, CHOH), 3.7 (br d, 2H, CHOH), 2.9-3.2 (m, 4H, PhCH2), 2.5(d, 2H, NCH2), 1.75 (s, 6H, CH3).

Exarople 1AI: MS: 509(M+l,100). NMR(CDC13)5 7.0-8.4(m, 18H, Ph, pyr.), 4.8-5.0(m, 4H, NCH2), 3.7(s, 2H, CHOH), 3.5(d, 2H, NCH), 2.9-3.2(m, 8H, PhCH2, pyrCH2).

Example 1AP: mp 198-200 °C. MS: 403 (M+l, 100) . NMR(CDC13)8 7.2- 7.35(m, 10H, Ph), 4.5(s, 2H, CCH), 4.42(s, 2H, NCH), 57 LV 10096 4.1(s. 2H, CHOH), 3.8(d; 2H, NCH), 2.9-3.2(m, 4H,

PhCH2), 2.7-2.85(m, 4H, NCH2).

Example 10: mp 105-106 °C. MS: 531(M+l,100). NMR(CDCl3)6 7.1-7.35(m, 10H, Ph), 3.0-4.15(m, complex), 2.25(m, 2H, OH).

Example 1S: HS: 619(M+l,100). NMR(CDCl3)5 7.18-7.3 (m, 10H, Ph), 3.0-4.2(m, complex), 2.25(m,2H,OH).

Example 1P: mp 80-82 °C. MS: 607(M+l,100), 257(9.6). NMR(CDC13)6 7.05-7.35(m,10H, Ph), 3.95(S, 2H, CHOH), 3.4- 3.75(m, 4H, NCH, NCH2), 2.9-3.15(m, 4H, PhCH2), 2.1(m,2H, OH), .85-1.6(m, complex).

Example 1AA: mp 70-75 °C. MS: 553(M+l,100). NMR(CDCl3)5 7.05- 7.4(m, 10H, Ph), 3.4-4.25(m, complex), 2.9-3.15(m, 4H, PhCH2), 2.2-2.8(m, complex).

Example IX: mp 210-212 ©c. MS: 435(M+l,100). NMR(CDCl3)6 7.18-7.35(m, 10H, Ph), 4.06(s, 2H, CHOH), 3.68(brd, 2H, NCH), 3.55 (q, 2H, NCHCļJ), 3.1(m, 4H, PhCH2), 2.55 (s, 2H, OH), 2.05(q, 2H, CHCH), .9(m, 2H, NCH2CH), .42(m, 4H, -CH2-), .008(m, 4H, -CH2-).

Humbsr MS (M+l, 100%) 1B 327.9 ĪD 406.5 1H 407 1J 531 IK 463 1L 604.5 1M 619 1N 607 5 58 10 15

10 467 IR 473 IT 604 1U 793 IV 411 1AE 395 1AG 355 . 1AS 563 1AT 435 1BD 409 1AQ 507.26 1AU 559.29 Example 1AR: mp 85-87 1 °C. Example 1C: mp 164-166 °C Example 1A: mp 170-174 °C

Using the above-described techniques or variations thereon appreciated by those of skill in the art of 20 Chemical synthesis, the compounds of Tables lb can be prepared. lableJLh R“\ /p 'ir ^N'

R7

Exampls Z21 ZH ZA Zl

Mumbex 25 59 LV 10096 1ΒΕ methyl phenylmethyl 4-F- 4-F- pbenylmethyl phenylmethyl 1BF allyl cyclopropyl- 4-F- 4-F- - methyl phenylmethyl phenylmethyl 1BG allyl cyclopropyl- 4-Cl- 4-Cl- methyl phenylmethyl phenylmethyl 1BH allyl cyclopropyl- l-pyrolyl- l-pyrolyl- wethyl methyl methyl 1BI allyl ethyl 4-F- 4-F- phenylmethyl phenylmethyl 1BJ isoprenyl isoprenyl l-pyrrolyl- l-pyrrolyl- methyl methyl 1BK n-butyl n-butyl 4-hydroxy- 4-hydroxy- benzyl benzyl 1BL N-2- cyclopropyl- benzyl l-pyrazolyl- acetoamido-3- methyl inethyl methyl-butane IBM benzyl cyclopropyl- benzyl l-pyrazolyl- inethyl methyl 1BN cyclopropyl- cyclopropyl- 4-phenyl- l-pyrrolyl- methyl methyl benzyl methyl 1B0 cyclopropyl- cyclopropyl- benzyl l-imidazolyl- methyl methyl methyl IBP cyclopropyl- cyclopropyl- benzyl l-pyrrolyl- methyl methyl methyl 1BQ n-butyl cyclopropyl- benzyl l-pyrrolyl- methyl methyl 1BR cyclopropyl- cyclopropyl- benzyl l-pyrazolyl- methyl methyl methyl IBS cyclopropyl- l-pyrrolyl- l-pyrrol.\^l- methyl methyl methyl 1BT allyl allyl benzyl 4-pyridinyl- methyl 1BU N-butyl cyclopropyl- benzyl 4-pyridinyl- methyl inethyl 60

Using the above-described techniques or variations thereon appreciated by those of skill in the art of Chemical synthesis, the compounds of Tables 3-13 (shown 5 below) can also be prepared.

Utilitv

The compounds of formula (I) possess retroviral 10 ' protease inhibitory activity and are therefore useful as antiviral aģents for the treatment of virai diseases. More particularly, the compounds of formula (I) possess HIV protease inhibitory activity and are effective as inhibitors of HIV growth. The protease inhibitory 15 activity of the compounds of the preserft invention is demonstrated using Standard assays of protease activity, for example, using the assay described below for assaying inhibitors of HIV protease activity. The ability of the compounds of the present invention to 20 inhibit virai growth or infectivity is demonstrated in Standard assay of virai grovth or infectivity, for example, using the assays described below. A compound is considered to be active if it has an IC50 or Ki value of less than about 1 mM for the 25 inhibition of HIV protease or HIV virai growth or infectivity. HIV Protease Inhibition Assay

Materials:

Protease: Inclusion bodies of E. coli harboring plasmid containing HIV protease under the control of an 30 61 LV 10096 inducible T7 promoter were prepared according to Cheng et. al (1990) Gene 87: 243 . Inclusion bodies were solubilized in 8 M urea, 50 mM tris pH 8.0. Protease activity was recovered by dilution 20-fold into buffer containing 50 mM sodium acetate pH 5.5, 1 mM EDTA, 10% glycerol and 5% ethylene glycol. Enzyme was used at a final concentration of 1.0-10 μ9/π>1.

Substrate: Peptide of sequence: Ala-Thr-His-Gln-Val-Tyr-Phe(N02)-Val-Arg-Lys-Ala, containing p- nitrophenylalanine (Phe(N02)). was prepared by solid phase peptide synthesis as previously described by Cheng et al. (1990) Proc. Nati. Acad. Sci. USA 87: 9660.

Stock Solutions of 10 mM were prepared in DMSO.

Inhibitory compounds were dissolved in sufficient DMSO to make 2.5 or 25 mM stock Solutions. Ali further dilutions were done in DMSO.

Reactions:

Compound (1-5 μυ and HIV protease were mixed in buffer containing 50 mM MES, pH 6.5, 1 M NaCl, 1 mM EDTA, 1 mM dithiothreitol, 10% glycerol. Reactions were initiated by the addition of peptide substrate to a final concentration of 240 μΜ, and absorbance at 300 nM monitored for 10 min. Values of Ki for inhibitor binding were determined from percent activity measurements in the presence and absence of knovm concentration of inhibitor, using a value of 0.07 mM for the Km of the substrate (Cheng et al. (1990) Proc. Nati. Acad. Sci. USA 87: 9660).

The HIV-1 protease inhibitory activity of representative compounds of the invention is shown in Table 1 (above). 62

Hiy-Yifild.J^3uctign Celi -Assav

Materials: MT-2, a human T-cell line, was cultured in KPMI medium supplemented with 5% (v/v) heat 5 inactivated fetal calf serum (FCS), L-glutamine and gentamycin. Human immunodeficiency virus strains, HIV (3B) and HIV(RF) were propagated in H-9 celis in rpmi with 5% FCS. Poly-L-lysine (Sigma) coated celi culture plates were prepared according to the method'of Harada 10 et al. (1985) Science 229: 563-566. MTT, 3-(4,5- dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide, was obtained from Sigma.

Method: Tēst ccmpounds were dissolved in dimethylsulfoxide to 5 mg/mL and serially diluted into 15 RPMI medium to ten times the desired final concentration. MT-2 celis (5 x lO^/mL) in 2.3 mL were mixed with 0.3 ml of the appropriate tēst compound solution and allowed to sit for 30 minūtes at roora temperature. HIV (3B) or HIV (RF) (-5 x 10^ placpje 20 forming units/mL) in 0.375 ml was added to the celi and compound mixtures and incubated for one hour at 36°C.

The mixtures'were centrifuged at 1000 rpm for 10 minūtes and the supernatants containing unattached virus were discarded. The celi pellets were suspended in fresh RPMI 25 containing the appropriate concentrations of tēst compound and placed in a 36°C, 4% C02 incubator. Virus was allowed to replicate for 3 days. Culturēs were centrifuged for 10 minūtes at 1000 rpm and the supernatants containing celi free progeny virus were 30 removed for plaque assay. <.

The virus titers of the progeny virus produced in the presence or absence of tēst compounds were determined by plaque assay. Progeny virus suspensions were serially diluted in RPMI and 1.0 mL of each 35 dilution was added to 9 ml of MT-2 celis in RPMI. Celis 63 LV 10096 and virus were incubated for 3 hours at 36°C to allow for efficient attachment of the virus to celis. Each virus and celi mixture was aliquoted equally to two wells of a six well poly-L-lysine coated culture plate 5 and incubated overnight at 36°C, 4% C02· Liquid and unattached celis were removed prior to the addition of 1.5 mL of RPMI with 0.75% (w/v) Seaplague agarose (FMC Corp.) and 5% FCS. Plates were incubated for 3 days and a second RPMI/agarose overlay was added. After an 10 additional 3 days at 36°C, 41 C02, a final overlay of phosphate-buffered saline with 0.75% Seaplaque agarose and 1 mg MTT/mL was added. The plates were incubated overnight at 36°C. Clear plaques on a purple background were counted and the number of plaque forming units of 15 virus was calculated for each sample. The antiviral activity of tēst compounds was determined by the percent reduction in the virus titer with respect to virus grown in the absence of any inhibitors. 20 HIV Low Multiolicitv Assav

Materials: MT-2, a human T-cell line, was cultured in RPMI medium supplemented with 5% (v/v) heat inactivated fetal calf serum (FCS), L-glutamine and 25 gentaraycin (GIBCO). Human immunodeficiency virus strains HIV (3B) and HIV (RF) were propagated in H-9 celis in RPMI with 5% FCS. ΧΤΤ, benzene-sulfonic acid, 3,3' - [1- [ (phenyl-amino)carbonyl] -3, 4-tetrazolium]bis(4-methoxy-6-nitro)-, sodium salt, was obtained from Stārks 30 Associates, Inc.

Method: Tēst compounds were dissolved in dimethyl-sulfoxide to 5 mg/ml and serially diluted into RPMI medium to ten times the desired final concentration. MT-2 celis (5 x loVo.l mL) were added to each well of a 96 well culture plate and 0.02 mL of the appropriate 35 64 tēst compound solution was added to the celis such that each compound concentration was present in two wells.

The celis and compounds were allowed to sit for 30 minūtes at roora temperature. HIV(3B) or HIV(RF) (-5 x 5 10^ plaque forming units/mL) was diluted in medium and added to the celi and compound mixtures to give a multiplicity of infection of 0.01 plaque forming unit/cell. The mixtures were incubated for 7 days at 36°C, during which time the virus replicated and caused 10 the death of unprotected celis. The percentage of celis protected from virus induced celi death was determined by the degree of metabolism of the tetrazolium dye, ΧΤΤ. in living celis, ΧΤΤ was metabolized to a colored formazan product which was quantitated 15 spectrophotometrically at 450 nm. The amount of colored formazan was proportional to the number of celis protected from virus by the tēst compound. The concentration of compound protecting either 50% (IC50) or 90% (IC90) with respect to an uninfected celi culture 20 was determined.

The HIV inhibitory activity of representative compounds of the present invention in the whole celi infectivity assay described above is shown in Table 2. 25 Table 2

Example Number IC9o 1C +++ IX +++ 30 IZ 4++ 1AC +++ 1AF +++ 1AH +++ + + +

1AQ 4 5 5 65 LV 10096

The IC90 values in Table 2 are indicated as: +++ s <10 pg/mL.

Dosage and Formulation

The antiviral compounds of this invention can be administered as treatment for virai infections by any means that producēs contact of the active aģent with the aģent's site of action, the virai protease, in the body 10 of a mammai. They can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic aģents or in a combination of therapeutic aģents. They can be administered alone, but generally administered with a 15 pharmaceutical carrier selected on the basis of the chosen route of administration and Standard pharmaceutical practice.

The dosage administered will, of course, vary depending upon known factors, such as the 20 pharmacodynamic characteristics of the particular aģent and its mode and route of administration; the age, health and veiģht of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect 25 desired. A daily dosage of active ingredient can be expected to be about 0.001 to 1000 milligrams per kilogram of body weight, with the preferred dose being 0.1 to about 30 mg/kg.

Dosage forms (compositions suitable for 30 administration contain from about 1 milligram to about , 100 milligrams of active ingredient per unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by veight based on the total weight of the composition. 66

The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as elixirs, syrups, and suspensions. It can also be administered parenterally, in sterile liguid dosage forms.

Gelatin capsules contain the active ingredient and powdered carriers, such as lactose, starch.cellulose derivatives, magne'sium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours.

Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.

In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar Solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral Solutions.

Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing aģents, and if necessary, buffer substances. Antioxidizing aģents such as sodium. bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing aģents.

Also used are citric acid and its salts and sodium edta. «

In addition, parenteral Solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol. 67 LV 10096

Suitable pharmaceutical carriers are described in Remington1s Pharmaceutical Sciences. Mack Publishing Company, a Standard reference text in this field.

Useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follovs:

Capsules A large number of unit capsules are prepared by filling Standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate. go.lt ..ceļat in Capsules A mixture of active ingredient in a digestable oil such as soybean oil, cottonseed oil or olive oil is prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules are vashed and dried.

Tablets A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 milligrams of active ingredient, 0.2 milligrams of colloidal Silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase « palatability or delay absorption.

Tables 3-16 below set forth representative compounds of the present invention.

Scheme.

S

LV 10096 70

Iablg-3 TABLE 3 R» /**

N HO OH R4 * R7; R22· R23 Example E4--_JS7 E22 . Number 1 benzyl allyl 2 l-pyrolylmethyl allyl 3 l-pyrazolylmethyl allyl 4 1-imidazolylmethy1 allyl 5 l-indolylmethyl allyl 6 1-triazolylmethyl allyl 7 l-tetrazolylmethyl allyl 8 •2-pyridylroethyl allyl 9 3-pyridylroethyl allyl 10 4 -py r idylnvethyl allyl 11 cyclohexylinethyl allyl 12 2-naphthylmethyl allyl 13 3-naphthylmethyl allyl 14 2-thiophenylmethyl allyl 15 4-(l-methyl)piperidinyl- allyl 16 methyl *0/4- allyl methylenedioxyphenyl)methyl 17 2-thienylmethy1 allyl 18 4-biphenylmethyl allyl 19 pyriraidinylmethyl allyl 20 2-benzothiazolylmethyl allyl 21 2-benzothiophenylmethyl allyl 22 2-thiomethylethyl allyl 23 2-thiomethylmethy1 allyl 24 2-methylpropyl allyl 25 2-methylbutyl allyl 71labie 3 26 3-methylbutyl allyl 27 cyclopropylmethyl allyl 28 cyclobutylroethyl allyl 29 cyclopentylroethyl allyl 30 p-hydroxyphenylmethyl allyl 31 p-nitrophenylmethyl allyl 32 p-aminophenylmethyl allyl 33 "4-(N,N- dimethylamino) phenylmethyl" allyl 34 benzyl propyl 35 l-pyrolylmethyl propyl 36 l-pyrazolylavethyl propyl 37 1 - imi da z o ly lme t hy 1 propyl 38 l-indolylmethyl propyl 39 l-triazolylmethyl propyl 40 1-tet ra zolylxnethyl propyl 41 2-pyridylroethyl propyl 42 3-pyridylmethyl propyl 43 4-pyridylmethyl propyl 44 cyclohexylmethyl propyl 45 2-naphthylmethyl propyl 46 3-naphthylmethyl propyl 47 2-thiophenylmethyl propyl 48 4- (l-methyl)piperidinyl-methyl propyl 49 "(3,4- methylenedioxyphenyl) methyl" propyl 50 2-thienylmethyl propyl 51 4-biphenylmethyl propyl 52 pyriird.dinylmethyl propyl 53 2-benzothiazolylmethyl propyl 54 2-benzothiophenylmethyl propyl 55 2-thiomethylethyl propyl 56 2-thiomethylmethyl propyl 57 2rmethylpropyl propyl 58 2-methylbutyl propyl 59 3-methylbutyl propyl 60 cyclopropyl»ethyl propyl 61 cyclobutylmethyl propyl 62 cyclopentylmethyl propyl 63 p-hydroxyphenylmethyl propyl 64 p-nitrophenylmethyl propyl 65 p-aminophenylmethyl propyl 66 "4-(N,M- dimethylamino) phenylmethyl" propyl 67 benzyl n-butyl 68 l-pyrolylmethyl n-butyl 69 l-pyrazolylmethyl n-butyl 70 l-imidazolylmethyl n-butyl 71 l-indolylmethyl n-butyl 72 l-triazolylmethyl n-butyl 73 l-tetrazolylmethyl n-butyl 74 2-pyridylmethyl n-butyl 75 3-pyridylmethyl n-butyl LV 10096 72

labie -J 76 •4-pyridylmethyl n-butyl 77 cyclohexylmethyl n-butyl 78 2-naphthylmethyl n-butyl 79 3-naphthylmethyl n-butyl 80 2-thiophenylmethyl n-butyl 81 4-(l-methyl)piperidinyl- methyl n-butyl 82 "(3,4- methylenedioxyphenyl)roethyl" n-butyl 83 2-thienylmethyl n-butyl 84 4-biphenylmethyl n-butyl 85 pyrimidinylmethyl n-butyl 86 2-benzothiazolylmethyl n-butyl 87 2-benzothiophenylmethyl n-butyl 88 2-thiomethylethyl n-butyl 89 2-thiomethylmethyl n-butyl 90 2-methylpropyl n-butyl 91 2-methylbutyl n-butyl 92 3-methylbutyl n-butyl 93 cyclopropylmethyl n-butyl 94 cyclobutylmethyl n-butyl 95 cyclopentylmethyl n-butyl 96 p-hydroxyphenylmethyl n-butyl 97 p-nitrophenylmethyl n-butyl 98 p-aminophenylmethyl n-butyl 99 "4-(N,N- dimethylamino) phenylmethyl" n-butyl 100 benzyl isobutyl 101 l-pyrolyLnethyl isobutyl 102 l-pyrazolylmethyl isobutyl 103 1-imidazoly lmethy1 isobutyl 104 l-indolylmethyl isobutyl 105 l-triazolylmethyl isobutyl 106 l-tetrazolylmethyl isobutyl 107 2-pyridylmethyl isobutyl 108 3-pyridylinethyl isobutyl 109 4-pyridylmethyl iaobutyl 110 cyclohexylmethyl isobutyl 111 2-naphthylmethyl isobutyl 112 3-naphthylroethyl iaobutyl 113 2-thiophenylniethyl iaobutyl 114 4-(l-methyl)piperidinyl- methyl isobutyl 115 "(3,4- methylenedioxyphenyl) methyl" iaobutyl 116 2-thienylmethyl isobutyl 117 4-blphenylxnethyl isobutyl 118 pyrimidinylmethyl isobutyl 119 2-benzothiazolylmethyl isobutyl 120 2-benzothiophenylmethyl isobutyl 121 2-thiomethylethyl isobutyl 122 2-thiomethyljnethyl isobutyl 123 2-methylpropyl isobutyl 124 2-methylbutyl isobutyl 73 LV 10096 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174

Table 3 3-methylbutyl lsobutyl cyclopropylmethyl isobutyl cyclobutylmethyl isobutyl cyclopentylmethyl iaobutyl p-hydroxyphenylmethyl isobutyl p-nitrophenylmethyl isobutyl p-aminophenylmethyl isobutyl isobutyl dimethylaaino) phenylaethyl" benzyl 2-butyl l-pyrolylmethyl 2-butyl l-pyrazolylmethyl 2-butyl l-imidazolylaethyl 2-butyl l-indolylmethyl 2-butyl l-triazolylroethyl 2-butyl l-tetrazolylmethyl 2-butyl 2-pyridylmethyl 2-butyl 3-pyridylmethyl 2-butyl 4-pyridylmethyl 2-butyl cyclohexylmethyl 2-butyl 2-naphthylmethyl 2-butyl 3-naphthylroethyl 2-butyl 2-thiophenylmethyl 2-butyl 4- (l-methyl)piperidinyl- 2-butyl methyl "(3,4- 2-butyl methylenedioxyphenyl)methyl" 2-thienylmethyl 2-butyl 4-biphenylmethyl 2-butyl pyrimidinylmethyl 2-butyl 2-benzothiazolylmethyl 2-butyl 2-benzothiophenylmethyl 2-butyl 2-thiomethylethyl 2-butyl 2-thiomethylmethyl 2-butyl 2-methylpropyl 2-butyl 2-methylbutyl 2-butyl 3-methylbutyl 2-butyl cyclopropylmethyl 2-butyl cyclobutylmethyl 2-butyl cyclopentylmethyl 2-butyl p-hydroxyphenylmethyl 2-butyl p-nitrophenylinethyl 2-butyl p-aminophenylmethyl 2-butyl •4-(N,N- 2-butyl dimethylamino) phenylmethyl benzyl 1-pyrolylmethyl 1-pyrazolylmethy1 1-imidazoly lmethy1 l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethy1 3- pyridylmethyl *3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl" "3,3-dimethallyl* 74 labie 3 175 . 4-pyridylmethyl "3,3-dimethallyl" 176 cyclohexylmethyl "3,3-dimethallyl" 177 2-naphthylraethyl "3,3-dimethallyl" 178 3-naphthylroethyl ,· "3,3-dimethallyl" 179 2-thiophenylmethyl "3,3-dimethallyl" 180 4- (l-methyl)piperidinyl-methyl "3,3-dimethallyl" 181 "(3,4- methylenedioxyphenyl) methyl" "3,3-dimethallyl" 182 2-thienylmethyl "3,3-dimethallyl" 183 4-biphenylmethy1 "3,3-dimethallyl" 184 pyrind.dinylmethyl "3,3-dimethallyl" 185 2-benzothlazolylmethyl "3,3-dimethallyl" 186 2-benzothiophenylmethyl "3,3-dimethallyl" 187 2-thiomethylethyl "3,3-dimethallyl" 188 2-thiomethylmethyl "3,3-dimethallyl" 189 2-methylpropyl "3,3-dimethallyl" 190 2-methylbutyl "3,3-dimethallyl* 191 3-methylbutyl "3,3-dimethallyl" 192 cyclopropylmethyl "3,3-dimethallyl" 193 cyc1obut ylmet hy1 "3,3-dimethallyl" 194 cyclopentylmethyl "3,3-dimethallyl" 195 p-hydroxyphenylroethyl "3,3-dimethallyl" 196 p-nitrophenylmethyl "3,3-dimethallyl" 197 p-aminophenylmethyl "3,3-dimethallyl" 198 "4-(N,N- dimethylamino)phenylmethyl" "3,3-dimethallyl" 199 benzyl 3-methallyl 200 l-pyrolylmethyl 3-methallyl 201 l-pyrazolylmethyl 3-methallyl 202 1 - imi da z o ly lme t hy 1 3-methallyl 203 l-indolylmethyl 3-methallyl 204 l-triazolylmethyl 3-methallyl 205 l-tetrazolylmethyl 3-methallyl 206 2-pyridylmethyl 3-methallyl 207 3-pyridylmethyl 3-methallyl 208 4-pyridylmethyl 3-methallyl 209 cyclohexylmethyl 3-methallyl 210 2-naphthylmethyl 3-methallyl 211 3-naphthylmethyl 3-methallyl 212 2-thiophenylmethyl 3-methallyl 213 4-(l-methyl)piperidinyl- methyl 3-methallyl 214 "(3,4- methylenedioxyphenyl) methyl· 3-methallyl 215 2-thienylmethyl 3-methallyl 216 4-biphenylmethyl 3-methallyl 217 pyrimidinylmethyl 3-methallyl 218 2-benzothiazolylmethyl 3-methallyl 219 2 -benzothiopheny lmethyl 3-methallyl 220 2-thiomethylethyl 3-methallyl 221 2-thiomethylmethyl 3-methallyl 222 2-methylpropyl 3-methallyl 223 2-methylbutyl 3-methallyl 75 75 LV 10096

Table-3 224 3-methylbutyl 3-methallyl 225 cyclopropylmethyl 3-methallyl 226 cyclobutylmethyl 3-methallyl 227 cyclopentylmethyl 3-methallyl 228 p-hydroxyphenylmethyl 3-methallyl 229 p-nitrophenylmethyl 3-methallyl 230 p-aminophenylmethyl 3-methallyl 231 "4-(N/N- dimethylamino) phenylmethyl" 3-methallyl 232 benzyl 2-methallyl 233 l-pyrolylmethyl 2-methallyl 234 1-pyrazolylmethyl 2-methallyl 235 l-imidazolylmethyl 2-methallyl 236 l-indolylmethyl 2-methallyl 237 l-triazolylmethyl 2-methallyl 238 l-tetrazolylmethyl 2-methallyl 239 2-pyridylmethyl 2-methallyl 240 3-pyridylmethyl 2-methallyl 241 4-pyridylmethyl 2-methallyl 242 cyclohexylroethyl 2-methallyl 243 2-naphthylmethyl 2-methallyl 244 3-naphthylmethyl 2-methallyl 245 2-thiophenylmethyl 2-methallyl 246 4- (l-methyl)piperidinyl-methyl 2-methallyl 247 "(3,4- methylenedioxyphenyl)methyl" 2-methallyl 248 2-thienylmethyl 2-methallyl 249 4-biphenylmethyl 2-methallyl 250 pyrimidinylmethyl 2-methallyl 251 2-benzothiazolylmethyl 2-methallyl 252 2-benzothiophenylmethyl 2-methallyl 253 2-thiomethylethyl 2-methallyl 254 2-thiomethylmethyl 2-methallyl 255 2-methylpropyl 2-methallyl 256 2-methylbutyl 2-methallyl 257 3-methylbutyl 2-methallyl 258 cyclopropylmethyl 2-methallyl 259 cyclobutylmethyl 2-methallyl 260 cyclopentylmethyl 2-methallyl 261 p-hydroxyphenylmethyl 2-methallyl 262 p-nitrophenylmethyl 2-methallyl 263 p-aminophenylmethyl 2-methallyl 264 "4-{N,N- dimethylami.no) phenylmethyl" 2-methallyl 265 benzyl 2-propyl 266 l-pyrolylmethyl 2-propyl 267 l-pyrazolylmethyl 2-propyl 268 1-imida zoly lme thyl 2-propyl 269 l-indolylinethyl 2-propyl 270 l-triazolylmethyl 2-propyl 271 l-tetrazolylmethyl 2-propyl 272 2-pyridylmethyl 2-propyl 273 3-pyridylmethyl 2-propyl 76

Table-3 274 ' 4-pyridylmethyl 2-propyl 275 cyclohexyl»ethyl 2-propyl 276 2-naphthylmethy1 2-propyl 277 3-naphthylmethyl 2-propyl 278 2-thiophenylmethyl 2-propyl 279 4-(l-methyl) piperidinyl-methyl 2-propyl 280 "(3,4- methylenedioxyphenyl) methyl" 2-propyl 281 2-thienylmethyl 2-propyl 282 4-biphenylmethyl 2-propyl 283 pyrimidinylflvethyl 2-propyl 284 2-benzothiazolylmethyl 2-propyl 285 2-benzothiophenylmethyl 2-propyl 286 2-thiomethylethyl 2-propyl 287 2-thiomethylmethyl 2-propyl 288 2-methylpropyl 2-propyl 289 2-methylbutyl 2-propyl 290 3-methylbutyl 2-propyl 291 cyclopropylroethyl 2-propyl 292 cyclobutylmethyl 2-propyl 293 cyclopentylmethyl 2-propyl 294 p-hydroxyphenylmethyl 2-propyl 295 p-nitrophenylmethyl 2-propyl 296 p-aminophenylmethyl 2-propyl 297 4-(N,N- dimethylamino) phenylmethyl" 2-propyl 298 benzyl cyclopropyl 299 l-pyrolylmethyl cyclopropyl 300 l-pyrazolylmethyl cyclopropyl 301 l-imidazolylmethyl cyclopropyl 302 l-indolylinethyl cyclepropyl 303 l-triazolylmethyl cyclopropyl 304 l-tetrazolylmethyl cyclopropyl 305 2-pyridylmethyl cyclopropyl 306 3-pyridylmethyl cyclopropyl 307 4-pyridylxnethyl cyclopropyl 308 cyclohexylmethyl cyclopropyl 309 2-naphthylmethyl cyclopropyl 310 3-naphthylmethy1 cyclopropyl 311 2-thiophenylmethyl cyclopropyl 312 4-(l-methyl)piperidinyl- methyl cyclopropyl 313 "(3,4- methylenedioxyphenyl) methyl" cyclopropyl 314 2-thienylroethyl cyclopropyl 315 4-biphenylmethy1 cyclopropyl 316 pyrimidinylmethyl cyclopropyl 317 2-benzothiazolylrnethyl cyclopropyl 318 2-benzothiophenylmethyl cyclopropyl 319 2-thiomethylethyl cyclopropyl 320 2-thlomethylroethyl cyclopropyl 321 2-methylpropyl cyclopropyl 322 2-»ethylbutyl cyclopropyl 77 LV 10096

Table 3 323 3-methylbutyl cyclopropyl 324 cyclopropylmethyl cyclopropyl 325 cyclobutylmethyl cyclopropyl 326 cyclopentylmethyl cyclopropyl 327 p-hydroxyphenylmethyl cyclopropyl 328 p-nitrophenylmethyl cyclopropyl 329 p-aminophenylmethyl cyclopropyl 330 "4-(N,N- dimethylamino) phenylmethyl" cyclopropyl 331 benzyl cyclopropylmethyl 332 l-pyrolylmethyl cyclopropylmethyl 333 l-pyrazolylmethyl cyclopropylmethyl 334 1 -imida zolylmethyl cyclopropylmethyl 335 l-indolylmethyl cyclopropylmethyl 336 l-triazolylmethyl cyclopropylmethyl 337 l-tetrazolylmethyl cyclopropylmethyl 338 2-pyridylmethyl cyclopropylmethyl 339 3-pyridylmethyl cyclopropylmethyl 340 4-pyridylmethyl cyclopropylmethyl 341 cyclohexylmethyl cyclopropylmethyl 342 2-naphthylmethyl cyclopropylmethyl 343 3-naphthylmethyl cyclopropylmethyl 344 2-thiophenylmethyl cyclopropylmethyl 345 4-(l-methyl)piperidinyl-methyl cyc1opropylmethy1 346 "(3,4- methylenedioxyphenyl)methyl" cyclopropylmethyl 347 2-thienylmethyl cyclopropylmethyl 348 4 -biphenylmethy1 cyclopropylmethyl 349 pyrimidinylmethyl cyclopropylmethyl 350 2-benzothiazolylmethyl cyclopropylmethyl 351 2-benzothiophenylmethyl cyclopropylmethyl 352 2-thiomethylethyl cyclopropylmethyl 353 2-thiomethylmethyl cyclopropylmethyl 354 2-roethylpropyl cyclopropylmethyl 355 2-methylbutyl cyclopropylmethyl 356 3-methylbutyl cyclopropylmethyl 357 cyclopropylmethyl cyclopropylmethyl 358 cyclobutylmethyl cyclopropylmethyl 359 cyclopentylmethyl cyclopropylmethyl 360 p-hydroxyphenylmethyl cyclopropylmethyl 361 p-nitrophenylmethyl cyclopropylmethyl 362 p -aminophe ny lme t hy 1 cyclopropylmethyl 363 "4-<N,N- dimethylami.no) phenylmethyl" cyc1op ropylmethyl 364 benzyl n-pentyl 365 1 -pyrolylmethyl n-pentyl 366 l-pyrazolylmethyl n-pentyl 367 l-imidazolylmethyl n-pentyl 368 l-indolylmethyl n-pentyl 369 l-triazolylmethyl n-pentyl 370 l-tetrazolylmethyl n-pentyl 371 2-pyridylmethyl n-pentyl 372 3-pyridylmethyl n-pentyl 78 labie 3 373 4-pyridylmethyl n-pentyl 374 cyclohexylmethyl n-pentyl 375 2-naphthylmethyl n-pentyl 376 3-naphthylmethy1 n-pentyl 377 2-thiophenylmethyl n-pentyl 378 4-(l-methyl)piperidinyl-methyl n-pentyl 379 "(3,4- methylenedioxyphenyl) methyl" n-pentyl 380 2-thienylmethy1 n-pentyl 381 4-biphenyl®ethy1 n-pentyl 382 py r imidiny lmethyl n-pentyl 383 2-benzothiazolylmethyl n-pentyl 384 2-benzothiophenylmethyl n-pentyl 385 2-thiomethylethyl n-pentyl 386 2-thiomethylmethyl n-pentyl 387 2-methylpropyl n-pentyl 388 2-methylbutyl n-pentyl 389 3-methylbutyl n-pentyl 390 cyclopropylmethyl n-pentyl 391 cyclobutylmethyl n-pentyl 392 cyclopentylmethyl n-pentyl 393 p-hydroxyphenylmethyl n-pentyl 394 p-nitrophenylmethyl n-pentyl 395 p-aminophenylinethyl n-pentyl 396 "4-{N,N- dimethylajtdno) phenylmethyl" n-pentyl 397 benzyl 2-pentyl 398 1-pyrolylroethy1 2-pentyl 399 l-pyrazolylroethyl 2-pentyl 400 1 - imida zoly lwethy 1 2-pentyl 401 l-indolylmethyl 2-pentyl 402 1-triazolylmethyl 2-pentyl 403 l-tetrazolylmethyl 2-pentyl 404 2-pyridylinethyl 2-pentyl 405 3-pyridylmethyl 2-pentyl 406 4 -pyr idylmethyl 2-pentyl 407 cyclohexylmethyl 2-pentyl 408 2-naphthy lmethy1 2-pentyl 409 3-naphthylmethyl 2-pentyl 410 2-thiophenylmethyl 2-pentyl 411 4- (l-methyl)piperidinyl-methyl 2-pentyl 412 "<3,4- 2-pentyl methylenedioxyphenyl)methyl" 2-pentyl 413 2-thienylmethyl 414 4-biphenyl»ethyl 2-pentyl 415 pyrijnldinylmethyl 2-pentyl 416 2-benzothiazolylmethyl 2-pentyl 417 2-benzothiophenylmethyl 2-pentyl 418 2-thiomethylethyl 2-pentyl 419 2-thiomethylmethyl 2-pentyl 420 2-methylpropyl 2-pentyl 421 2-roethylbutyl 2-pentyl 80LV 10096

Table 3 472 ' 4-pyridylroethyl 3-methylbutyl 473 cyclohexylmethyl 3-methylbutyl 474 2-naphthylmethyl 3-methylbutyl 475 3-naphthylmethyl ,· 3-methylbutyl 476 2-thiophenylmethyl 3-methylbutyl 477 4-(l-methyl)piperidinyl- methyl 3-methylbutyl 478 "(3,4- methylenedioxyphenyl) methyl" 3-methylbutyl 479 2-thienyljnethyl 3-methylbutyl 480 4-biphenylmethyl 3-methylbutyl 481 pyrimidinylroethyl 3-methylbutyI 482 2-benzothiazolylmethyl 3-methylbutyl 483 2-benzothiophenylinethyl 3-methylbutyl 484 2-thiomethylethyl 3-methylbutyl 485 2-thiomethylinethyl 3-methylbutyl 486 2-methylpropyl 3-methylbutyl 487 2-methylbutyl 3-methylbutyl 488 3-methylbutyl 3-methylbutyl 489 cyclopropyLnethyl 3-methylbutyl 490 cyclobutylinethyl 3-methylbutyl 491 cyclopentylmethyl 3-methylbutyl 4 92 p-hydroxyphenylmethyl 3-methylbutyl 493 p-nitrophenylmethyl 3-methylbutyl 494 p-aminophenylmethyl 3-methylbutyl 495 "4-{N,N- dimethylandno) phenylmethyl" 3-methylbutyl 496 benzyl 2-methylbutyl 497 l-pyrolylmethyl 2-methylbutyl 498 l-pyrazolylmethyl 2-methylbutyl 499 1-imida zolylmethy 1 2-methylbutyl 500 l-indolylmethyl 2-methylbutyl 501 l-triazo'lylmethyl 2-methylbutyl 502 l-tetrazolyl»ethyl 2-methylbutyl 503 2-pyridylmethyl 2-methylbutyl 504 3-pyridylmethyl 2-methylbutyl 505 4-pyridylmethyl 2-methylbutyl 506 cyclohexylmethyl 2-methylbutyl 507 2-naphthylroethyl 2-methylbutyl 508 3-naphthylmethyl 2-methylbutyl 509 2-thiophenylmethyl 2-methylbutyl 510 4-{l-methyl)piperidinyl- methyl 2-methylbutyl 511 "(3,4- methylenedioxyphenyl)methyl" 2-methylbutyl 512 2 -thienylnvethyl 2-methylbutyl 513 4-biphenylmethyl 2-methylbutyl 514 pyriraidinylmethyl 2-methylbutyl 515 2-benzothiazolylmethyl 2-methylbutyl 516 2-benzothiophenylmethyl 2-methylbutyl 517 2-thiomethylethyl 2-methylbutyl 518 2-thiomethylnvethyl 2-methylbutyl 519 2-methylpropyl 2-methylbutyl 520 2-methylbutyl 2-methylbutyl

I 81 labie 3 521 3-methylbutyl 2-methylbutyl 522 cyclopropylmethyl 2-methylbutyl 523 cyclobutylmethyl 2-methylbutyl 524 cyclopentylmethyl 2^methylbutyl 525 p-hydroxyphenylmethyl 2-methylbutyl 526 p-nit rophenylmethyl 2-methylbutyl 527 p-aminophenylmethyl 2-methylbutyl 528 *4-(N,N- dimethylamino) phenylmethyl" 2-methylbutyl 529 benzyl propargyl 530 l-pyrolylmethyl propargyl 531 l-pyrazolylmethyl propargyl 532 l-imidazolylinethyl propargyl 533 l-indolylmethyl propargyl 534 l-triazolylmethyl propargyl 535 l-tetrazolylmethyl propargyl 536 2-pyridylmethyl propargyl 537 3-pyridylmethyl propargyl 538 4-pyr idylmethyl propargyl 539 cyclohexylmethyl propargyl 540 2-naphthylmethyl propargyl‘ 541 3-naphthylmethyl propargyl 542 2-thiophenylmethyl propargyl 543 4- (l-methyl)piperidinyl-methyl propargyl 544 •(3,4- methylenedioxyphenyl)methyl" propargyl 545 2-thienylmethyl propargyl 546 4-biphenylmethyl propargyl 547 pyrimidinylxnethyl propargyl 548 2-benzothiazolylmethyl propargyl 549 2-benzothiophenylmethyl propargyl 550 2-thiomethylethyl propargyl 551 2-thiomethy lmethyl propargyl 552 2-methylpropyl propargyl 553 2-methylbutyl propargyl 554 3-methylbutyl propargyl 555 cyclopropylmethyl propargyl 556 cyclobutylmethyl propargyl 557 cyclopentylmethyl propargyl 558 p-hydroxyphenylmethyl propargyl 559 p-nitrophenylmethyl propargyl 560 p-aminophenylmethyl propargyl 561 "4-(N,N- dimethyland.no) phenylmethyl" propargyl 562 benzyl cyclobutyl 563 1-pyrolylmethyl cyclobutyl 564 l-pyrazolylmethyl cyclobutyl 565 l-imidazolylmethyl cyclobutyl 566 l-indolylmethyl cyclobutyl 567 l-triazolylmethyl cyclobutyl 568 l-tetrazolylmethyl cyclobutyl 569 2-pyridylmethyl cyclobutyl 570 3-pyridylmethyl cyclobutyl 82Tahļf» 3 LV 10096 571 4-pyridy]jnethyl cyclobutyj. 572 cyclohexylmethyl cyclobutyl 573 2-naphthylmethy1 cyclobutyl 574 3-naphthylmethyl cyclobutyl 575 2-thiophenylmethyl cyclobutyl 576 4-(l-methyl)piperidinyl-methyl cyclobutyl 577 "(3,4- methylenedioxyphenyl)methyl" cyclobutyl 578 2-thienylmethyl cyclobutyl 579 4-bipheny lmethyl cyclobutyl 580 py r imidi ny lme t hy 1 cyclobutyl 581 2-benzothiazolyljnethyl cyclobutyl 582 2-benzothiophenylmethyl cyclobutyl 583 2-thiomethylethyl cyclobutyl 584 2-thiomethylmethyl cyclobutyl 585 2-methylpropyl cyclobutyl 586 2-methylbutyl cyclobutyl 587 3-n>ethylbutyl cyclobutyl 588 cyclopropylmethyl cyclobutyl 589 cyclobutylmethyl cyclobutyl 590 cyclopentylmethyl cyclobutyl 591 p-hydroxyphenylmethyl cyclobutyl 592 p-nitrophenylmethyl cyclobutyl 593 p-aminophenylmethyl cyclobutyl 594 "4-(N,N- dimethylamino)phenylmethyl" cyc!obutyl 595 benzyl cyclobutylmethyl 596 l-pyrolylmethyl cyclobutylmethyl 597 l-pyrazolyl®ethyl cyclobutylmethyl 598 1-imida zolyLnethyl cyclobutylmethyl 599 l-indolylmethyl cyclobutylmethyl 600 l-triazolylmethyl cyclobutylmethyl 601 l-tetrazolylmethyl cyclobutylmethyl 602 2-pyridylmethyl cyclobutylmethyl 603 3-pyridylroethyl cyclobutylmethyl 604 4-pyridylmethyl cyclobutylmethyl 605 cyclohexylmethyl cyclobutylmethyl 606 2-naphthylnvethyl cyclobutylmethyl 607 3-naphthylmethyl cyclobutylmethyl 608 2-thiophenylmethyl cyclobutylinethyl 609 4-(l-methyl)piperidinyl-methyl cyclobutylmethyl 610 "{3,4- methylenedioxyphenyl)methyl" cyclobutylmethyl 611 2-thienylmethyl cyclobutylmethyl 612 4-biphenylmethyl cyclobutylmethyl 613 pyrimidinylmethyl cyclobutylmethyl 614 2-benzothiazolylmethyl cyclobutylmethyl 615 2-benzothiophenylxnethyl cyclobutylmethyl 616 2-thiomethylethyl cyclobutylmethyl 617 2-thiomethylmethyl cyclobutylxnethyl 618 2-methylpropyl cyclobutylmethyl 619 2-methylbutyl cyclobutylnvethyl 83

Jable 3 620 '3-methylbutyl cyclobutylmethyl 621 cyclopropylmethyl cyclobutylmethyl 622 cyclobutylmethyl cyclobutylmethyl 623 cyclopentylmethyl cyclobutylmethyl 624 p-hydroxyphenylmethyl cyclobutylmethyl 625 p-nitrophenylmethyl cyclobutylmethyl 626 p-aminophenylmethyl cyclobutylmethyl 627 "4-(N,N- dimethylami.no) phenylmethyl" cyclobutylmethyl 628 benzyl cyclopentyl 629 l-pyrolylmethyl cyclopentyl 630 l-pyrazolylroethyl cyclopentyl 631 l-imidazolJrlmethyl cyclopentyl 632 l-indolylmethyl cyclopentyl 633 l-triazolylmethyl cyclopentyl 634 l-tetrazolylmethyl cyclopentyl 635 2-pyridylmethyl cyclopentyl 636 3-pyridylmethyl cyclopentyl 637 4-pyridylmethyl cyclopentyl 638 cyclohexylmethyl cyclopentyl 639 · 2-naphthylmethyl cyclopentyl 640 3-naphthylmethyl cyclopentyl 641 2-thiophenylmethyl cyclopentyl 642 4-{l-methyl)piperidinyl- methyl cyclopentyl 643 "(3,4- methylenedioxyphenyl) methyl" cyclopentyl 644 2-thienylmethyl cyclopentyl 645 4-biphenylmethyl cyclopentyl 64 6 pyrimidinylmethyl cyclopentyl 647 2-benzothiazolylmethyl cyclopentyl 648 2-benzothiophenylmethyl cyclopentyl 649 2-thiomethylethyl cyclopentyl 650 2-thiomethylmethyl cyclopentyl 651 2-methylpropyl cyclopentyl 652 2-methylbutyl cyclopentyl 653 3-methylbutyl cyclopentyl 654 cyclopropylmethyl cyclopentyl 655 cyclobutylmethyl cyclopentyl 656 cyclopentylmethyl cyclopentyl 657 p-hydroxyphenylmethyl cyclopentyl 658 p-nitrophenylmethyl cyclopentyl 659 p-aminophenylmethyl cyclopentyl 660 "4-(N,N- dimethylamino) phenylmethyl" cyclopentyl 661 benzyl cyclopentylmethyl 662 l-pyrolylmethyl cyclopentylroethyl 663 l-pyrazolylmethyl cyclopentylmethyl 664 l-imidazolylmethyl cyclopentylmethyl 665 l-indolylmethyl cyclopentylmethyl 666 l-triazolylmethyl cyclopentylmethyl 667 l-tetrazolylmethyl cyclopentylmethyl 668 2-pyridylmethyl cyclopentylxnethyl 669 3-pyridylmethyl cyclopentylmethyl 64LV 10096

Table 2 670 4-pyridylnvethyl cyclopentylmethyl 671 cyclohexylmethyl cyclopentylmethyl 672 2-naphthylmethyl ’ cyclopentylmethyl 673 3-naphthylmethyl cyclopentylmethyl 674 2-thiophenylmethyl cyclopentylmethyl. 675 4- (l-methyl)piperidinyl-methyl cyclopentylmethyl 676 "(3,4- methylenedioxyphenyl)niethyl" cyclopentylmethyl 677 2-thienylmethyl cyclopentylmethyl 678 4-biphenylmethyl cyclopentylroethyl 679 pyrimidinylmethyl cyclopentylmethyl 680 2-benzothiazolylmethyl cyclopentylmethyl 681 2-benzothiophenylmethyl cyclopentylmethyl 682 2-thiomethylethyl cyclopentylmethyl 683 2-thiomethylmethyl cyclopentylmethyl 684 2-methylpropyl cyclopentylroethyl 685 2-rnethylbutyl cyclopentylmethyl 686 3-methylbutyl cyclopentylmethyl 687 cyclopropylmethyl cyc1opentylmethy1 688 cyclobutylmethyl cyclopentylmethyl 689 cyclopentylroethyl cyclopentylmethyl 690 p-hydroxyphenylmethyl cyclopentylmethyl 691 p-nitrophenylmethyl cyclopentylmethyl 692 p-arainophenylmethyl cyclopentylmethyl 693 "4-(N,N- dimethylami.no) phenylmethyl" cyclopentylmethyl 694 benzyl l-hexyl 695 l-pyrolylmethyl l-hexyl 696 l-pyrazolylmethyl l-hexyl 697 l-imidazolylmethyl l-hexyl 698 l-indolylmethyl .l-hexyl 699 l-triazolylmethyl l-hexyl 700 l-tetrazolylmethyl l-hexyl 701 2-pyridylmethyl l-hexyl 702 3-pyridylmethyl l-hexyl 703 4-pyridylmethyl l-hexyl 704 cyclohexylmethyl l-hexyl 705 2-naphthylmethyl l-hexyl 706 3-n a ph t hy lme t hy 1 l-hexyl 707 2-thiophenylmethyl l-hexyl 708 4-{l-methyl)piperidinyl- methyl l-hexyl 709 "(3,4- methylenedioxyphenyl)methyl" l-hexyl 710 2-thienylmethyl l-hexyl 711 4-biphenylmethyl l-hexyl 712 pyrimidinylmethyl l-hexyl 713 2-benzothiazolylmethyl l-hexyl 714 2-benzothiophenylmethyl l-hexyl 715 2-thiomethylethyl l-hexyl 716 2-thiomethylmethyl l-hexyl 717 2 -methylpropyl l-hexyl 718 2-methylbutyl l-hexyl 85 lahl&Jl 719 3-methylbutyl l-hexyl 720 cyclopropylmethyl l-hexyl 721 cyclobutylmethyl l-hexyl 722 cyclopentylmethyl l-hexyl 723 p-hydroxyphenylmethyl l-hexyl 724 p-nitrophenylmethyl l-hexyl 725 p-aminophenyl®ethyl l-hexyl 726 *4-(N,N- dimethylami.no) phenylmethyl" l-hexyl 727 benzyl 4-oethylpentyl 728 l-pyrolylmethyl 4-methylpentyl 729 l-pyrazolylmethyl 4-methylpentyl 730 l-imidazolylmethyl 4-methylpentyl 731 l-indolylaethyl 4-methylpentyl 732 l-triazolylmethyl 4-methylpentyl 733 l-tetrazolylmethyl 4-methylpentyl 734 2-pyridylmethyl 4-methylpentyl 735 3-pyridylmethyl 4-methylpentyl 736 4-pyridylmethyl 4-methylpentyl 737 cyclohexylmethyl 4-nvethylpentyl 738 2-naphthylmethyl 4-methylpentyl 739 3-naphthylmethyl 4-methylpentyl 740 2-thiophenylmethyl 4-methylpentyl 741 4-(l-methyl)piperidinyl-methyl 4-methylpentyl 742 "(3,4- methylenedioxyphenyl)methyl" 4-methylpentyl 743 2-thienylmethyl 4-methylpentyl 744 4-biphenylmethyl 4-methylpentyl 745 pyrimidinylmethyl 4-methylpentyl 746 2-benzothiazolylmethyl 4-methylpentyl 747 2-benzothiophenylmethyl 4-methylpentyl 748 2-thiomethylethyl 4-methylpentyl 749 2-thiomethylmethyl 4-methylpentyl 750 2-methylpropyl 4-methylpentyl 751 2-methylbutyl 4-methylpentyl 752 3-methylbutyl 4-roethylpentyl 753 cyclopropylmethyl 4-methylpentyl 754 cyclobutylmethyl 4-methylpentyl 755 cyc 1 ope n t y lme t hy 1 4-methylpentyl 756 p-hydroxyphenylmethyl 4-methylpentyl 757 p-nitrophenylmethyl 4-methylpentyl 758 p-aminophenylmethyl 4-methylpentyl 759 4-(N,N* dimethylamino)phenylmethyl" 4-methylpentyl 760 benzyl 3-methylpentyl 761 l-pyrolylmethyl 3-methylpentyl 762 l-pyrazolylroethyl 3-methylpentyl 763 1-imidazolylmethyl 3-methylpentyl 764 l-indolylmethyl 3-methylpentyl 765 l-triazolylmethyl 3-methylpentyl 766 l-tetrazolylmethyl 3-methylpentyl 767 2-pyridylmethyl 3-methylpentyl 768 3-pyridylmethyl 3-methylpentyl 87labie„3 LV 10096 818 3-methylbutyl isopropyl 819 cyclopropylmethyl iaopropyl 820 cyclobutylmethyl· iaopropyl 821 cyclopentylroethyl iaopropyl 822 p-hydroxyphenylmethyl iaopropyl 823 p-nit rophenylmethyl isopropyl 824 p-aminophenylmethyl iaopropyl 825 *4-{N,N- diroethylami.no) phenylmethyl" iaopropyl 826 benzyl 3-roethylbutyl 827 l-pyrolylroethyl 3-methylbutyl 828 l-pyrazolylmethyl 3-roethylbutyl 829 l-imidazolylīnethyl 3-roethylbutyl 830 1-indolylroethyl 3-methylbutyl 831 l-triazolylmethyl 3-roethylbutyl 832 l-tetrazolylmethyl 3-methylbutyl 833 2-pyridylmethyl 3-roethylbutyl 834 3-pyridylroethyl 3-methylbutyl 835 4-pyridylroethyl 3-methylbutyl 836 cyclohexylroethyl 3-methylbutyl 837 2-naphthylmethyl 3-roethylbutyl 838 3-naphthylroethyl 3-methylbutyl 839 2-thiophenylmethyl 3-methylbutyl 840 4-(l-methyl)piperidinyl- methyl 3-methylbutyl 841 "(3,4- methylenedioxyphenyl) methyl" 3-methylbutyl 842 2-thienylmethyl 3-methylbutyl 843 4-biphenylmethyl 3-methylbutyl 844 pyrimidinylmethyl 3-methylbutyl 845 2-benzothiazolylmethyl 3-methylbutyl 846 2-benzothiophenylroethyl 3-methylbutyl 847 • 2-thiomethylethyl 3-methylbutyl 846 2-thiomethylroethyl 3-methylbutyl 849 2-roethylpropyl 3-methylbutyl 850 2-roethylbutyl 3-methylbutyl 851 3-methylbutyl 3-methylbutyl 852 cyclopropylmethyl 3-methylbutyl 853 cyclobutylroethyl 3-methylbutyl 854 cyclopentylmethyl 3-roethylbutyl 855 p-hydroxyphenylmethyl 3-methylbutyl 856 p-nitrophenylmethyl 3-methylbutyl 857 p-aminophenylmethyl 3-methylbutyl 858 "4-(N,N- dimethylamino) phenylmethyl* 3-methylbutyl 859 benzyl 2-phenylethyl 860 l-pyrolylroethyl 2-phenylethyl 861 l-pyrazolylmethyl 2-phenylethyl 862 l-imidazolylmethyl 2-phenylethyl 863 l-indolylmethyl 2-phenylethyl 864 l-triazolylmethyl 2-phenylethyl 865 l-tetrazolylroethyl 2-phenylethyl 866 2-pyridylroethyl 2-phenylethyl 867 3-pyridylmethyl 2-phenylethyl 86 labis 1 868 4-pyridylmethyl 2-phenylethyl 869 cyclohexylmethyl 2-phenylethyl 870 2-naphthylmethyl 2-phenylethyl 871 3-naphthylroethyl 2-phenylethyl 872 2-thiophenylmethyl 2-phenylethyl 873 4-(l-methyl)piperidinyl- methyl 2-phenylethyl 874 "(3,4- methylenedioxyphenyl)methyl" 2-phenylethyl 875 2-thienylmethyl 2-phenylethyl 876 4-biphenylmethyl 2-phenylethyl 877 pyrimidinylraethyl 2-phenylethyl 878 2-benzothiazolylmethyl 2-phenylethyl 879 2-benzothiophenylmethyl 2-phenylethyl 880 2-thiomethylethyl 2-phenylethyl 881 2-thiomethylmethyl 2-phenylethyl 882 2-methylpropyl 2-phenylethyl 883 2-methylbutyl 2-phenylethyl 884 3-methylbutyl 2-phenylethyl 885 cyclopropylmethyl 2-phenylethyl 886 cyclobutylmethyl 2-phenylethyl 887 cyclopentylmethyl 2-phenylethyl 888 p-hydroxyphenylmethyl 2-phenylethyl 889 p-nitrophenylmethyl 2-phenylethyl 890 p-aminophenylmethyl 2-phenylethyl 891 "4-(N,N- dimethylamino)phenylmethyl" 2-phenylethyl 892 benzyl 3-phenylpropyl 893 l-pyrolylmethyl 3-phenylpropyl 894 1-pyrazolylmethyl 3-phenylpropyl 895 l-imidazolylmethyl 3-phenylpropyl 896 l-indolylmethyl 3-phenylpropyl 897 l-triazolylmethyl 3-phenylpropyl 898 l-tetrazolylmethyl 3-phenylpropyl 899 2-pyridyLnethyl 3-phenylpropyl 900 3-pyridylmethyl 3-phenylpropyl 901 4-pyridylaethyl 3-phenylpropyl 902 cyclohexyl»ethyl 3-phenylpropyl 903 2-naphthylmethyl 3-phenylpropyl 904 3-naphthylmethyl 3-phenylpropyl 905 2-thiophenylmethyl 3-phenylpropyl 906 4-(l-methyl)piperidinyl- methyl 3-phenylpropyl 907 "(3,4- methylenedioxyphenyl)methyl" 3-phenylpropyl 908 2-thienylmethyl 3-phenylpropyl 909 4-biphenylmethy1 3-phenylpropyl 910 pyrimidinylmethyl 3-phenylpropyl 911 2-benzothiazolylmethyl 3-phenylpropyl 912 2-benzothiophenylmethyl 3-phenylpropyl 913 2-thiomethylethyl 3-phenylpropyl 914 2-thiomethylmethyl 3-phenylptopyl 915 2-methylpropyl 3-phenylpropyl 916 2-methylbutyl 3-phenylpropyl 89 LV 10096

Table 3 917 3-methylbutyl 3-phenylpropyl 918 cyclopropylmethyl 3-phenylpropyl 919 cyclobutylmethyl 3-phenylpropyl 920 cyclopentylroethyl 3-phenylpropyl 921 p-hydroxyphenylmethyl 3-phenylpropyl 922 p-nitrophenylmethyl 3-phenylpropyl 923 p-aminophenylroethyl 3-phenylpropyl 924 "4-(N,N- dimethylami.no) phenylmfethyl" 3-phenylpropyl 925 benzyl "2- (N, N-dimethylanu.no) ethyl" 926 l-pyrolylmethyl "2- (N, N-dinvethylanu.no) ethyl" 927 l-pyrazolylmethyl "2- (N,N-dinvethylamino)ethyl" 928 1 -imida zolylmethyl "2- (N,N-dimethylamino)ethyl" 929 l-indolylmethyl "2- (N, N-dinvethylanu.no) ethyl" 930 l-triazolylroethyl "2- (N, N-dinvethylanu.no) ethyl" 931 l-tetrazolylmethyl "2- (N,N-dinvethylanu.no) ethyl" 932 2-pyridylmethyl "2- (N, N-dinvethylanu.no) ethyl" 933 3-pyridylmethyl "2- (N, N-dinvethylanu.no) ethyl" 934 4-pyridylmethyl "2- (N,N-dimethylanu.no) ethyl" 935 cyclohexylmethyl "2- (N, N-dimethylanu.no) ethyl" 936 2-naphthylmethyl "2- (N,N-dimethylamino)ethyl" 937 3-naphthylmethyl "2-(N,N-dimethylamino)ethyl" 938 2-thiophenylmethyl "2- (N,N-dimethylanu.no) ethyl" 939 4-(l-methyl)piperidinyl-methyl "2- (N,N-dimethylanu.no) ethyļ" 940 "(3,4- methylenedioxyphehyl)methyl" "2- (N, N-dimethylanu.no) ethyl" 941 2-thienylroethyl "2- (N,N-dimethylanu.no) ethyl" 942 4-biphenylmethyl "2- (N, N-dimethylanu.no) ethyl" 943 pyrimidinylmethyl "2- (N,N-dinvethylamino)ethyl" 944 2-benzothiazolylmethyl "2-(N,N-dimethylamino)ethyl" 945 2-benzothiophenylmethyl "2- (N, N-dimethylanu.no) ethyl" 946 2-thiomethylethyl "2- (N, N-dimethylanu.no) ethyl" 947 2-thiomethylmethyl "2- (N, N-diroethylanu.no) ethyl" 948 2-methylpropyl "2-(N,N-dimethylamino)ethyl" 949 2-methylbutyl "2-(N,N-dimethylamino)ethyl" 950 3-methylbutyl "2- (N,N-dimethylanu.no) ethyl" 951 cyclopropylmethyl "2- (N, N-diroethylanu.no) ethyl" 952 cyclobutylmethy1 "2-(N,N-dimethylamino)ethyl" 953 cyclopentylmethyl "2-(N,N-dimethylamino)ethyl" 954 p-hydroxyphenylmethyl "2- (N, N-dimethylanu.no) ethyl" 955 p-nitrophenylmethyl "2-(N,N-dimethylamino)ethyl" 956 p-aminophenylmethyl "2-(N,N-dimethylamino)ethyl" 957 "4-(N,N- dimethylamino) phenylmethyl" "2-(N, N-dimethylamino)ethyl" 958 benzyl 3-oxetanylmethyl 959 l-pyrolylmethyl 3-oxetanylmethyl 960 l-pyrazolylmethyl 3-oxetanylmethyl 961 l-imidazolylmethyl 3-oxetanylmethyl 962 l-indolylmethyl 3-oxetanylroethyl 963 l-triazolylmethyl 3-oxetanylmethyl 964 l-tetrazolylmethyl 3-oxetanylmethyl 965 2-pyridylmethyl 3-oxetanylmethy1 966 3-pyridylmethyl 3-oxetanylmethyl 90 labie 3 967 4-pyridylmethyl 3-oxetanylmethyl 968 cyclohexylmethyl 3-oxetanylmethyl 969 2-naphthyljnethyl ' 3-oxetanylmethyl 970 3-naphthylmethyl 3-oxetanylmethyl 971 2-thiophenylnvethyl 3-oxetanylmethyl 972 4-(l-methyl)piperidinyl- methyl 3-oxetanylmethyl 973 "(3,4- methylenedioxyphenyl) methyl" 3-oxetanylmethyl 974 2-thienylmethyl 3-oxetanylmethyl 975 4-biphenylmethyl 3-oxetanylmethyl 976 pyrimidinylmethyl 3-©xetanylmethyl 977 2-benzothiaz61ylmethyl 3-oxetanylmethyl 978 2-ben zothiophenylmethyl 3-oxetanylir>ethyl 979 2-thiomethylethyl 3-oxetanylmethyl 980 2-thiornethylmethyl 3-oxetanylmethyl 981 2-methylpropyl 3-oxetanylmethyl 982 2-methylbutyl 3-oxetanylmethyl 983 3-methylbutyl 3-oxetanylmethyl 984 cyclopropylmethyl 3-oxetanylmethyl 985 cyclobutylmethyl 3-oxetanylmethyl 986 cyclopentylmethyl 3-oxetanylmethyl 987 p-hydroxyphenylmethyl 3-oxetanylmethyl 988 p-nitrophenylmethyl 3-oxetanylmethyl 989 p-aminophenylmethyl 3-oxetanylmethyl 990 "4-(N,N- dimethylami.no) phenylmethyl" 3-oxetanylmethyl 991 benzyl 2-tetrahydrofuranyl 992 l-pyrolylmethyl 2-tetrahydrofuranyl 993 l-pyrazolylmethyl 2-tetrahydrofuranyl 994 l-imidazolylmethyl 2-tetrahydrofuranyl 995 l-indolylmethyl 2-tetrahydrofuranyl 996 l-triazolylmethyl 2-tetrahydrofuranyl 997 1-tet ra zolylmethyl 2-tetrahydrofuranyl 998 2-pyridylmethyl 2-tetrahydrofuranyl 999 3-pyridylmethyl 2-tet rahydrofuranyl 1000 4-pyridylmethyl 2-tetrahydrofuranyl 1001 cyclohexylmethyl 2-tetrahydrofuranyl 1002 2-naphthylmethyl 2-tetrahydrofuranyl 1003 3-naphthylmethyl 2-tetrahydrofuranyl 1004 2-thiophenylmethyl 2-tetrahydrofuranyl 1005 4-(l-methyl)piperidinyl-methyl 2-tetrahydrofuranyl 1006 •(3,4- methylenedioxyphenyl)methyl" 2-tetrahydrofuranyl 1007 2-thienylmethyl 2-tetrahydrofuranyl 1008 4-biphenylmethyl 2-tetrahydrofuranyl 1009 pyrimidinylmethyl 2-tetrahydrofuranyl 1010 2-benzothiazolylmethyl 2-tetrahydrofuranyl 1011 2-benzothiophenylmethyl 2-tet rahydrofuranyl 1012 2-thiomethylethyl 2-tetrahydrofuranyl 1013 2-thiomethylmethyl 2-tetrahydrofuranyl 1014 2-methylpropyl 2-tetcahydrofuranyl 1015 2-methylbutyl 2-tetrahydrofuranyl

91LV

Iable-3 1016 3-methylbutyl 2-tetrahydrofuranyl 1017 cyclopropylmethyl 2-tetrahydro£uranyl 1018 cyclobutylmethyl 2-tetrahydro£uranyl 1019 cyclopentylmethyl 2-tetrahydrofuranyl 1020 '-hydroxyphenylmethyl 2-tetrahydrofuranyl 1021 p-nitrophenylmethyl 2-tetrahydrofuranyl 1022 p-aminophenylmethyl 2-tetrahydrofuranyl 1023 "4-(N,N- d imethylami.no) phenylmethyl" 2-tetrahydrofuranyl 1024 benzyl 2-methoxypropyl 1025 l-pyrolylmethyl 2-methoxyp ropy1 1026 l-pyrazolylmethyl 2-methoxypropyl 1027 l-imidazolylmethyl 2-methoxypropyl 1028 l-indolylmethyl 2-methoxypropyl 1029 l-triazolylmethyl 2-methoxypropyl 1030 l-tetrazolylmethyl 2-methoxypropyl 1031 2 -py r i dy lme t hy 1 2-methoxypropyl 1032 3-pyridylmethyl 2-methoxypropy1 1033 4-pyridylmethyl 2-methoxypropyl 1034 cyclohexylmethyl 2-methoxypropyl 1035 2-naphthylmethyl 2-methoxypropyl 1036 3-naphthylmethy1 2-methoxypropyl 1037 2-thiophenylmethyl 2-methoxypropyl 1038 4-(l-methyl)piperidinyl-methyl 2-methoxypropyl 1039 "(3,4- methylenedioxyphenyl) nvethyl" 2-methoxypropyl 1040 2-thienylmethyl 2-methoxypropyl 1041 4-biphenylmethyl 2-methoxypropyl 1042 pyrimidinylmethyl 2-methoxypropyl 1043 2-benzothiazolylnvethyl 2-methoxypropyl 1044 2-benzothiophenylmethyl 2-methoxypropyl 1045 2-thiomethylethyl 2-methoxypropyl 1046 2-thiomethylmethyl 2-methoxypropyl 1047 2-methylpropyl 2-methoxypropyl 1048 2-methylbutyl 2-methoxypropyl 1049 3-methylbutyl 2-methoxypropyl 1050 cyclopropylmethyl 2-methoxypropyl 1051 cyclobutylmethyl 2-methoxypropyl 1052 cyc1openty lmethy1 2-methoxypropyl 1053 p-hydroxyphenylmethyl 2-methoxypropyl 1054 p-nitrophenylmethyl 2-methoxypropyl 1055 p-aminophenylmethyl 2-methoxypropyl 1056 "4-(N,N- dimethylamino) phenylmethyl" 2-methoxypropyl 1057 benzyl 2-ethoxyethyl 1058 l-pyrolylmethyl 2-ethoxyethyl 1059 1-pyrazolylmethyl 2-ethoxyethyl 1060 l-imidazolylmethyl 2-ethoxyethyl 1061 l-indolylmethyl 2-ethoxyethyl 1062 l-triazolylmethyl 2-ethoxyethyl 1063 l-tetrazolylmethyl 2-ethoxyethyl 1064 2-pyridylmethyl 2-ethoxyethyl 1065 3-pyrldylmethyl 2-ethoxyethyl 92

Tabl£-1 1066 4-pyridylmethyl 2-ethoxyethyl 1067 cyclohexyl»ethyl 2-ethoxyethyl 1068 2-naphthylmethyl. 2-ethoxyethyl 1069 3-naphthyljnethyl 2-ethoxyethyl 1070 2-thiophenylmethyl 2-ethoxyethyl 1071 4 - (l-methyl) piperidinyl-methyl 2-ethoxyethyl 1072 "(3,4- met hylenedioxyphenyl) methyl" 2-ethoxyethyl 1073 2-thienylioethyl 2-ethoxyethyl 1074 4-biphenylmethyl 2-ethoxyethyl 1075 pyrimidinylmethyl 2-ethoxyethyl 1076 2-benzothiaz,olyln»ethyl 2-ethoxyethyl 1077 2-benzothiophenylmethyl 2-ethoxyethyl 1078 2-thiomethylethyl 2-ethoxyethyl 1079 2-thiomethylmethyl 2-ethoxyethyl 1080 2-methylpropyl 2-ethoxyethyl 1081 2-methylbutyl 2-ethoxyethyl 1082 3-methylbutyl 2-ethoxyethyl 1083 cyclopropylmethyl 2-ethoxyethyl 1084 . cyclobutylJn€thyl 2-ethoxyethyl 1085 cyclopentylmethyl 2-ethoxyethyl 1086 p-hydroxyphenylmethyl 2-ethoxyethyl 1087 p-nitrophenylmethyl 2-ethoxyethyl 1088 p-aminophenylmethyl 2-ethoxyethyl 1089 "4-(N,N- diinethylamino) phenylmethyl" 2-ethoxyethyl 1090 benzyl 2-(l-pyrolyl)ethyl 1091 l-pyrolylmethyl 2-(l-pyrolyl)ethyl 1092 1-pyrazolylmethyl 2-(l-pyrolyl)ethyl 1093 1 - imi da z o ly lme t hy 1 2-(l-pyrolyl)ethyl 1094 1-indolylmethyl 2-(l-pyrolyl)ethyl 1095 l-triazolylmethyl 2-(l-pyrolyl)ethyl 1096 1-tetrazolylmethyl 2-(l-pyrolyl)ethyl 1097 2-pyridylmethyl 2-(l-pyrolyl)ethyl 1098 3-pyridylmethyl 2-(l-pyrolyl)ethyl 1099 4-pyridylmethyl 2-(l-pyrolyl)ethyl 1100 cyclohexylmethyl 2-(l-pyrolyl)ethyl 1101 2-naphthylmethyl 2-(l-pyrolyl)ethyl 1102 3-naphthylmethyl 2-(l-pyrolyl)ethyl 1103 2-thiophenylmethyl 2-(l-pyrolyl)ethyl 1104 4- (l-jnethyl)piperidinyl-methyl 2-(l-pyrolyl)ethyl 1105 "(3,4- methylenedioxyphenyl) methyl" 2-(l-pyrolyl)ethyl 1106 2-thienylmethyl 2-(l-pyrolyl)ethyl 1107 4-biphenyljnethyl 2-(l-pyrolyl)ethyl 1108 pyrimidinylnvethyl 2-(l-pyrolyl)ethyl 1109 2-benzothiazolylmethyl 2-(l-pyrolyl)ethyl 1110 2-benzothiophenylmethyl 2-(l-pyrolyl)ethyl 1111 2-thiomethylethyl 2-(l-pyrolyl)ethyl 1112 2-thlomethylmethyl 2-(l-pyrolyl)ethyl 1113 2-methylpropyl 2-(l-pyrolyl)ethyl 1114 2-methylbutyl 2-(l-pyrolyl)ethyl 93 LV 10096 labie-2 1115 3-methylbutyl 2-(l~pyrolyl)ethyl 1116 cyclopropylJnethyl 2-(l-pyrolyl)ethyl 1117 cyclobutylnvethyl 2-(l-pyrolyl)ethyl 1118 cyclopentylmethyl 2-(l-pyrolyl)ethyl 1119 p-hydroxyphenylmethyl 2-(l-pyrolyl)ethyl 1120 p-nitrophenylmethyl 2-(l-pyrolyl)ethyl 1121 p-aminophenylmethyl 2-(l-pyrolyl)ethyl 1122 "4-(N,N- diroethylami.no) phenylmethyl" 2- (l-pyrolyl)ethyl 1123 benzyl 2-(l-iroidazolyl)ethyl 1124 l-pyrolylmethyl 2-(l-imidazolyl)ethyl 1125 l-pyrazolylmethyl 2-(l-imidazolyl)ethyl 1126 l-imidazolylmethyl 2-{l-imidazolyl)ethyl 1127 l-indolylmethyl 2-(l-imidazolyl)ethyl 1128 l-triazolylmethyl 2-(l-imidazolyl)ethyl 1129 l-tetrazolylmethyl 2-(l-imidazolyl)ethyl 1130 2-pyridylmethyl 2-(l-imidazolyl)ethyl 1131 3-pyridylmethyl 2-(l-imidazolyl)ethyl 1132 4-pyridylmethy1 2-(l-imidazolyl)ethyl 1133 cyclohexylmethyl 2-(l-iroidazolyl)ethyl 1134 2-naphthylmethy1 2-(l-imidazolyl)ethyl 1135 3-naphthylmethyl 2-(l-imidazolyl)ethyl 1136 2-thiophenylmethyl 2-(l-imidazolyl)ethyl 1137 4-(l-methyl)piperidinyl-methyl 2-(l-imidazolyl)ethyl 1138 "(3,4- methylenedioxyphenyl)methyl" 2-(l-imidazolyl)ethyl 1139 2-thienylmethyl 2-(l-imidazolyl)ethyl 1140 4-biphenylmethyl 2-(l-imidazolyl)ethyl 1141 pyriroi diny lmethy1 2-(l-imidazolyl)ethyl 1142 2-benzothiazolylroethyl 2-(l-imidazolyl)ethyl 1143 2-benzothiophenylmethyl 2-(l-imidazolyl)ethyl 1144 2-thiomethylethyl 2-(l-imidazolyl)ethyl 1145 2-thiomethylmethyl 2-(l-imidazolyl)ethyl 1146 2-methylpropyl 2-(l-imidazolyl)ethyl 1147 2-methylbutyl 2-(l-imidazolyl)ethyl 1148 3-methylbutyl 2-(l-imidazolyl)ethyl 1149 cyclopropylmethyl 2-(l-imidazolyl)ethyl 1150 cyclobutylmethyl 2-(l-iroidazolyl)ethyl 1151 cyclopentylmethyl 2-(l-imidazolyl)ethyl 1152 p-hydroxyphenylmethyl 2-(l-imidazolyl)ethyl 1153 p-nitrophenylmethyl 2-(l-imidazolyl)ethyl 1154 p-andnophenylroethyl 2-(l-imidazolyl)ethyl 1155 "4-(N,N- dimethylamino)phenylmethyl" 2-(l-iroidazolyl)ethyl 1156 benzyl 2-pyridylmethyl 1157 l-pyrolylmethyl 2-pyridylrnethyl 1158 l-pyrazolylmethyl 2-pyridylmethyl 1159 l-imidazolylmethyl 2-pyridylmethyl 1160 l-indolylmethyl 2-pyridylmethyl 1161 l-triazolylmethyl 2-pyridylmethyl 1162 l-tetrazolylmethyl 2-pyridylmethyl 1163 2-pyridylmethyl 2-pyridylmethyl 1164 3-pyridylmethyl 2-pyridylmethyl 94 labie 3 1165 4-pyridylmethyl 2-pyridylmethyl 1166 cyclohexylmethyl 2-pyridylmethyl 1167 2-naphthylmethyl 2-pyridylmethyl 1168 3-naphthylmethyl 2-pyridylmethyl 1169 2-thiophenylmethyl 2-pyridylmethyl 1170 4-{l-methyl)piperidinyl- methyl 2-pyridylmethyl 1171 "(3,4- methylenedioxyphenyl)methyl" 2-pyridylmethyl 1172 2-thienylroethyl 2-pyridylmethyl 1173 4-biphenylmethyl 2-pyridylmethyl 1174 pyrimidinylmethyl 2-pyridylmethyl 1175 2-benzothiazolylmethyl 2-pyridylmethyl 1176 2-benzothiophenylmethyl 2-pyridylmethyl 1177 2-thiomethylethyl 2-pyridylmethyl 1178 2-thiomethylmethyl 2-pyridylmethyl 1179 2-methylpropyl 2-pyridylmethyl 1180 2-methylbutyl 2-pyridylmethyl 1181 3-methylbutyl 2-pyridylmethyl 1182 cyclopropylmethyl 2-pyridylmethyl 1183 cyclobutylmethyl 2-pyridylmethyl 1184 cyclopentylmethyl 2-pyridylmethyl 1185 p-hydroxyphenylmethyl 2-pyridylmethyl 1186 p-nitrophenylmethyl 2-pyridylmethyl 1187 p-aminophenylwethyl 2-pyridylmethyl 1188 "4-(N,N- dimethylami.no) phenylmethyl" 2-pyridylmetnyl 1189 benzyl 2-thiomethylethyl 1190 l-pyrolylmethyl 2-thiomethylethyl 1191 l-pyrazolylmethyl 2-thiomethylethyl 1192 l-imidazolylmethyl 2-thiomethylethyl 1193 l-indolylmethyl 2-thiomethylethyl 1194 l-triazolylmethyl 2-thiomethylethyl 1195 l-tetrazolylmethyl 2-thiomethylethyl 1196 2-pyridylmethyl 2-thiomethylethyl 1197 3-pyridylmethyl 2-thiomethylethyl 1198 4-pyridylmethyl 2-thiomethylethyl 1199 cyclohexylmethyl 2-thiomethylethyl 1200 2-naphthylmethyl 2-thiomethylethyl 1201 3-naphthylmethyl 2-thiomethylethyl 1202 2-thiophenylmethyl 2-thiomethylethyl 1203 4- (l-methyl)piperidinyl-methyl 2-thiomethylethyl 1204 "(3,4- methylenedioxyphenyl) methyl* 2-thiomethylethyl 1205 2-thienylmethyl 2-thiomethylethyl 1206 4-biphenylmethyl 2-thiomethylethyl 1207 pyrimidinylmethyl 2-thiomethylethyl 1208 2-benzothiazolylmethyl 2-thiomethylethyl 1209 2-benzothiophenylmethyl 2-thiomethylethyl 1210 2-thiomethylethyl 2-thiomethylethyl 1211 2-thiomethylmethyl 2-thiomethylethyl 1212 2-methylpropyl 2-thiomethylethyl 1213 2-methylbutyl 2-thiomethylethyl 95 LV 10096

Table 3 1214 3-methylbutyl 2-thiomethylethyl 1215 cyclopropylmethyl 2-thiomethylethyl 1216 cyclobutylmethyl 2-thiomethylethyl 1217 cyclopentylmethyl 2-thiomethylethyl 1218 p-hydroxyphenylmethyl 2-thiomethylethyl 1219 p-nitrophenylmethyl 2-thiomethylethyl 1220 p-aminophenylmethyl 2-thiomethylethyl 1221 •4-(N,N- 2-thiomethylethyl dimethylami.no) phenylmethyl" 96

Tablfi-A TABLE 4 0 \

N

NH r22

Exampl,a Number R4 - R7 a22 1222 benzyl allyl 1223 l-pyrolyljnethyl allyl 1224 l-pyrazolylmethyl allyl 1225 l-imidazolylmethyl allyl 1226 l-indolylmethyl allyl 1227 l-triazolylmethyl allyl 1228 l-tetrazolylmethyl allyl 1229 2-pyridylaethyl allyl 1230 3-pyridylmethyl allyl 1231 4-pyridylmethyl allyl 1232 cyclohexylmethyl allyl 1233 2-naphthylmethyl allyl 1234 3-naphthylmethyl allyl 1235 2-thiophenyljnethyl allyl 1236 4- (l-methyl)piperidinyl-methyl allyl 1237 "(3,4- methylenedioxyphenyl) methyl" allyl 1238 2-thienylmethyl allyl 1239 4-biphenylmethyl allyl 1240 pyr iitddinylmethy 1 allyl 1241 2-benzothia zo ly lmethy 1 allyl 1242 2-benzothiophenylmethyl allyl 1243 2-thiomethylethyl allyl 1244 2-thioroethylmethyl allyl 1245 2-methylpropyl allyl 1246 2-methylbutyl allyl 1247 3-methylbutyl allyl 1248 cyclopropyljnethyl allyl 1249 cyclobutylmethyl allyl 1250 cyclopentylmethyl allyl 97 97LV 10096 labie ...1 1251 p-hydroxyphenylmethyl allyl 1252 p-nitropheny]jnethyl allyl 1253 p-aminophenylmethyl allyl 1254 "4-(N,N- dimethylami.no) phenylmethyl" allyl 1255 benzyl propyl 1256 l-pyrolylmethyl propyl 1257 l-pyrazolylmethyl propyl 1258 l-imidazolylmethyl propyl 1259 l-indolylmethyl propyl 1260 l-triazolylmethyl propyl 1261 l-tetrazolylmethyl propyl 1262 2-pyridylmethyl propyl 1263 3-pyridylmethyl propyl 1264 4-pyridylmethyl propyl 1265 cyclohexylmethyl propyl 1266 2-naphthylmethyl propyl 1267 3-naphthylmethyl propyl 1268 2-thiophenylroethyl propyl 1269 4- (l-methyl)piperidinyl-methyl propyl 1270 *(3# 4- methylenedioxyphenyl) methyl" propyl 1271 2-thienylmethyl propyl 1272 4-biphenylmethyl propyl 1273 pyrimidinylmethyl propyl 1274 2-benzothiazolylmethyl propyl 1275 2-benzothiophenylinethyl propyl 1276 2-thiomethylethyl propyl 1277 2-thiomethylmethyl propyl 1278 2-methylpropyl propyl 1279 2-methylbutyl propyl 1280 3-methylbutyl propyl 1281 cyclopropylmethyl propyl 1282 cyclobutylmethyl propyl 1283 cyclopentylmethyl propyl 1284 p-hydroxyphenylmethyl propyl 1285 p-nitrophenylmethyl propyl 1286 p-aminophenylmethyl propyl 1287 4-(N,N- dimethylamino) phenylmethyl" propyl 1288 benzyl n-butyl 1289 l-pyrolylmethyl n-butyl 1290 l-pyrazolylmethyl n-butyl 1291 l-imidazolylmethyl n-butyl 1292 l-indolylmethyl n-butyl 1293 l-ttiazolylmethyl n-butyl 1294 l-tetrazolylmethyl n-butyl 1295 2-pyridylmethyl n-butyl 1296 3-pyrldylinethyl n-butyl 1297 4-pyridylmethyl n-butyl 1298 cyclohexylmethyl n-butyl 1299 2-naphthylmethyl n-butyl 1300 3-naphthylmethyl n-butyl 1301 2-thiophenylmethyl n-butyl 1302 4-(l-methyl)piperidinyl- methyl n-butyl 98

Table 4 1303 •<3,4- methylenedioxyphenyl)methyl" n-butyl 1304 2-thienylmethyl n-butyl 1305 4-biphenylmethyl n-butyl 1306 pyrimidinylmethyl n-butyl 1307 2-benzothiazolylmethyl n-butyl 1308 2-benzothiophenylmethyl n-butyl 1309 2-thiomethylethyl n-butyl 1310 2-thiomethylmethyl n-butyl 1311 2-methylpropyl n-butyl 1312 2-methylbutyl n-butyl 1313 3-methylbutyl n-butyl 1314 cyclopropylxiethyl n-butyl 1315 cyclobutylmethyl n-butyl 1316 cyclopentylmethyl n-butyl 1317 p-hydroxyphenylmethyl n-butyl 1318 p-nitrophenylmethyl n-butyl 1319 p-aminophenylmethyl n-butyl 1320 "4-(N,N- dimethylami.no) phenylmethyl" n-butyl 1321 benzyl isobutyl 1322 l-pyrolylmethyl isobutyl 1323 l-pyrazolylmethyl isobutyl 1324 l-imidazolylmethyl isobutyl 1325 l-indolylmethyl isobutyl 1326 l-triazolylmethyl iaobutyl 1327 l-tetrazolylmethyl isobutyl 1328 2-pyridylmethyl isobutyl 1329 3-pyridylmethyl isobutyl 1330 4-pyridylmethyl isobutyl 1331 cyclohexylmethyl isobutyl 1332 2-naphthylmethyl isobutyl 1333 3-naphthylmethyl iaobutyl 1334 2-thiophenylmethyl iaobutyl 1335 4- (l-methyl)piperidinyl-methyl iaobutyl 1336 "(3,4- methylenedioxyphenyl)methyl" isobutyl 1337 2-thienylmethyl iaobutyl 1338 4-biphenylmethyl isobutyl 1339 pyrimidinylmethyl isobutyl 1340 2-benzothiazolylmethyl iaobutyl 1341 2-benzothiophenylmethyl iaobutyl 1342 2-thiomethylethyl iaobutyl 1343 2-thiomethylroethyl isobutyl 1344 2-methylpropyl isobutyl 1345 2-methylbutyl isobutyl 1346 3-methylbutyl isobutyl 1347 cyclopropylmethyl isobutyl 1348 cyclobutylmethyl iaobutyl 1349 cyclopentylmethyl isobutyl 1350 p-hydroxyphenylraethyl isobutyl 1351 p-nitrophenylmethyl isobutyl 1352 p-aminophenylmethyl isobutyl 1353 "4-(N,N- dimethylamino) phenylmethyl* isobutyl 1354 benzyl 2-butyl 99LV 10096

Table 4 1355 l-pyrolylinethyl 2-butyl 1356 l-pyrazolylmethyl 2-butyl 1357 l-imdazolylmethyl 2-butyl 1358 l-indolylmethyl 2-butyl 1359 l-triazolylmethyl 2-butyl 1360 l-tetrazolylmethyl 2-butyl 1361 2-pyridylxnethyl 2-butyl' 1362 3-pyridylmethyl 2-butyl 1363 4-pyridylmethyl 2-butyl 1364 cyclohexylinethyl 2-butyl 1365 2-naphthylmethyl 2-butyl 1366 3 -naphthyljnethyl 2-butyl 1367 2-thiophenylmethyl 2-butyl 1368 4-(l-methyl)piperidinyl- methyl 2-butyl 1369 "(3,4- methylenedioxyphenyl)methyl" 2-butyl 1370 2-thienylmethyl 2-butyl 1371 4-biphenylmethyl 2-butyl 1372 pyriid.dinylinet.hyl 2-butyl 1373 2-benzothiazolylmethyl 2-butyl 1374 2-benzothiophenylmethyl 2-butyl 1375 2-thiomethylethyl 2-butyl 1376 2-thioroethylmethyl 2-butyl 1377 2-methylpropyl 2-butyl 1378 2-nvethylbutyl 2-butyl 1379 3-methylbutyl 2-butyl 1380 cyclopropylmethyl 2-butyl 1381 cyclobutyLnethyl 2-butyl 1382 cyclopentylmethyl 2-butyl 1383 p-hydroxyphenylmethyl 2-butyl 1384 p-nit rophenylmethyl 2-butyl 1385 p-aminophenylmethyl 2-butyl 1386 "4-(N,N- dimethylamino)phenylmethyl" 2-butyl 1387 benzyl "3, 3-dimethallyl 1388 l-pyrolylmethyl *3,3-dimethallyl 1389 l-pyrazolylmethyl *3,3-dimethallyl 1390 1-imida zolylmethyl "3, 3-dimethallyl 1391 l-indolylmethyl *3,3-dimethallyl 1392 l-triazolylinethyl "3,3-dimethallyl 1393 1-tetra zolylmethyl "3,3-dimethallyl 1394 2-pyridylmethyl *3,3-dimethallyl 1395 3-pyridylmethyl "3, 3-dimethallyl 1396 4-pyridylroethyl "3,3-dimethallyl' 1397 cyclohexylmethyl "3,3-dimethallyl' 1398 2-naphthylmethyl "3,3-dimethallyl' 1399 3-naphthylmethyl "3,3-dimethallyl' 1400 2-thiophenylmethyl "3,3-dimethallyl' 1401 4-(l-methyl)piperidinyl-methyl *3, 3-dimethallyl' 1402 "(3,4- methylenedioxyphenyl)methyl" "3,3-dimethallyl' 1403 2-thienylmethyl "3,3-dimethallyl' 1404 4-biphenylmethyl "3,3-dimethallyl' 1405 pyrimldinylmethyl "3,3-dimethallyl' 1406 2-benzothiazolylmethyl 3,3-dimethallyl' 100 100 Tablfi-J. 1407 2-benzothiophenylmethyl 1408 2-thiomethylethyl 1409 2-thiomethylmethyl 1410 2-nvethylpropyl 1411 2-methylbutyl 1412 3-methylbutyl 1413 cyclopropylxnethyl 1414 cyclobutylmethyl 1415 cyclopentylmethyl 1416 p-hydroxyphenylmethyl 1417 p-nitrophenylmethyl 1418 p-aminophenylmethyl 1419 "4-(N,N- dimethylami.no) phenylmethyl" 1420 benzyl 1421 l-pyrolylmethyl 1422 l-pyrazolylmethyl 1423 l-imidazolylmethyl 1424 l-indolylmethyl 1425 l-tria2olylmethyl 1426 l-tetrazolylmethyl 1427 2-pyridylmethyl 1428 3-pyridylmethyl 1429 4-pyridylmethyl 1430 cyclohexylmethyl 1431 2-naphthylmethyl 1432 3-naphthylmethyl 1433 2-thiophenylmethyl 1434 4-(l-methyl)piperidinyl-methyl 1435 "(3,4- methylenedioxyphenyl)methyl 1436 2-thienylroethyl 1437 4-biphenylmethyl 1438 pyrimidinylmethyl 1439 2-benzothiazolylmethyl 1440 2-benzothiophenylmethyl 1441 2-thiomethylethyl 1442 2-thiomethylmethyl 1443 2-methylpropyl 1444 2-methylbutyl 1445 3-methylbutyl 1446 cyclopropylmethyl 1447 cyclobutylmethyl 1448 cyclopentylmethyl 1449 p-hydroxyphenylmethyl 1450 p-nitrophenylmethyl 1451 p-aminophenylroethyl 1452 "4-(N,N- dimethylamino)phenylmethyl" 1453 benzyl 1454 l-pyrolylmethyl 1455 l-pyrazolylmethyl 1456 l-imidazolylmethyl 1457 l-indolylmethyl 1458 l-triazolylmethyl 1459 l-tetrazolylmethyl "3,3-diroethallyl" "3/3-dimethallyl" *3,3-dimethallyl" "3,3-diwethallyl" "3, 3-diinethallyl" 3,3-dimethallyl" •3,3-dimethallyl" "3/3-dimethallyl" "3,3-dimethallyl" 3i 3-dimethallyl" •3/3-dimethallyl" 3,3-dimethallyl" "3i 3-dimethallyl" 3-methallyl 3-roethallyl 3-oethallyl 3-oethallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-roethallyl 3-»ethallyl 3-methallyl 3-roethallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-roethallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-jnethallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 3-methallyl 2-methallyl 2-methallyl 2-methallyl 2-methallyl 2-methallyl 2-methallyl 2-methallyl 101 LV 10096 labie._& 1460 2-pyridylmethyl 2-methallyl 1461 3-pyridylmethyl 2-methallyl 1462 4-pyridylmethyl 2-methallyl 1463 cyclohexyljnethyl 2-methallyl 1464 2-naphthylmethyl 2-methallyl 146S 3-naphthylmethyl 2-methallyl 1466 2-thiophenylmethyl 2-methallyl 1467 · 4-{l-methyl)piperidinyl- methyl 2-methallyl 1468 "(3,4- jnethylenedioxyphenyl)methyļ'· 2-methallyl 1469 2-thienyImethyl 2-methallyl 1470 4-biphenylinethyl 2-methallyl 1471 pyrimidinylmethyl 2-methallyl 1472 2-benzothiazolylmethyl 2-methallyl 1473 2-benzothiophenylmethyl 2-methallyl 1474 2-thiomethylethyl 2-methallyl 1475 2-thiomethyljnethyl 2-methallyl 1476 2-methylpropyl 2-methallyl 1477 2-methylbutyl 2-methallyl 1478 3-methylbutyl 2-methallyl 1479 cyclopropylmethyl 2-methallyl 1480 cyclobutylmethyl 2-methallyl 1481 cyclopentylmethyl 2-methallyl 1482 p-hydroxyphenylmethyl 2-methallyl 1483 p-nit r ophenylmethyl 2-methallyl 1484 p-aminophenyljnethyl 2-methallyl 1485 "4-(N,N- dimethylami.no) phenylmethyl" 2-methallyl 1486 benzyl 2-propyl 1487 l-pyrolylmethyl 2-propyl 1488 l-pyrazolylmethyl 2-propyl 1489 l-imidazolylmethyl 2-propyl 1490 l-indolylmethyl 2-propyl 1491 l-triazolylmethyl 2-propyl 1492 1 -1 e t ra z o ly lme t hyl 2-propyl 1493 2-pyridylmethyl 2-propyl 1494 3-pyridylmethyl 2-propyl 1495 4-pyridylmethyl 2-propyl 1496 cyclohexylmethyl 2-propyl 1497 2-naphthylmethyl 2-propyl 1498 3-naphthylmethyl 2-propyl 1499 2-thiophenylmethyl 2-propyl 1500 4- (l-methyl) piperidinyl-methyl 2-propyl 1501 "(3,4- methylenedioxyphenyl) methyl" 2-propyl 1502 2-thienylmethyl 2-propyl 1503 4-biphenylraethyl 2-propyl 1504 pyrimidinylroethyl 2-propyl 1505 2-benzothiazolylmethyl 2-propyl 1506 2 -benzothiopheny lmethyl 2-propyl 1507 2-thiomethylethyl 2-propyl 1508 2-thiomethylmethyl 2-propyl 1509 2-methylpropyl 2-propyl 1510 . 2-methylbutyl 2-propyl 1511 3-methylbutyl 2-propyl 102

Tablg-3. 1512 cyclopropylffiethyl 2-propyl 1513 cyclobutylmethyl 2-propyl 1514 cyclopentylmethyl 2-propyl 1515 p-hydroxyphenylmethyl 2-propyl 1516 p-nitrophenylmethyl 2-propyl 1517 p-aminophenylmethyl 2-propyl 1518 "4-(N,N- dimethylami.no) phenylroethyl" 2-propyl 1519 benzyl cyclopropyl 1520 l-pyrolylmethyl cyclopropyl 1521 1-pyrazolylmethyl cyclopropyl 1522 1-imida zolylmethyl cyclopropyl 1523 l-indolylroethyl cyclopropyl 1524 l-triazolylmethyl cyclopropyl 1525 1-tetra2olylmethyl cyclopropyl 1526 2-pyridylmethyl cyclopropyl 1527 3-pyridylmethyl cyclopropyl 1528 4-pyridylmethyl cyclopropyl 1529 cyclohexylmethyl cyclopropyl 1530 2-naphthylmethyl cyclopropyl 1531 3-naphthylmethyl cyclopropyl 1532 2-thiophenylmethyl cyclopropyl 1533 4- (l-methyl)piperidinyl-methyl cyclopropyl 1534 " (3,4- methylenedioxyphenyl) methyl" cyclopropyl 1535 2-thienylmethyl cyclopropyl 1536 4-biphenylmethyl cyclopropyl 1537 pyrimidinylmethyl cyclopropyl 1538 2-benzothiazolylmethyl cyclopropyl 1539 2-benzothiophenylmethyl cyclopropyl 1540 2-thiomethylethyl cyclopropyl 1541 2-thiomethylmethyl cyclopropyl 1542 2-methylpropyl cyclopropyl 1543 2-methylbutyl cyclopropyl 1544 3-methylbutyl cyclopropyl 1545 cyclopropylmethyl cyclopropyl 1546 cyclobutylmethyl cyclopropyl 1547 cyclopentylmethyl cyclopropyl 1548 p-hydroxyphenylmethyl cyclopropyl 1549 p-nitrophenylmethyl cyclopropyl 1550 p-aminophenylmethyl cyclopropyl 1551 "4-{N,N- dimethylamino) phenylmethyl" cyclopropyl 1552 benzyl cyclopropylmethyl 1553 l-pyrolylmethyl cyclopropylmethyl 1554 l-pyrazolylmethyl cyclopropylmethyl 1555 1-imida z olylmethyl cyclopropylmethyl 1556 l-indolylmethyl cyclopropylmethyl 1557 1-triazolylmethyl cyclopropylmethyl 1558 1-tetrazolylmethyl cyclopropylmethyl 1559 2-pyridylroethyl cy c lop ro'py lmethyl 1560 3-pyridylraethyl cyc1opropylmethyl 1561 4-pyridylmethyl cyc lopropy lmethyl 1562 cyclohexylmethyl cyclopropylmethyl 1563 2-naphthylmethyl cyc1op ropylmethy1 1564 3-naphthylmethyl cyclopropylmethyl 103 LV 10096

Table 4. 1565 2-thiophenylmethyl cyclopropylmethyl 1566 4-(l-methyl)piperidinyl-methyl cyclopropylmethyl 1567 "(3,4- methylenedioxyphenyl)methyl" cyclopropylmethyl 1568 2-thienylmethyl cyclopropylmethyl 1569 4-biphenylmethyl cyclopropylmethyl 1570 pyrimidinylmethyl cyclopropylmethyl 1571 2-benzothiazolylmethyl cyclopropylmethyl 1572 2-benzothiophenylmethyl cyclopropylmethyl 1573 2-thiomethylethyl cyclopropylmethyl 1574 2-thiomethylmethyl cyclopropylmethyl 1575 2-methylpropyl cyclopropylmethyl 1576 2-methylbutyl cyclopropylmethyl 1577 3-methylbutyl cyclopropylmethyl 1578 cyc1opropylmethy1 cyclopropylmethyl 1579 cyclobutylmethyl cyclopropylmethyl 1580 cyclopentylmethyl cyclopropylmethyl 1581 p-hydroxyphenylmethyl cyclopropylxnethyl 1582 p-nitrophenylmethyl cyclopropylmethyl 1583 p-aminophenylmethyl cyclopropylmethyl 1584 "4-(N,N- dimethylami.no) phenylmethyl" cyclopropylmethyl 1585 benzyl n-pentyl 1586 l-pyrolylmethyl n-pentyl 1587 l-pyrazolylmethyl n-pentyl 1588 1-imidazο1ylmethy1 n-pentyl 1589 l-indolylmethyl n-pentyl 1590 l-triazolylmethyl n-pentyl 1591 1-tetrazolylmethyl n-pentyl 1592 2-pyridylmethyl n-pentyl 1593 3-pyridylmethyl n-pentyl 1594 4-pyridylmethyl n-pentyl 1595 cyclohexylmethyl n-pentyl 1596 2-naphthylmethy1 n-pentyl 1597 3-naphthylmethyl n-pentyl 1598 2-thiophenylmethyl n-pentyl 1599 4-(l-methyl)piperidinyl-methyl n-pentyl 1600 "(3,4- methylenedioxyphenyl)methyl" n-pentyl 1601 2-thienylmethyl n-pentyl 1602 4-biphenylmethyl n-pentyl 1603 pyrimidinylmethyl n-pentyl 1604 2-benzothiazolylmethyl n-pentyl 1605 2-benzothiophenylmethyl n-pentyl 1606 2-thiomethylethyl n-pentyl 1607 2-thiomethylmethyl n-pentyl 1608 2-methylpropyl n-pentyl 1609 2-methylbutyl n-pentyl 1610 3-methylbutyl n-pentyl 1611 cyclopropylmethyl n-pentyl 1612 cyclobutylmethyl n-pentyl 1613 cyclopentylmethyl n-pentyl 1614 p-hydroxyphenylmethyl n-pentyl 1615 p-nitrophenylmethyl n-pentyl 1616 p-aminophenylmethyl n-pentyl 104

Table 4 1617 •4-(N,N- dimethylamino)'phenylmethyl" n-pentyl 1618 benzyl 2-pentyl 1619 l-pyrolylmethyl 2-pentyl 1620 l-pyrazolylmethyl 2-pentyl 1621 1 - imida z o ly lxne thyl 2-pentyl 1622 l-indolylroethyl 2-pentyl 1623 l-triazolylmethyl 2-pentyl 1624 l-tetrazolylmethyl 2-pentyl 1625 2-pyridylroethy1 2-pentyl 1626 3-pyridylmethyl 2-pentyl 1627 4-pyridyliaethyl 2-pentyl 1628 cyclohexylmethyl 2-pentyl 1629 2-naphthylmethyl 2-pentyl 1630 3 -naphthy lmethy 1 2-pentyl 1631 2-thiophenylmethyl 2-pentyl 1632 4- (l-methyl) piperidinyl-methyl 2-pentyl 1633 "(3,4- methylenedioxyphenyl) methyl" 2-pentyl 1634 2-thienylroethyl 2-pentyl 1635 4-biphenylmethyl 2-pentyl 1636 py r imi d i ny lme t hy 1 2-pentyl 1637 2-benzothiazolylmethyl 2-pentyl 1638 2-benzothiophenylmethyl 2-pentyl 1639 2-thiomethylethyl 2-pentyl 1640 2-thiomethylmethyl 2-pentyl 1641 2-methylpropyl 2-pentyl 1642 2-methylbutyl 2-pentyl 1643 3-methylbutyl 2-pentyl 1644 cyclopropylmethyl 2-pentyl 1645 cyclobutylmethyl 2-pentyl 1646 cyclopentylmethyl 2-p«ntyl 1647 p-hydroxyphenylmethyl 2-pentyl 1648 p-nitrophenylmethyl 2-pentyl 1649 p-aminophenylmethyl 2-pentyl 1650 "4-(N,N- dimethylami.no) phenylmethyl" 2-pentyl 1651 benzyl 3-pentyl 1652 l-pyrolylmethyl 3-pentyl 1653 l-pyrazolylmethyl 3-pentyl 1654 l-imidazolylmethyl 3-pentyl 1655 l-indolylmethyl 3-pentyl 1656 l-triazolylmethyl 3-pentyl 1657 l-tetrazolylmethyl 3-pentyl 1658 2 -pyridy lmethy 1 3-pentyl 1659 3-pyridylmethyl 3-pentyl 1660 4 -pyridylme thyl 3-pentyl 1661 cyclohexylmethyl 3-pentyl 1662 2-naphthylmethyl 3-pentyl 1663 3 -naphthylmethy 1 3-pentyl 1664 2 -th iopheny lmethyl 3-pentyl 1665 4— (1 -methyl)piperidinyl-tnethyl 3-pentyl 1666 "(3,4- methylenedioxyphenyl) methyl" 3-pentyl 1667 2 -thieny lmethy 1 3-pentyl 105 105 Table .4 1668 4-biphenylmethyl 1669 pyriml dinylmethy1 1670 2-benzothiazolylmethyl 1671 2-benzothiophenylmethyl 1672 2-thiomethylethyl 1673 2-thiomethylmethyl 1674 2-methylpropyl 1675 2-methylbutyl 1676 3-nvethylbutyl 1677 cyclopropylmethyl 1678 cyclobutylinethyl 1679 cyclopentylmethyl 1680 p-hydroxyphenylmethyl 1681 p-nitrophenylmethyl 1682 p-aminophenylroethyl 1683 “4-(N,N- dimethylandno) phenylmethyl" 1684 benzyl 1685 l-pyrolylmethyl 1686 l-pyrazolylmethyl 1687 l-inu.dazolylmetbyl 1688 l-indolylmethyl 1689 l-triazolyln'ethyl 1690 l-tetrazolylmethyl 1691 2-pyridylmethyl 1692 3-pyridylmethyl 1693 4 -pyridylxoethyl 1694 cyclohexylmethyl 1695 2-naphthyljnethyl 1696 3-naphthyl®ethyl 1697 2-thiophenylmethyl 1698 4- (l-n\ethyl) piperidinyl-methyl 1699 "(3,4- methylenedioxyphenyl)Tnethyl 1700 2-thienylmethyl 1701 4-biphenylmethyl 1702 pyrimidinyln>ethyl 1703 2“benzothiazolylmethyl 1704 2-benzothiophenylxnethyl 1705 2-thiomethylethyl 1706 2-thiomethylmethyl 1707 2-methylpropyl 1708 2-irvethylbutyl 1709 3-methylbutyl 1710 cyclopropylmethyl 1711 cyclobutylmethyl 1712 cyclopentylmethyl 1713 p-hydroxyphenylmethyl 1714 p-nitrophenylmethyl 1715 p-amlnophenylroethyl 1716 "4-{K,N- dimethylamino) phenylmethyl' 1717 benzyl 1718 l-pyrolylmethyl 1719 l-pyrazolyljnethyl 1720 l-imldazolylmethyl LV 10096 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-pentyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-inethylbutyl 3-rnethylbutyl 3-roethylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 2-rnethylbutyl 2-methylbutyl 2-methylbutyl 2-methylbutyl 106

Table _4 1721 1-indolylmethyl 2-roethylbutyl 1722 l-triazolylmethyl 2-methylbutyl 1723 l-tetrazolylinethyl 2-methylbutyl 1724 2-pyridylmethyl 2-methylbutyl 1725 3-pyridylmethyl 2-methylbutyl 1726 4-pyridylmethyl 2-methylbutyl 1727 cyclohexylmethyl 2-methylbutyl 1728 2-naphthylmethyl 2-methylbutyl 1729 3-naphthylmethyl 2-inethylbutyl 1730 2-thiophenylmethyl 2-methylbutyl 1731 4-(1-methyl)piperidinyl-methyl 2-methylbutyl 1732 "(3,4- inethylenedioxyphenyl)methyl" 2-methylbutyl 1733 2-thienylmethyl 2-methylbutyl 1734 4-biphenylmethyl 2-methylbutyl 1735 pyrimidinyln\ethyl 2-methylbutyl 1736 2-benzothiazolylmethyl 2-methylbutyl 1737 2-benzothiophenylmethyl 2-methylbutyl 1738 2-thiomethylethyl 2-methylbutyl 1739 2-thiomethylmethyl 2-methylbutyl 1740 2-methylpropyl 2-methylbutyl 1741 2-methylbutyl 2-methylbutyl 1742 3-methylbutyl 2-methylbutyl 1743 cyclopropylmethyl 2-methylbutyl 1744 cyclobutylmethyl 2-methylbutyl 1745 cyclopentylmethyl 2-methylbutyl 1746 p-hydroxyphenylmethyl 2-methylbutyl 1747 p-nitrophenyljnethyl 2-methylbutyl 1748 p-aminophenylmethyl 2-methylbutyl 1749 "4-{N,N- dimethylami.no) phenylmethyl" 2-methylbutyl 1750 b«nzyl propargyl 1751 l-pyrolylmethyl propargyl 1752 l-pyrazolylmethyl propargyl 1753 l-imidazolylmethyl propargyl 1754 l-indolylmethyl propargyl 1755 l~triazolylmethyl propargyl 1756 l-tetrazolylmethyl propargyl 1757 2-pyridylmethyl propargyl 1758 3-pyridylmethyl propargyl 1759 4-pyridylmethyl propargyl 1760 cyclohexylmethyl propargyl 1761 2-naphthylmethyl propargyl 1762 3-naphthylmethy1 propargyl 1763 2-thiophenylmethyl propargyl 1764 4- (l-methyl)piperidinyl-methyl propargyl 1765 "(3,4- methy lenedloxyphenyl) methyl" propargyl 1766 2-thienylmethyl propargyl 1767 4-biphenylmethy1 propargyl 1768 pyrimidinylmethyl propargyl 1769 2-benzothiazolylmethyl propargyl 1770 2-benzothiophēnylmethyl propargyl 1771 2-thiomethylethyl propargyl 1772 2-thiomethylroethyl propatgyl 107LV 10096

Table 4 1773 2-methylpropyl proparyyl 1774 2-methylbutyl propargyl 1775 3-methylbutyl propargyl 1776 cyclopropylmethyl propargyl 1777 cyclobutylmethyl propargyl 1778 cyclopentylmethyl propargyl 1779 p-hydroxyphenylmethyl propargyl 1780 p-nitrophenylmethyl propargyl 1781 p-aminophenylmethyl propargyl 1782 "4-(N,N- dimethylamino) phenylmethyl" propargyl 1783 benzyl cyclobutyl 1784 l-pyrolylmethyl cyclobutyl 1785 l-pyrazolylmethyl cyclobutyl 1786 1-imidazoly lmethy1 cyclobutyl 1787 l-indolylroethyl cyclobutyl 1788 l-triazolylmethyl cyclobutyl 1789 l-tetrazolylmethyl cyclobutyl 1790 2-pyridylmethyl cyclobutyl 1791 3-pyridylroethyl cyclobutyl 1792 4-pyridylmethyl cyclobutyl 1793 cyclohexylmethyl cyclobutyl 1794 2-naphthylmethyI cyclobutyl 1795 3-naphthylmethyl cyclobutyl 1796 2-thiophenylmethyl cyclobutyl 1797 4- (l-methyl)piperidinyl-methyl cyclobutyl 1798 "(3,4* methylenedioxyphenyl)methyl" cyclobutyl 1799 2-thienylmethyl cyclobutyl 1800 4-biphenylmethyl cyclobutyl 1801 pyrimidinylmethyl cyclobutyl 1802 2-benzothiazolylmethyl cyclobutyl 1803 2-benzothiophenylmethyl cyclobutyl 1804 2-thiomethylethyl cyclobutyl 1805 2-thiomethylmethyl cyclobutyl 1806 2-methylpropyl cyclobutyl 1807 2-methylbutyl cyclobutyl 1808 3-methylbutyl cyclobutyl 1809 cyclopropylmethyl cyclobutyl 1810 cyclobutylmethyl cyclobutyl 1811 cyclopentylmethyl cyclobutyl 1812 p-hydroxyphenylmethyl cyclobutyl 1813 p-nitrophenylmethyl cyclobutyl 1814 p-aminophenylmethyl cyclobutyl 1815 "4-(N,N- dimethylamino) phenylmethyl" cyclobutyl 1816 benzyl cyclobutylmethyl 1817 l-pyrolylmethyl cyclobutylmethyl 1818 l-pyrazolylmethyl cyclobutylmethyl 1819 1-imidazolylmethyl cyclobutylmethyl 1820 l-indolylmethyl cyclobutylmethyl 1821 l-triazolylmethyl cyclobutylmethyl 1822 l-tetrazolylmethyl cyclobutylmethyl 1823 2-pyridylmethyl cyclobutylmethyl 1824 3-pyridylmethyl cyclobutylmethyl 1825 4-pyridylmethyl cyclobutylmethyl 108

Table 4 1826 cyclohexylmethyl cyclobutylmethyl 1827 2-naphthylmethyl cyclobutylmethyl 1828 3-naphthylmethyl cyclobutylmethyl 1829 2-thiophenylmethyl cyclobutylmethyl 1830 4-(l-methyl)piperidinyl- methyl cyc1obutylmethyl 1831 "(3,4- methylenedioxyphenyl) methyl" cyc1obutylmethy1 1832 2-thienylmethyl cyclobutylaethyl 1833 4-biphenylmethyl cyclobutylmethyl 1634 pyrimidinylmethyl cyclobutyl«ethyl 1835 2-benzothiazolylmethyl cyclobutylmethyl 1836 2-benzothiophenylmethyl cyclobutylmethyl 1837 2-thiomethylethyl cyclobutylmethyl 1838 2-thiomethylmethyl cyclobutylmethyl 1839 2-methylpropyl cyclobutylmethyl 1840 2-methylbutyl cyclobutyljnethyl 1841 3-methylbutyl cyclobutylffiethyl 1842 cyclopropylmethyl cyclobutylmethyl 1843 cyclobutylmethyl cyclobutylmethyl 1844 cyclopentylmethyl cyclobutylmethyl 1845 p-hydroxyphenylmethyl cyclobutylmethyl 1846 p-nitrophenylmethyl cyclobutylmethyl 1847 p-aminophenylmethyl cyclobutylmethyl 1848 "4-<N,N- dimethylamino)phenylmethyl" cyclobutylmethyl 1849 benzyl cyclopentyl 1850 l-pyrolylmethyl cyclopentyl 1851 l-pyrazolyljnethyl cyclopentyl 1852 1-imidazο1y lmethy1 cyclopentyl 1853 l-indolylmethyl cyclopentyl 1854 l-triazolylmethyl cyclopentyl 1855 l-tetrazolylmethyl cyclopentyl 1856 2-pyridylmethyl cyclopentyl 1857 3-pyridylmethyl cyclopentyl 1858 4-pyridylmethyl cyclopentyl 1859 cyclohexylmethyl cyclopentyl 1860 2-naphthylroethyl cyclopentyl 1861 3-naphthylmethyl cyclopentyl 1862 2-thiophenylmethyl cyclopentyl 1863 4- (l-methyl)piperidinyl-methyl cyclopentyl 1864 •(3,4- methylenedioxyphenyl)inethyl" cyclopentyl 1865 2-thienylmethyl cyclopentyl 1866 4-biphenylmethyl cyclopentyl 1867 py r imid i nylme t hy1 cyclopentyl 1868 2-benzothiazolylmethyl cyclopentyl 1869 2-benzothiophenylmethyl cyclopentyl 1870 2-thiomethylethyl cyclopentyl 1871 2-thiomethylmethyl cyclopentyl 1872 2-methylpropyl cyclopentyl 1873 2-methylbutyl cyclopentyl 1874 3-methylbutyl cyclopentyl 1875 cyclopropylmethyl cyclopentyl 1876 cyclobutylmethyl cyclopentyl 1877 cyclopentylmethyl cyclopentyl 109

109 Tabl£.JL 1878 p-hydroxyphenylmethyl 1879 p-nitrophenylmethyl 1880 p-aminophenylmethyl 1881 "4-{N,N- dimethylamino)phenylmethyl" 1882 benzyl 1883 1-pyrolylmethyl 1884 l-pyrazolylmethyl 1885 l-imidazolyljnethyl 1886 l-indolylinethyl 1887 l-triazolylmethyl 1888 l-tetrazolylmethyl 1889 2-pyridylmethyl 1890 3-pyridylmethyl 1891 4-pyridylmethyl 1892 cyclohexylmethyl 1893 2-naphthylmethyl 1894 3-naphthylmethyl 1895 2-thiophenylmethyl 1896 4-(l-methyl)piperidinyl-methyl 1897 "(3,4- methylenedioxyphenyl)wethyl' 1898 2-thienylmethyl 1899 4-biphenylmethyl 1900 pyrimidinylmethyl 1901 2-benzothiazolylmethyl 1902 2-benzothiophenylmethyl 1903 2-thiomethylethyl 1904 2-thiomethylmethyl 1905 2-methylpropyl 1906 2-methylbutyl 1907 3-methylbutyl 1908 cyclopropylmethyl 1909 cyclobutylmethyl 1910 cycloperitylmethyl 1911 p-hydroxyphenylmethyl 1912 p-nitrophenylmethyl 1913 p-arainophenylmethyl 1914 "4-(N,N- dimethylamino)phenylmethyl" 1915 benzyl 1916 l-pyrolylnvethyl 1917 l-pyrazolylmethyl 1918 l-inddazolylmethyl 1919 1-indolylmethy1 1920 l-triazolylroethyl 1921 l-tetrazolylmethyl 1922 2-pyridylmethyl 1923 3-pyridylmethyl 1924 4-pyridylmethyl 1925 cyclohexylmethyl 1926 2-naphthylmethyl 1927 3-naphthylmethyl 1928 2-thiophenylmethyl 1929 4-(l-methyl)piperidinyl- methyl LV 10096 cyclopentyl cyclopentyl cyclopentyl cyclopentyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylioethyl cyclopentylmethyl cyclopentylmethyl cyclopentylroethyl cyclopentyl»ethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylroethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyc1opentylmethy1 cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylffiethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl cyclopentyl®ethyl cyclopentylmethyl cyclopentylmethyl cyclopentylmethyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl 110

Table 4 1930 "(3,4- methylenedioxypKenyl) methyl· l-hexyl 1931 2-thienylmethyl l-hexyl 1932 4 -b iphe ny lme t hy 1 l-hexyl 1933 pyrimidinylmethyl l-hexyl 1934 2-ben2othiazolylmethyl l-hexyl 1935 2-benzothiophenylmethyl l-hexyl 1936 2-thiomethylethyl l-hexyl 1937 2-thiomethylmethyl l-hexyl 1938 2-methylpropyl l-hexyl 1939 2-methylbutyl l-hexyl 1940 3-methylbutyl l-hexyl 1941 cyclopropylmethyl l-hexyl 1942 cyclobutylmethyl l-hexyl 1943 cyclopentylmethyl l-hexyl 1944 p-hydroxyphenylmethyl l-hexyl 1945 p-nit rophenylmethyl l-hexyl 1946 p-aminophenylmethyl l-hexyl 1947 "4-(N,N- dimethylamino) phenylmethyl" l-hexyl 1948 benzyl 4-methylpentyl 1949 l-pyrolylmethyl 4-methylpentyl 1950 l-pyrazolylmethyl 4-methylpentyl 1951 l-imidazolylmethyl 4-methylpentyl 1952 l-indolylmethyl 4-methylpentyl 1953 l-triazolylmethyl 4-methylpentyl 1954 l-tetrazolylmethyl 4-methylpenty1 1955 2-pyridylmethyl 4-methylpentyl 1956 3-pyridylmethyl 4-methylpentyl 1957 4-pyridylmethyl 4-methylpentyl 1958 cyclohexylmethyl 4-methylpentyl 1959 2-naphthylmethyl 4-methylpentyl 1960 3-naphthylmethyl 4-methylpentyl 1961 2-thiophenylmethyl 4-methylpentyl 1962 4-{l-methyl)piperidinyl- methyl 4-methylpentyl 1963 "(3,4- methylenedioxyphenyl) methyl" 4-methylpentyl 1964 2-thienylmethyl 4-methylpentyl 1965 4-biphenylroethy1 4-methylpentyl 1966 pyrimidinylmethyl 4-methylpentyl 1967 2-benzothia zolylmethyl 4-methylpentyl 1968 2-benzothiophenylmethyl 4-methylpentyl 1969 2-thiomethylethyl 4-methylpentyl 1970 2-thiomethylmethyl 4-methylpentyl 1971 2-methylpropyl 4-methylpentyl 1972 2-methylbutyl 4-methylpentyl 1973 3-methylbutyl 4-methylpentyl 1974 cyclopropylmethyl 4-methylpentyl 1975 cyclobutylmethyl 4-methylpentyl 1976 cyclopentylmethyl 4-methylpentyl 1977 p-hydroxyphenylmethyl 4-methylpentyl 1978 p-n it r ophenylme thyl 4-methylpentyl 1979 p-aminophenylmethyl 4-methylpentyl 1980 "4-(K,N- dimethylami.no) phenylmethyl" 4-methylpentyl 1981 benzyl 3-methylpentyl 111 LV 10096 labie.. 4. 1962 l-pyrolylmethyl 3-methylpentyl 1983 l-pyrazolylmethyl' 3-methylpentyl 1984 l-imidazolylJti€thyl 3-methylpentyl 1985 l-indolylmethyl 3-methylpentyl 1986 l-triazolylmethyl 3-methylpentyl 1987 l-tetrazolylmethyl 3-methylpentyl 1988 2-pyridylmethyl 3-methylpentyl 1989 3-pyridylmethyl 3-methylpentyl 1990 4-pyridylmethyl 3-methylpentyl 1991 cyclohexybnethyl 3-methylpentyl 1992 2 -naphthylinethyl 3-methylpentyl 1993 3-naphthylroethyl 3-methylpentyl 1994 2-thiophenylmethyl 3-methylpentyl 1995 4- (l-methyl)piperidinyl-methyl 3-methylpentyl 1996 "(3,4- methylenedioxyphenyl) roethyl" 3 -me t hylpentyl 1997 2-thienylmethyl 3-methylpentyl 1998 4-biphenylmethyl 3-methylpentyl 1999 pyrimidinylmethyl 3-methylpentyl 2000 2-benzothiazolylmethyl 3-methylpentyl 2001 2-benzothiophenylmethyl 3-methylpentyl 2002 2-thiomethylethyl 3-methylpentyl 2003 2-thiomethylmethyl 3-methylpentyl 2004 2-methylpropyl 3-methylpentyl 2005 2-methylbutyl 3-methylpentyl 2006 3-methylbutyl 3-methylpentyl 2007 cyclopropylmethyl 3-methylpentyl 2008 cyclobutylir>ethyl 3-methylpentyl 2009 cyclopentylmethyl 3-methylpentyl 2010 p-hydroxyphenylmethyl 3-methylpentyl 2011 p-nitrophenylmethyl 3-methylpentyl 2012 p-aminophenylmethyl 3-methylpentyl 2013 "4- (N,N- dimethylami.no) phenylmethyl" 3-methylpentyl 2014 benzyl isopropyl 2015 1-pyrolylmethyl isopropyl 2016 l-pyrazolylmethyl isopropyl 2017 l-imidazolylmethyl isopropyl 2018 l-indolylmethyl isopropyl 2019 l-triazolylmethyl isopropyl 2020 l-tetrazolylmethyl isopropyl 2021 2-pyridylmethyl iaopropyl 2022 3-pyridylmethyl isopropyl 2023 4-pyridylmethyl isopropyl 2024 cyclohexylroethyl isopropyl 2025 2-naphthylmethyl isopropyl 2026 3-naphthylmethyl isopropyl 2027 2-thiophenylmethyl isopropyl 2028 4 - (1-methy 1) pipe r idiny 1-methyl isopropyl 2029 "(3,4- methylenedioxyphenyl) methyl" isopropyl 2030 2-thienylmethyl isopropyl 2031 4-biphenylmethyl isopropyl 2032 pyrimidinylmethyl isopropyl 2033 2-benzothiazolylmethyl isopropyl 112

Iable-4 2034 2-benzothiophenylmethyl isopropyl 2035 2-thiomethylethyl iaopropyl 2036 2-thiomethylmethyl isopropyl 2037 2-rnethylpropyl iaopropyl 2038 2-methylbutyl iaopropyl 2039 3-methylbutyl isopropyl 2040 cyclopropylroethyl isopropyl 2041 cyclobutylmethyl iaopropyl 2042 cyclopentylmethyl iaopropyl 2043 p-hydroxyphenylmethyl iaopropyl 2044 p-nit rophenylmethyl iaopropyl 2045 p-aminophenyļmethyl iaopropyl 2046 "4-(N,N- dimethylamino) phenylmethyl" iaopropyl 2047 benzyl 3-methylbutyl 2048 l-pyrolylraethyl 3-methylbutyl 2049 l-pyrazolylroethyl 3-methylbutyl 2050 l-imidazolylmethyl 3-methylbutyl 2051 l-indolylmethyl 3-methylbutyl 2052 l-triazolylmethyl 3-methylbutyl 2053 l-tetrazolylmethyl 3-methylbutyl 2054 2-pyridylmethyl 3-methylbutyl 2055 3-pyridylmethyl 3-methylbutyl 2056 4-pyridylmethyl 3-methylbutyl 2057 cyclohexylmethyl 3-methylbutyl 2058 2-naphthylmethyl 3-jnethylbutyl 2059 3-naphthylmethyl 3-methylbutyl 2060 2-thiophenylmethyl 3-methylbutyl 2061 4 - (l-methyl)piperidinyl-Jtvethyl 3-methylbutyl 2062 "(3,4- methylenedioxyphenyl) methyl" 3-methylbutyl 2063 2-thienylmethyl 3-methylbutyl 2064 4-biphenylmethyl 3-methylbutyl 2065 pyrlmidinylmethyl 3-methylbutyl 2066 2-benzothiazolylmethyl 3-methylbutyl 2067 2-benzothiophenylmethyl 3-methylbutyl 2068 2-thiomethylethyl . 3-methylbutyl 2069 2-thiomethylmethyl 3-methylbutyl 2070 2-methylpropyl 3-methylbutyl 2071 2-methylbutyl 3-methylbutyl 2072 3-methylbutyl 3-methylbutyl 2073 cyclopropylroethyl 3-methylbutyl 2074 cyclobutylroethyl 3-methylbutyl 2075 cyclopentylmethyl 3-methylbutyl 2076 p-hydroxyphenylmethyl 3-methylbutyl 2077 p-nit rophenylmethyl 3-jnethylbutyl 2078 p-aminophenylmethyl 3-methylbutyl 2079 "4-{N,N- dimethylamino) phenylmethyl" 3-wethylbutyl 2080 benzyl 2-phenylethyl 2081 1-pyrolylmethyl 2-phenylethyl 2082 1-pyrazolylmethy1 2-phenylethyl 2083 l-imidazolylmethyl 2-phenylethyl 2084 l-indolylmethyl 2-phenylethyl 2085 l-triazolylmethyl 2-phenylethyl 2086 1-tet ra zolylnve thy 1 2-phenylethyl 113labie 4 LV 10096 2087 2-pyridylmethyl 2-phenylethyl 2088 3-pyridylmethyl' 2-phenylethyl 2089 4-pyridyljnethyl 2-phenylethyl 2090 cyclohexylmethyl 2-phenylethyl 2091 2-naphthylmethyl 2-phenylethyl 2092 3-naphthylmethyl 2-phenylethyl 2093 2-thiophenylroethyl 2-phenylethyl 2094 4- (l-methyl)piperidinyl-roethyl 2-phenylethyl 2095 "(3,4- methylenedioxyphenyl) methyl" 2-phenylethyl 2096 2-thienylmethyl 2-phenylethyl 2097 4-biphenylmethyl 2-phenylethyl 2098 pyrimidinylmethyl 2-phenylethyl 2099 2-benzothiazolylmethyl 2-phenylethyl 2100 2-benzothiophenylmethyl 2-phenylethyl 2101 2-thiomethylethyl 2-phenylethyl 2102 2-thiomethylmethyl 2-phenylethyl 2103 2-methylpropyl 2-phenylethyl 2104 2-methylbutyl 2-phenylethyl 2105 3-methylbutyl 2-phenylethyl 2106 cyclopropylmethyl 2-phenylethyl 2107 cyclobutylmethyl 2-phenylethyl 2108 cyclopentylmethyl 2-phenylethyl 2109 p-hydroxyphenylmethyl 2-phenylethyl 2110 p-nitrophenylmethyl 2-phenylethyl 2111 p-aminophenylmethyl 2-phenylethyl 2112 "4-<N,N- dijnethylami.no) phenylmethyl" 2-phenylethyl 2113 benzyl 3-phenylpropyl 2114 l-pyrolylmethyl 3-phenylpropyl 2115 l-pyrazolylmethyl 3-phenylpropyl 2116 l-imidazolylmethyl 3-phenylpropyl 2117 l-indolylmethyl 3-phenylpropyl 2118 l-triazolylmethyl 3-phenylpropyl 2119 l-tetrazolylmethyl 3-phenylpropyl 2120 2-pyridylroethyl 3-phenylpropyl 2121 3-pyridylmethyl 3-phenylpropyl 2122 4-pyridylroethyl 3-phenylpropyl 2123 čyclohexylmethyl 3-phenylpropyl 2124 2-naphthylmethyl 3-phenylpropyl 2125 3-naphthylmethyl 3-phenylpropyl 2126 2-thiophenylmethyl 3-phenylpropyl 2127 4-(l-methyl)piperidinyl-methyl 3-phenylpropyl 2128 "(3,4- methylenedloxyphenyl)methyl" 3-phenylpropyl 2129 2-thienylroethyl 3-phenylpropyl 2130 4-biphenylmethyl 3-phenylpropyl 2131 pyrimidinylmethyl 3-phenylpropyl 2132 2-benzothiazolyljnethyl 3-phenylpropyl 2133 2-benzothiophenylmethyl 3-phenylpropyl 2134 2-thiomethylethyl 3-phenylpropyl 2135 2-thiomethylmethyl 3-phenylpropyl 2136 2-roethylpropyl 3-phenylpropyl 2137 2-methylbutyl 3-phenylpropyl 2138 3-methylbuty1 3-phenylpropyl 114

Table 4 2139 cyclopropylmethyl 3-phenylpropyl 2140 cyclobutylmethyl 3-phenylpropyl 2141 cyclopentylmethyl 3-phenylpropyl 2142 p-hydroxyphenylmethyl 3-phenylpropyl 2143 p-nitrophenylmethyl 3-phenylpropyl 2144 p-aminophenylmethyl 3-phenylpropyl .2145 "4-(N,N- dimethylamino) phenylmethyl" 3-phenylpropyl 2146 benzyl "2- (N, N-dimethylamino) ethyl 2147 l-pyrolylmethyl "2- (N, N-dimethylami.no) ethyl 2148 l-pyrazolylmethyl "2- (N,N-dimethylamino)ethyl 2149 l-imidazolylmethyl "2- (N, N-dimethylamino) ethyl 2150 l-indolylmethyl "2-(N,N-dimethylamino)ethyl 2151 l-triazolylmethyl "2- (N, N-dimethylamino) ethyl 2152 l-tetrazolylmethyl "2-(N,N-dimethylaraino)ethyl 2153 2-pyridylmethy1 "2- (N, N-dimethylamino) ethyl 2154 3-pyridylmethyl "2- (N, N-dimethylamino) ethyl 2155 4-pyridylmethyl "2-(N,N-dimethylamino)ethyl 2156 cyclohexylmethyl "2-(N,N-dimethylamino)ethyl' 2157 2-naphthylmethyl "2-(N,N-dimethylamino)ethyl' 2158 3-naphthylmethyl "2- (N, N-dimethylaid.no) ethyl’ 2159 2-thiophenylmethyl "2-(N,H-dimethylamino)ethyl’ 2160 4- (l-methyl)piperidinyl-methyl "2- (N, N-dimethylamino) ethyl' 2161 "(3,4- methylenedioxyphenyl)methyl* "2-(N,N-dimethylamino)ethyl’ 2162 2-thienylmethyl "2-(N,N-dimethylamino)ethyl' 2163 4-biphenylmethyl "2-(N,N-diroethylamino)ethyl' 2164 pyrimidinylmethyl "2-(N,N-dimethylamino)ethyl' 2165 2-benzothiazolylmethyl "2-(N,N-dimethylamino)ethyl' 2166 2-benzothiophenylmethyl "2-(N,N-dimethylamino)ethyl' 2167 2-thionvethylethyl "2-(N,N-dimethylamino)ethyl' 2168 2-thiomethylmethyl "2-(N,N-dimethylamino)ethyl' 2169 2-methylpropyl "2-(N,N-dimethylamino)ethyl' 2170 2-methylbutyl "2-(N,N-dimethylamino)ethyl' 2171 3-inethylbutyl "2-(N,N-diroethylamino)ethyl' 2172 cyclopropylmethyl "2-(N,N-dimethylamino)ethyl' 2173 cyclobutylmethyl "2-(N,N-dimethylamino)ethyl' 2174 cyclopentylmethyl "2-(N,N-dimethylamino)ethyl' 2175 p-hydroxyphenylmethyl "2-(N,N-dimethylamino)ethyl' 2176 p-nitrophenylmethyl "2-(N,N-dimethylamino)ethyl' 2177 p-aminophenylmethyl "2-(N,N-dimethylamino)ethyl' 2178 "4-(N,N- dimethylamino)phenylmethyl" "2- (N, N-dimethylanu.no) ethyl' 2179 benzyl 3-oxetanylmethyl 2180 l-pyrolylmethyl 3-oxetanylmethyl 2181 l-pyrazolylmethyl 3-oxetanylmethyl 2182 l-imidazolylmethyl 3-oxetanylmethyl 2183 l-indolylmethyl 3-oxetanylmethyl 2184 l-triazolylmethyl 3-oxetanylmethyl 2185 l-tetrazolylmethyl 3-oxetanylmethyl 2186 2-pyridylmethyl 3-oxetanylmethyl 2187 3-pyridylmethyl 3-oxetanylmethyl 2188 4-pyridylmethyl 3-oxetanylmethyl 2189 cyclohexylmethyl 3-oxetanylmethyl 2190 2-naphthy lme thy1 3-oxetanylmethyl 2191 3-naphthylmethyl 3-oxetanylmethyl 115 LV 10096 labie 4. 2192 2-thiophenylmethyl 3-oxetanylmethyl 2193 4- (l-methyl)piperidinyl-methyl 3-oxetanylroethyl 2194 *<3,4- nvethylenedioxyphenyl) methyl" 3-oxetanylmethyl 2195 2-thienylmethyl 3-oxetanylroethyl 2196 4-biphenylmethyl 3-oxetanylmethyl 2197 pyrimidinylmethyl 3-oxetanylmethyl 2198 2-benzothiazolylmethyl 3-oxetanylmethyl 2199 2-benzothiophenylmethyl 3-oxetanylmethyl 2200 2-thiomethylethyl 3-oxetanylmethyl 2201 2-thiomethylmethyl 3-oxetanylroethyl 2202 2-methylpropyl 3-oxetanylmethyl 2203 2-methylbutyl 3-oxetanylmethyl 2204 3-methylbutyl 3-oxetanylmethyl 2205 cyclopropylmethyl 3-oxetanylmethyl 2206 cyclobutylmethyl 3-oxetanylmethyl 2207 cyclopentylmethyl 3-oxetanylmethyl 2208 p-hydroxyphenylmethyl 3-oxetanylmethyl 2209 p-nitrophenylmethyl 3-oxetanylmethyl 2210 p-ami.nophenylmet.hyl 3-oxetanylroethyl 2211 "4- (N,lidiniet hylairu.no) phenylmethyl" 3-oxetanylmethyl 2212 benzyl 2-tetrahydrofuranyl 2213 l-pyrolylmethyl 2-tetrahydrofuranyl 2214 l-pyrazolylmethyl 2-tetrahydrofuranyl 2215 l-imidazolylmethyl 2-tetrahydrofuranyl 2216 l-indolylmethyl 2-tetrahydrofuranyl 2217 l-triazolylmethyl 2-tetrahydrofuranyl 2218 l-tetrazolylmethyl 2-tetrahydrofuranyl 2219 2-pyridylmethyl 2-tetrahydxofuranyl 2220 3-pyridylmethyl 2-tetrahydrofuranyl 2221 4-pyridylmethyl 2-tetrahydrofuranyl 2222 cyclohexylmethyl 2-tetrahydrofuranyl 2223 2-naphthylmethyl 2-tetrahydrofuranyl 2224 3-naphthylmethyl 2-tetrahydrofuranyl 2225 2-thiophenylmethyl 2-tetrahydrofuranyl 2226 4-<l-methyl)piperidinyl- methyl 2-tetrahydrofuranyl 2227 "(3,4- methylenedioxyphenyl)methyl" 2-tetrahydrofuranyl 2228 2-thienylmethyl 2-tetrahydrofuranyl 2229 4-biphenylmethyl 2-tetrahydrofuranyl 2230 pyrimidinylmethyl 2-tetrahydrofuranyl 2231 2-benzothiazolylmethyl 2-tetrahydrofuranyl 2232 2-benzothiophenylmethyl 2-tetrahydrofuranyl 2233 2-thiomethylethyl 2-tetrahydrofuranyl 2234 2-thiomethylmethyl 2-tetrahydrofuranyl 2235 2-methylpropyl 2-tetrahydrofuranyl 2236 2-methylbutyl 2-tet rahydrofuranyl 2237 3-methylbutyl 2-tetrahydrofuranyl 2238 cyclopropylmethyl 2-tetrahydrofuranyl 2239 cyclobutylmethyl 2-tetrahydrofuranyl 2240 cyclopentylmethyl 2-tetrahydrofuranyl 2241 p-hydroxyphenylmethyl 2-tetrahydrofuranyl 2242 p-nitrophenylroethyl 2-tetrahydrofuranyl 2243 p-aminophenylmethyl 2-tetrahydrofuranyl 116

Table 4 2244 "4-(N,N- dimethylamino) pheriylmethyl" 2-tetrahydrofuranyl 2245 benzyl 2-methoxypropyl 2246 l-pyrolylmethyl 2-methoxypropy1 2247 l-pyrazolylmethyl 2-methoxypropy1 2248 l-imidazolylmethyl 2-methoxypropyl 2249 l-indolylmethyl 2-methoxypropyl 2250 l-triazolylmethyl 2-methoxypropyl 2251 l-tetrazolylmethyl 2-methoxypropyl 2252 2-pyridylmethyl 2-methoxypropyl 2253 3-pyridylmethyl 2-methoxypropyl 2254 4-pyridylmethyl 2-methoxypropyl 2255 cyclohexylmethyl 2-methoxypropyl 2256 2-naphthylmethyl 2-methoxypropyl 2257 3-naphthylmethyl 2-methoxypropyl 2258 2-thiophenylmethyl 2-me thoxypropyl 2259 4-(l-methyl)piperidinyl- methyl 2-methoxypropyl 2260 "(3,4- methylenedioxyphenyl) methyl" 2-methoxypropyl 2261 2-thienylmethyl 2-methoxypropyl 2262 4-biphenylmethyl 2-methoxypropyl 2263 pyrimidinylmethyl 2-methoxypropyl 2264 2-benzothiazolylmethyl 2-methoxypropyl 2265 2-benzothiophenylmethyl 2-methoxypropyl 2266 2-thiomethylethyl 2-methoxypropyl 2267 2-thiomethylmethyl 2-methoxypropyl 2268 2-methylpropyl 2-methoxypropyl 2269 2-methylbutyl 2-methoxypropyl 2270 3-methylbutyl. 2-methoxypropyl 2271 cyclopropylmethyl 2-methoxypropyl 2272 cyclobutylmethyl 2-methoxypropyl 2273 cyclopentylmethyl 2-methoxypropyl 2274 p-hydroxyphenylmethyl 2-methoxypropyl 2275 p-nitrophenylmethyl 2-methoxypropyl 2276 p-aminophenylmethyl 2-methoxypropyl 2277 "4-(N,N- dimethylami.no) phenylmethyl" 2-methoxypropyl 2278 benzyl 2-ethoxyethyl 2279 l-pyrolylmethyl 2-ethoxyethyl 2280 1-pyra zolylmethyl 2-ethoxyethyl 2281 l-imidazolylmethyl 2-ethoxyethyl 2282 l-indolylmethyl 2-ethoxyethyl 2283 l-triazolylmethyl 2-ethoxyethyl 2284 l-tetrazolylmethyl 2-ethoxyethyl 2285 2-pyridylmethyl 2-ethoxyethyl 2286 3-pyridylmethyl 2-ethoxyethyl 2287 4-pyridylmethyl 2-ethoxyethyl 2288 cyclohexylmethyl 2-ethoxyethyl 2289 2-naphthylmethyl 2-ethoxyethyl 2290 3-naphthylmethyl 2-ethoxyethyl 2291 2-thiophenylmethyl 2-ethoxyethyl 2292 4-(l-methyl)piperidinyl-methyl 2-ethoxyethyl 2293 "(3,4- methylenedioxyphenyl)methyl" 2-ethoxyethyl 2294 2-thienylmethyl 2-ethoxyethyl 117 LV 10096

Tablfi-i. 2295 4-biphenylmethyl 2-ethoxyethyl 2296 pyrimidinylmethyl 2-ethoxyethyl 2297 2-benzothiazolylm’ethyl 2-ethoxyethyl 2298 2-benzothiophenylmethy1 2-ethoxyethyl 2299 2-thiomethylethyl 2-ethoxyethyl 2300 2-thiomethylmethyl 2-ethoxyethyl 2301 2-methylpropyl 2-ethoxyethyl 2302 2-roethylbutyl 2-ethoxyethyl 2303 3-methylbutyl 2-ethoxyethyl 2304 cyclopropylmethyl 2-ethoxyethyl 2305 cyclobutylmethyl 2-ethoxyethyl 2306 cyclopentylmethyl 2-ethoxyethyl 2307 p-hydroxyphenylmethyl 2-ethoxyethyl 2308 p-nitrophenylmethyl 2-ethoxyethyl 2309 p-aminophenylmethyl 2-ethoxyethyl 2310 "4-{N,N- dimethylamino) phenylmethyl" 2-ethoxyethyl 2311 benzyl 2-(l-pyrolyl)ethyl 2312 1-pyrolylmethyl 2-(l-pyrolyl)ethyl 2313 l-pyrazolylmethyl 2-(l-pyrolyl)ethyl 2314 l-imidazoly]jnethyl 2-(l-pyrolyl)ethyl 2315 l-indolylraethyl 2-(l-pyrolyl)ethyl 2316 l-triazolylmethyl 2-(l-pyrolyl)ethyl 2317 l-tetrazolylmethyl 2-(l-pyrolyl)ethyl 2318 2-pyridylmethyl 2-(l-pyrolyl)ethyl 2319 3-pyridylmethyl 2-(l-pyrolyl)ethyl 2320 4-pyridylmethyl 2-(l-pyrolyl)ethyl 2321 cyclohexy]jnethyl 2-(l-pyrolyl)ethyl 2322 2-naphthyliivethyl 2-(l-pyrolyl)ethyl 2323 3-naphthyl»ethyl 2-(l-pyrolyl)ethyl 2324 2-thiophenylmethyl 2-(l-pyrolyl)ethyl 2325 4-(l-methyl)piperidinyl-methyl 2-(l-pyrolyl)ethyl 2326 "(3,4- methylenedioxyphenyl)methyl" 2-(l-pyrolyl)ethyl 2327 2-thienylΛethyl 2-(l-pyrolyl)ethyl 2328 4-biphen'ylmethyl 2-(l-pyrolyl)ethyl 2329 pyrimldinylmethyl 2-(l-pyrolyl)ethyl 2330 2-benzothiazolylmethyl 2-(l-pyrolyl)ethyl 2331 2-benzothiophenylmethyl 2-(l-pyrolyl)ethyl 2332 2-thiomethylethyl 2-(l-pyrolyl)ethyl 2333 2-thiomethylmethyl 2-(l-pyrolyl)ethyl 2334 2 -jne t hy lpr opyl 2-(l-pyrolyl)ethyl 2335 2-methylbutyl 2-{l-pyrolyl)ethyl 2336 3-methylbutyl 2-(l-pyrolyl)ethyl 2337 cyclopropylmethyl 2-{l-pyrolyl)ethyl 2338 cyclobutylniethyl 2-(l-pyrolyl)ethyl 2339 cyclopentylmethyl 2-(l-pyrolyl)ethyl 2340 p-hydroxyphenylmethyl 2-(l-pyrolyl)ethyl 2341 p-nitrophenylmethyl 2-(l-pyrolyl)ethyl 2342 p-aminophenylmethyl 2-(l-pyrolyl)ethyl 2343 "4-{N,N- diroethylami.no) phenylmethyl" 2-(l-pyrolyl)ethyl 2344 benzyl 2-(l-imidazolyl)ethyl 2345 1-pyrolylmethyl 2-(l-imidazolyl)ethyl 2346 l-pyrazolylmethyl 2-(l-imidazolyl)ethyl 2347 l-imidazolylmethyl 2-(l-imidazolyl)ethyl 118

Table 4 2348 l-indolylmethyl 2-(l-imidazolyl)ethyl 2349 l-triazolylmethyl 2- (l-imidazolyl)ethyl 2350 l-tetrazolylmethyl 2-(l-imidazolyl)ethyl 2351 2-pyridylmethyl 2-(l-imidazolyl)ethyl 2352 3-pyridylmethyl 2-(l-imidazolyl)ethyl 2353 4-pyridylmethyl 2-(l-imidazolyl)ethyl 2354 cyclohexylmethyl 2- (l-imidazolyl)ethyl 2355 2-naphthylmethyl 2-(l-imidazolyl)ethyl 2356 3-naphthylmethyl 2-(l-imidazolyl)ethyl 2357 2-thiophenylmethyl 2-(l-imidazolyl)ethyl 2358 4-(l-methyl) piperidinyl-methyl 2-(l-imidazolyl)ethyl 2359 "(3,4- methylenedioxyphenyl)methyl" 2-(l-imidazolyl)ethyl 2360 2-thienylmethyl 2-(l-imidazolyl)ethyl 2361 4-biphenylmethyl 2-(l-imidazolyl)ethyl 2362 pyrimidinylmethyl 2-(l-imidazolyl)ethyl 2363 2-benzothiazolylmethyl 2-(l-imidazolyl)ethyl 2364 2-benzothiophenylmethyl 2-(l-imidazolyl)ethyl 2365 2-thiomethylethyl 2- (l-imidazolyl)ethyl 2366 2-thiomethylmethyl 2-(l-imidazolyl)ethyl 2367 2-methylpropyl 2-(l-imidazolyl)ethyl 2368 2-methylbutyl 2-(l-imidazolyl)ethyl 2369 3-methylbutyl 2-(l-imidazolyl)ethyl 2370 cyclopropylmethyl 2-(l-imidazolyl)ethyl 2371 cyclobutylmethyl 2-(l-imidazolyl)ethyl 2372 cyclopentylmethyl 2-(l-imidazolyl) ethyl 2373 p-hydroxyphenylmethyl 2-(l-imidazolyl)ethyl 2374 p-nitrophenylmethyl 2-(l-imidazolyl)ethyl 2375 p-aminophenylmethyl 2-{l-imidazolyl)ethyl 2376 "4-{N,liti imethylamino) phenylmethyl" 2-(l-imidazolyl)ethyl 2377 benzyl 2-pyridylmethyl 2378 l-pyrolylmethyl 2-pyridylmethyl 2379 l-pyrazolylmethyl 2-pyridylmethyl 2380 l-imidazolylmethyl 2-pyridylmethyl 2381 l-indolylmethyl 2-pyridylmethyl 2382 l-triazolylmethyl 2-pyridylroethyl 2383 l-tetrazolylmethyl 2-pyridylmethy1 2384 2-pyridylmethyl 2-pyridylmethyl 2385 3-pyridylmethyl 2-pyridylmethyl 2386 4-pyridylmethyl 2-pyridylmethyl 2387 cyclohexylmethyl 2-pyridylmethyl 2388 2-naphthylmethyl 2-pyridylmethyl 2389 3-naphthylmethyl 2-pyridylmethyl 2390 2-thiophenylmethyl 2-pyridylmethyl 2391 4- (l-methyl) piperidinyl-methyl 2-pyridylmethyl 2392 "(3,4- methylenedioxyphenyl) methyl" 2-pyridylmethyl 2393 2-thienylmethyl 2-pyridylmethyl 2394 4-biphenylmethyl 2-pyridylmethyl 2395 pyrimidinylmethyl 2-pyrldylmethyl 2396 2-benzothiazolylmethyl 2-pyridylmethyl 2397 2-benzothiophenylmethyl 2-pyridylmethyl 2398 2-thiomethylethyl 2-pyridylmethyl 2399 2-thiomethylmethyl 2-pyridylmethyl 119 LV 10096 labie,.i 2400 2-methylpropyl 2-pyridylmethyl 2401 2-methylbutyl 2-pyridyLmethyl 2402 3-methylbutyl 2-pyridylmethyl 2403 cyclopropylmethyl 2-pyridylmethyl 2404 cyclobutylmethyl 2-pyridylmethy1 2405 cyclopentylmethyl 2-pyridylmethyl 2406 p-hydroxyphenylmethyl 2-pyridylmethy1 2407 p-nitrophenylmethyl 2-pyridylmethyl 2408 p-aminophenylmethyl 2-pyridylinethyl 2409 "4-(N,N- dimethylamino) phenylmethyl" 2-pyridylmethyl 2410 benzyl 2-thiomethylethyl 2411 l-pyrolylinethyl 2-thiomethylethyl 2412 l-pyrazolylroethyl 2-thiomethylethyl 2413 l-imidazolylJnethyl 2-thiomethylethyl 2414 l-indolylmethyl 2-thiomethylethyl 2415 l-triazolylJaethyl 2-thiomethylethyl 2416 l-tetrazolylmethyl 2-thiomethylethyl 2417 2-pyridylmethyl 2-thiomethylethyl 2418 3-pyridylmethyl 2-thiomethylethyl 2419 4-pyridylmethyl 2-thiomethylethyl 2420 cyclohexy]jnethyl 2-thiomethylethyl 2421 2-naphthylmethyl 2-thiomethylethyl 2422 3-naphthylmethyl 2-thiomethylethyl 2423 2-thiophenyln»ethyl 2-thiomethylethyl 2424 4- (l-methyl)piperidinyl-methyl 2-thioroethylethyl 2425 "(3,4- methylenedioxyphenyl)methyl" 2-thiomethylethyl 2426 2-thienylmethyl 2-thiomethylethyl 2427 4-biphenylmethyl 2-thiomethylethyl 2428 pyriīnidinylinethyl 2-thiomethylethyl 2429 2-benzothiazolylmethyl 2-thiomethylethyl 2430 2-benzothiophenylmethyl 2-thiomethylethyl 2431 2-thiomethylethyl 2-thiomethylethyl 2432 2-thiomethylmethyl 2-thiomethylethyl 2433 2-methylpropyl 2-thiomethylethyl 2434 2-methylbutyl 2-thiomethylethyl 2435 3-methylbutyl 2-thiomethylethyl 2436 cyclopropylmethyl 2-thiomethylethyl 2437 cyclobutylmethyl 2-thiomethylethyl 2438 cyclopentylmethyl 2-thiomethylethyl 2439 p-hydroxyphenylmethyl 2-thiomethylethyl 2440 p-nitrophenylmethyl 2-thiomethylethyl 2441 p-aminophenylmethyl 2-thiomethylethyl 2442 "4-(N,N- dimethylamino) phenylmethyl" 2-thiomethylethyl 120 Iablg-ϋ TABLE 5 Ο

R= Λ /«“ hT

Exampl.fi Number Rl R2 2443 benzyl "4-(N,N- dimethylamino)phenyl-methyl" 2444 l-pyrolylmethyl benzyl 2445 l-pyrazolybnethyl 1-pyrolylmethyl 2446 l-imidazolylmethyl l-pyrazolylioethyl 2447 l-indolylroethyl l-imidazolylmethyl 2448 l-triazolylmethyl 1-indolylmethyl 2449 l-tetrazolylmethyl l-triazolylmethyl 2450 2-pyridylmethyl l-tetrazolylmethyl 2451 3-pyridybn«thyl 2-pyridylmethyl 2452 4-pyridylmethyl 3-pyridylmethyl 2453 cyclohexyl»ethyl 4-pyridylmethy1 2454 2-naphthylmethyl cyclohexylroethyl 2455 3-naphthylmethyl 2-naphthylmethyl 2456 2-thiophenylmethyl 3-naphthylmethyl 2457 4-(l-methyl)piper-idinylmethyl 2-thiophenyljnethyl 2458 "(3,4-methylenedioxy- 4-{l-methyl)piperi- phenyl)methyl* dinyl-methyl 2459 2-thienylmethyl " (3,4-»ethylenedioxy·· phenyl)methyl" 2460 4-biphenylmethyl 2-thienylmethyl 2461 pyrimidinylmethyl 4-biphenylmethyl 2462 2-benzothiazolyl- methyl pyrimidinylmethyl 2463 2-benzothiophenyl- 2-benzothiazolyl- methyl methyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl allyl 2464 121 Table 5 2-thiomethylethyl 2-b€nzothiophenyl- LV 10096 allyl 2465 2-thiomethylmethyl methyl 2-thiomethylethyl allyl 2466 2-oethylpropyl 2-thiomethylmethyl allyl 2467 2-methylbutyl 2-methylpropyl allyl 2468 3-methylbutyl 2-methylbutyl allyl 2469 cyclopropylmethyl 3-methylbutyl allyl 2470 cyclobutylmethyl cyclopropylmethyl allyl 2471 cyclopentylmethyl cyclobutylmethyl allyl 2472 p-hydroxyphenyl-methyl cyclopentylroethyl allyl 2473 p-nitrophenylmethyl p-hydroxyphenyl-methyl allyl 2474 p-aminophenyl-methyl p-nit rophenylmethyl allyl 2475 "4-(N,N-dimethylam- p-aminophenyl-methyl allyl 2476 ino)phenylmethyl" benzyl "4-{N,N-dimethyl- propyl 2477 l-pyrolylmethyl amino)-phenyl-methyl" benzyl propyl 2478 l-pyrazolylmethyl l-pyrolylmethyl propyl 2479 l-imidazolylmethyl l-pyrazolylmethyl propyl 2480 l-indolylmethyl l-imidazolylmethyl propyl 2481 l-triazolylmethyl l-indolylmethyl propyl 2482 l-tetrazolylmethyl l-triazolylmethyl propyl 2483 2-pyridylmethyl l-tetrazolylmethyl propyl 2484 3-pyridylmethyl 2-pyridylmethyl propyl 2485 4-pyridylmethyl 3-pyridylmethyl propyl 2486 cyclohexylmethyl 4-pyridylmethyl propyl 2487 2-naphthylmethyl cyclohexylmethyl propyl 2488 3-naphthylmethyl 2-naphthylmethyl propyl 2489 2-thiophenylmethyl 3-naphthylmethyl propyl 2490 4-(l-methyl)- 2-thiophenylmethyl propyl 2491 pip«ridinyl-methyl (3# 4-methylene- 4-(l-methyl)- propyl 2492 dioxyphenyl)methyl· 2-thienylmethyl piperidinyl-methyl " (3,4-methylene- propyl 2493 4-biphenylmethyl dioxyphenyl)methyle 2-thienylmethyl propyl 2494 pyrimidinylmethyl 4-biphenylmethy1 propyl 2495 2-benzothiazolylmethyl pyrimidinylmethyl propyl 2496 2- 2-benzothiazolylmethyl pr°pyi 2497 benzothiophenylmethyl 2-thiomethylethyl 2- propyl 2498 2-thiomethylmethyl benzothiophenylmethyl 2-thiomethylethyl propyl 2499 2-methylpropyl 2-thiomethylmethxJ propyl 2500 2-methylbutyl 2-methylpropyl propyl 2501 3-methylbutyl 2-methylbutyl propyl 2502 cyclopropylmethyl 3-methylbutyl propyl 2503 cyclobutylmethyl cyclopropylmethyl propyl 2504 cyclopentylmethyl cyclobutylmethyl propyl 2505 p-hydroxyphenyl-methvl cyclopentylmethyl propyl 2506 p-nitrophenylmethyl p-hydroxyphenyl-methyl propyl 2507 p-aminophenyl-methyl p-nit rophenylmethyl propyl 2508 "4-(N,N-dimethyl- p-aminophenyl-methyl propyl 2509 amino) phenylmethyl" benzyl " 4 - (N,N-dimethyl- n-butyl 2510 l-pyrolylmethyl amino)phenylmethyl" benzyl n-butyl 122

Table 5 2511 l-pyrazolylJnethyl l-pyrolyljnethyl n-butyl 2512 l-imidaroly lroethyl l-pyrazolylmethyl n-butyl 2513 l-indolylmethyl l-imidazolyljnethyl n-butyl 2514 l-triazolylmethyl l-indolylmethyl n-butyl 2515 1-tetrazolylmethyl l-triazolylmethyl n-butyl 2516 2-pyridylmethyl l-tetrazolylmethyl n-butyl 2517 3-pyridylmethyl 2-pyridyljnethyl n-butyl - 2518 4-pyridylroethyl 3-pyridylmethyl n-butyl 2519 cyclohexylroethyl 4-pyridyloethy1 n-butyl 2520 2-naphthy lmethy1 cyclohexylmethyl n-butyl 2521 3-naphthylmethyl 2-naphthylmethyl n-butyl 2522 2-thiophenylmethyl 3-naphthylmethyl n-butyl 2523 4-(l-methyl) - . piperidinyl-methyl 2-thiophenylmethyl n-butyl 2524 "(3,4- »ethylenedioxyphenyl)o ethyl" 4-(l-methyl) -piperidinyl-nethyl n-butyl 2525 2-thienylmethyl "(3,4-®ethylene-dioxyphenyl)methyl" n-butyl 2526 4-biphenylmethyl 2-thienylffiethyl n-butyl 2527 pyrimidinylmethyl 4-biphenylmethyl n-butyl 2528 2-benzothiazolylmethyl pyrimidinylmethyl n-butyl 2529 2- benzothiophenylmethyl 2-benzothiazolylmethyl n-butyl 2530 2-thiomethylethyl 2- ben zoth i ophenylmethyl n-butyl 2531 2-thiomethylmethyl 2-thiometbylethyl n-butyl 2532 2-methylpropyl 2-thiomethylmethyl n-butyl 2533 2-roethylbutyl 2-methylpropyl n-butyl 2534 3-methylbutyl 2-methylbutyl n-butyl 2535 cyclopropylmethyl 3-methylbutyl n-butyl 2536 cyclobutylmethyl cyclopropyLtt>ethyl n-butyl 2537 cyclopentylmethyl cyclobutylmethyl n-butyl 2538 p-hydroxyphenyl-methyl cyclopentylmethyl n-butyl 2539 p-nitrophenyliTiethyl p-hydroxyphenyl~roethyl n-butyl 2540 p-aminophenyl-methyl p-nitrophenyl»ethyl n-butyl 2541 "4-(N,N-dimethyl-amino)phenyl-methyl" p-aminophenyl-methyl n-butyl 2542 benzyl "4-(H,N-dimethyl-amino) -phenylxnethyl" iaobutyl 2543 l-pyrolylmethyl benzyl iaobutyl 2544 l-pyrazolylmethyl l-pyrolylmethyl isobutyl 2545 l-imidazolylmethyl l-pyrazolylmethyl isobutyl 2546 l-indolylmethyl l-imidazolyljnethyl iaobutyl 2547 l-triazolylmethyl l-indolylmethyl lsobutyl 2548 l-tetrazolylmethyl l-triazolylmethyl isobutyl 2549 2-pyridylmethyl l-tetrazolylnvethyl isobutyl 2550 3-pyridylmethyl 2-pyridylmethyl isobutyl 2551 4-pyridylroethyl 3-pyridylmethyl isobutyl 2552 cyclohexylmethyl . 4-pyridyljnethyl lsobutyl 2553 2-naphthylroethyl cyclohexylmethyl iaobutyl 2554 3-naphthylmethyl 2-naphthylmethyl laobutyl 2555 2-thiophenyln»ethyl 3-naphthylmethyl iaobutyl 2556 4-(l-methyl)-piperidinyl-methyl 2-thiophenyljnethyl lsobutyl 123 LV 10096 labie ..5 2557 "(3,4- methylenedloxyphenyl)m ethyl" 4-(l-methyl)-piperidinyl-methyl Ī3obutyl 2558 2-thienylmethyl "(3,4-methylene-dioxyphenyl) methyl’' isobutyl 2559 4-biphenylmethyl 2-thienylmethyl iaobutyl 2560 pyrimidinylmethyl 4-biphenylmethyl isobutyl 2561 2-benzothiazolylinethyl pyrimidinylmethyl isobutyl 2562 2- benzothiophenylmethyl 2-benzothiazolylmethyl isobutyl 2563 2~thiomethylethyl 2- benzothiophenylmethyl isobutyl 2564 2-thiomethylmethyl 2-thiomethylethyl isobutyl 2565 2-methylpropyl 2-thiomethylmethyl isobutyl 2566 2-methylbutyl 2-methylpropyl isobutyl 2567 3-methylbutyl 2-methylbutyl isobutyl 2568 cyclopropylmethyl 3-methylbutyl isobutyl 2569 cyclobutylmethyl cyclopropylmethyl isobutyl 2570 cyclopentylmethyl cyclobutylmethyl isobutyl 2571 p-hydroxyphenyl-methyl cyclopentylmethyl isobutyl 2572 p-nitrophenylmethyl p-hydroxyphenyl-methyl isobutyl 2573 p-aminophenyl-methyl p-nitrophenylmethyl isobutyl . 2574 "4-(N,N-dimethyl-amj.no) -phenylmethyl* p-aminophenyl-iaethyl isobutyl 2575 benzyl "4-(N,N-dimethyl- amino)-phenylmethyl* 2-butyl 2576 l-pyrolylmethyl benzyl 2-butyl 2577 l-pyrazolylmethyl l-pyrolylmethyl 2-butyl 2578 l-imidazolylmethyl l-pyrazolylmethyl 2-butyl 2579 l-indolylmethyl 1- imidazolylmethy1 2-butyl 2580 1-triazolylmethyl 1-indo1ylmethy1 2-butyl 2581 l-tetrazolylmethyl l«triazolylmethyl 2-butyl 2582 2-pyridylmethyl l-tetrazolylmethyl 2-butyl 2583 3-pyridylmethyl 2-pyridylmethyl 2-butyl 2584 4-pyridylmethyl 3-pyridylmethyl 2-butyl 2585 cyclohexylmethyl 4-pyridylmethyl 2-butyl 2586 2-naphthylinethyl cyclohexylmethyl 2-butyl 2587 3-naphthylroethyL 2-naphthylmethyl 2-butyl 2588 2-thiophenylroethyl 3-naphthyljnethyl 2-butyl 2589 4-(l-methyl)-piperidinyl-methyl 2-thiophenylmethyl 2-butyl 2590 " (3,4-methylene-dioxyphenyl)roethyl" 4-(l-methyl)-piperidinyl-methyl 2-butyl 2591 2-thienylmethyl "(3,4-methylene-dioxyphenyl)methyl" 2-butyl 2592 4-biphenylmethy1 2-thienylmethyl 2-butyl 2593 pyrimidinylmethyl 4-biphenylmethyl 2-butyl 2594 2-benzothiazolylmethyl pyrimidinylmethyl 2-butyl 2595 2- benzoth iopheny lmethyl 2-benzothlazolylmethyl 2-butyl 2596 2-thiomethylethyl 2- benzothiophenylmethyl 2-butyl 2597 2-thiomethylroethyl 2-thiomethylethyl 2-butyl 2598 2-methylpropyl 2-thiomethylmethyl 2-butyl 2S99 2-methylbutyl 2-methylpropyl 2-butyl 2600 3-methylbutyl 2-methylbutyl 2-butyl 2601 cyclopropylmethyl 3-methylbutyl 2-butyl 124 labie 5 2602 cyclobutylmethyl cyclopropylinethyl 2-butyl 2603 cyclopentylmethyl cyclobutylmethyl 2-butyl 2604 p-hydroxyphenyl-methyl cyclopentylmethyl 2-butyl 2605 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-butyl 2606 p-aminophenyl-methyl p-nitrophenylmethyl 2-butyl 2607 "4- (N, N-dimethyl-amino) -phenylxnethyl" p-aminophenyl-methyl 2-butyl 2608 benzyl "4-{N,N-dimethyl-amino)phenylmethyl" •3,3- dimethallyl" 2609 1-pyroly lxoethyl benzyl •3,3- diroethallyl" 2610 l-pyrazolylmethyl 1 l-pyrolyloethyl •3,3- diavethallyl" 2611 l-imidazolylroethyl l-pyrazolylmethyl •3,3- dimethallyl" 2612 l-indolylmethyl l-imidazolylmethyl *»3# 3- dimethallyl" 2613 l-triazolylmethyl l-indolylmethyl "3,3- diinethallyl· 2614 l-tetrazolylmethyl l-triazolylmethyl "3,3- dimethallyl" 2615 2 -pyr idyJjnethyl l-tetrazolylmethyl "3,3- dimethallyl" 2616 3-pyridylmethyl 2-pyridylmethyl "3,3- dimethallyl" 2617 4-pyridylmethyl 3-pyridylmethyl •3,3- dimethallyl" 2616 cyclohexylmethyl 4-pyridylmethyl •3,3- diinethallyl" 2619 2-naphthylmethyl cyclohexylmethyl "3,3- dimethallyl" 2620 3-naphthylmethyl 2-naphthylmethyl •3,3- dimethallyl" 2621 2-thiophenylmethyl 3-naphthylmethyl •3,3- dimethallyl" 2622 4* (1- methyl)piperidinyl-methyl 2-thiophenylroethyl •3,3- dimethallyl" 2623 "(3,4- methylenedioxyphenyl)m ethyl" 4-{l- methyl)piperidinyl-methyl •3,3- dimethallyl" 2624 2-thienyl®ethyl "(3,4-roethylene-dioxyphenyl)methyl· "3,3- diroethallyl" 2625 4-biphenylmethyl 2-thienylmethyl "3,3- dimethallyl" 2626 pyrimidinyljnethyl . 4-biphenylmethyl "3,3- dimethallyl· 2627 2-benzothiazolylmethyl pyrimidinylmethyl "3,3- diroethallyl" 2628 2- benzothiophenylmethyl 2-benzothiazolylmethyl •3,3- dimethallyl" 2629 2-thiomethylethyl 2- benzothiophenylmethyl "3,3- dimethallyl* 2630 2-thiomethylmethyl 2-thiomethylethyl "3 3- dimethalļyl" 2631 2-methylpropyl 2-thlomethylmethyl "3,3- dimethallyl" t 125 LV 10096

Table S 2632 2-methylbutyl 2-methylpropyl •3,3- dimethallyl" 2633 3-methylbutyl 2-methylbutyl •3,3- dimethallyl" 2634 cyclopropylmethyl 3-methylbutyl "3,3- dimethallyl" .2635 cyclobutylmethyl cyclopropylmethyl "3,3- dimethallyl" 2636 cyclopentylmethyl cyclobutylmethyl "3,3- dimethallyl" 2637 p-hydroxyphenyl-methyl cyclopentylmethyl •3,3- dimethallyl" 2636 p-nitrophenylmethyl p-hydroxyphenyl-methyl "3,3- dimethallyl" 2639 p-aminophenyl-methyl p-nitrophenylmethyl •3,3- dimethallyl" 2640 "4-(N,N- dimethylami.no) phenylme thyl" p-aminophenyl-methyl "3,3- dimethallyl" 2641 benzyl "4-(N,N- dimethylamino)-phenyl-methyl" 3-methallyl 2642 l-pyrolylmethyl benzyl 3-methallyl 2643 l-pyrazolylmethyl l-pyrolylmethyl 3-methallyl 2644 l-imidazolylmethyl l-pyrazolyliriethyl 3-methallyl 2645 l-indolylmethyl l-imidazolylmethyl 3-methallyl 2646 l-triazolylmethyl . l-indolylmethyl 3-methallyl 2647 l-tetrazolylmethyl l-triazolylmethyl 3-methallyl 2648 2-pyridylmethyl l-tetrazolylnvethyl 3-methallyl 2649 3-pyridylroethyl 2-pyridylmethyl 3-methallyl 2650 4-pyridylmethyl 3-pyridylmethyl 3-methallyl 2651 cyclohexylmethyl 4-pyridylmethyl 3-methallyl 2652 2-naphthylmethyl cyclohexylmethyl ' 3-methallyl 2653 3-naphthylmethyl 2-naphthylmethyl 3-methallyl 2654 2-thiophenylmethyl 3-naphthylmethyl 3-methallyl 2655 4-(l-methyl)-piperidinyl-methyl 2-thiophenylmethyl 3-methallyl 2656 •(3,4- methylenedioxyphenyl)m ethyl" 4-(l- methyl)piperidinyl* methyl 3-methallyl 2657 2-thienylmethyl "(3,4-methylene-dioxyphenyl)methyl" 3-methallyl 2658 4-biphenylmethyl 2-thienylmethyl 3-methallyl 2659 pyr imidinylmethyl 4-biphenylmethyl 3-methallyl 2660 2-benzothiazolylmethyl pyrimidinylmethyl 3-methallyl 2661 2- benzothiophenylmethyl 2-benzothiazolylmethyl 3-methallyl 2662 2-thiomethylethyl 2- benzothiophenylmethyl 3-methallyl 2663 2-thiomethylmethyl 2-thiomethylethyl 3-methallyl 2664 2-methylpropyl 2-thiomethylmethyl 3-methallyl 2665 2-methylbutyl 2-methylpropyl 3-methallyl 2666 3-methylbutyl 2-methylbutyl 3-methallyl 2667 cyclopropylmethyl 3-methylbutyl 3-methallyl 2666 cyclobutylmethyl cyclopropylmethyl 3-roethallyl 2669 cyclopentylmethyl cyclobutylmethyl 3-methallyl 2670 p-hydroxyphenyl-methyl cyclopentylmethyl 3-methallyl 126 labie 5 2671 p-nitrophenylmethyl p-hydroxyphenyl-methyl 3-methallyl 2672 p-aminophenyl-methyl · p-nitrophenylmethyl 3-roethallyl 2673 •4-(H,N-di®ethyl-amino)-phenyl-methyl" p-aminophenyl-methyl 3-methallyl 2674 benzyl "4-(N,N-dimethyl-amino)phenylmethyl" 2-methallyl 2675 l-pyrolylmethyl benzyl 2-methallyl 2676 l-pyrazolylmethyl l-pyrolylmethyl 2-methallyl 2677 l-imidazolylmethyl l-pyrazolylmethyl 2-methallyl 2678 l-indolylmethyl 1-imidazoly lmethy1 2-methallyl 2679 l-triazolylmethyl l-indolylmethyl 2-methallyl 2680 . l-tetrazolylmethyl l-triazolylmethyl 2-methallyl 2681 2-pyridylmethyl l-tetrazolylroethyl 2-methallyl 2682 3-pyridylmethyl 2-pyridylmethy1 2-roethallyl 2683 4-pyridylmethyl 3-py r i dy line t hy 1 2-methallyl 2684 cyclohexylmethyl 4-pyridylmethyl 2-methallyl 2685 2-naphthyl»ethyl cyclohexylmethyl 2-methallyl 2686 3-naphthylmethyl 2-naphthylmethyl 2-roethallyl 2687 2-thlophenylmethyl 3-naphthyJjnethyl 2-methallyl 2688 4- (1- methyl)piperidinyl- methyl 2-thiophenylmethyl 2-methallyl 2689 " {3,4-methylene-dioxyphenyl) methyl" 4-(l-methyl)-piperidinyl-methyl 2-methallyl 2690 2-thienylmethyl * (3/4-methylene-dioxyphenyl)methyl" 2-methallyl 2691 4-biphenylmethyl 2-thienylmethyl 2-methallyl 2692 pyrinu.dinylmethyl 4-biphenylmethyl 2-methallyl 2693 2-benzothiazolyljnethyl pyrimidinylmethyl 2-roethallyl 2694 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2-methallyl 2695 2-thiomethylethyl 2- benzothiophenylmethyl 2-methallyl 2696 2-thiomethylmethyl 2-thiomethylethyl 2-methallyl 2697 2-methylpropyl 2 -thionvethylmethyl 2-methallyl 2698 2-methylbutyl 2-methylpropyl 2-methallyl 2699 3-methylbutyl 2-methylbutyl 2-methallyl 2700 cyclopropylmethyl 3-methylbutyl 2-:nethallyl 2701 cyclobutylmethyl cyc1opropylmethy1 2-roethallyl 2702 cyclopentylmethyl cyclobutylmethyl 2-methallyl 2703 p-hydroxyphenyl-methyl cyclopentylmethyl 2-methallyl 2704 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-methallyl 2705 p-a^iinophenyl-methyl p-nit rophenylmethyl 2-methallyl 2706 *4-(N,N-dimethyl-amino)-phenylmethyl" p-aminophenyl-roethyl 2-roethallyl 2707 benzyl "4-{N/K-dimethyl-amino)-phenylmethyl" 2-propyl 2708 l-pyrolylmethyl benzyl 2-propyl 2709 l-pyrazolylmethyl l-pyrolylmethyl 2-propyl 2710 l-imidazolylmethyl l-pyrazolylmethyl 2-propyl 2711 l-indolylmethyl l-imidazolylmethyl 2-propyl 2712 l-triazolylmethyl l-indolylmethyl 2-propyl 2713 l-tetrazolylmethyl l-triazolylroethyl 2-propyl 2714 2-pyridylmethyl l-tetrazolylmethyl 2-propyl 2715 3-pyridylmethyl 2-pyridylmethyl 2-propyl 2716 4-pyridylmethyl 3-pyridylmethy1 2-propyl 2717 cyclohexylmethyl 4-pyridylmethyl 2-propyl 127 labie .,,5 LV 10096 2718 2-naphthylmethy1 cyclohexylmethyl 2-propyl 2719 3-naphthylmethyl 2-naphthylmethyl 2-propyl 2720 2-th iophenylme t hy1 3-naphthylmethyl 2-propyl 2721 4- (1- 2-thiophenylmethyl 2-propyl 2722 methyl) piperidinyl-jnethyl "(3,4-methylene- 4-(l-methyl)- 2-propyl dioxyphenyl)methyl" piperidinyl-methyl 2723 2-thienylmethyl " (3,4-methylene- 2-propyl 2724 4-biphenylmethyl dioxyphenyl)methyl" 2-thienylmethyl 2-propyl 2725 pyrimidinylmethyl 4-biphenylmethyl 2-propyl 272$ 2-benzothiazolylmethyl pyrimidinylmethyl 2-propyl 2727 2- 2-benzothiazolylmethyl 2-propyl 2728 benzothiophenylmethyl 2-thiomethylethyl 2- 2-propyl 2729 2-thiomethylmethyl benzothiophenylroethyl -2-thiomethylethyl 2-propyl 2730 2-methylpropyl 2-thiomethylmethyl 2-propyl 2731 2-methylbutyl 2-methylpropyl 2-propyl 2732 3-methylbutyl 2-methylbutyl 2-propyl 2733 cyclopropylroethyl 3-methylbutyl 2-propyl 2734 cyc1obutylmethyl cyclopropylmethyl 2-propyl 2735 cyclopentylnvethyl cyclobutylmethyl 2-propyl 2736 p-hydroxyphenyl-methyl cyc1opentylmethy1 2-propyl 2737 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-propyl 2738 p-aminophenyl-methyl p-nitrophenylmethyl 2-propyl 2739 "4-(N,N-dimethyl- p-aminophenyl-methyl 2-propyl 2740 ami.no)-phenylmethyl" benzyl "4-(N,N-dimethyl- cyclopropyl 2741 1-pyrolylmethyl amino)phenylmethyl· benzyl cyclopropyl 2742 l-pyrazolylmethyl l-pyrolylmethyl cyclopropyl 2743 l-imidazolylmethyl l-pyrazolylmethyl cyclopropyl 2744 l-indolylroethyl l-imidazolylmethyl cyclopropyl 2745 l-triazolylmethyl l-indolylavethyl cyclopropyl 2746 l-tetrazolylmethyl l*triazolylmethyl cyclopropyl 2747 2-pyridylmethyl l-tetrazolylmethyl cyclopropyl 2748 3-pyridylmethyl 2-pyridylmethyl cyclopropyl 2749 4-pyridylmethyl 3-pyridylmethyl cyclopropyl 2750 cyclohexylmethyl 4-pyridylmethyl cyclopropyl 2751 2-naphthy lmethy1 cyclohexylmethyl cyclopropyl 2752 3-naphthylmethyl 2-naphthylmethyl cyclopropyl 2753 2-thiophenylmethyl 3-naphthylmethyl cyclopropyl 2754 4-(l-methyl)- 2-thiophenylmethyl cyclopropyl 2755 piperidinyl-methyl * (3,4-inethylene- 4-(l-methyl)- cyclopropyl 2756 dioxyphenyl) methyl* 2-thienylmethyl piperidinyl-methyl "(3,4- cyclopropyl 2757 4-biphenylmethyl methylenedioxyphenyl)m ethyl" 2-thienylmethyl cyclopropyl 2758 pyrimidinylmethyl 4-biphenylmethyl cyclopropyl 2759 2-benzothiazolylmethyl pyrimidinylmethyl cyclopropyl 2760 2- 2-benzothiazolylmethyl cyclopropyl benzothiophenylmethyl 128

Jable 5 2-thiomethylethyl 2- cyclopropyl 2-thiomethylmethyl benzothiophenylmethyl 2-thiomethylethyl cyclopropyl 2-methylpropyl .2-thiomethylmethyl cyclopropyl 2-methylbutyl 2-methylpropyl cyclopropyl 3-methylbutyl 2-methylbutyl cyclopropyl cyclopropylmethyl 3-methylbutyl cyclopropyl cyc lobutylmethyl cyclopropylmethyl cyclopropyl cyc lopentylmethyl cyclobutylmethyl cyclopropyl p-hydroxyphenyl-»ethyl cyclopentylmethyl cyclopropyl p-nitrophenylmethyl p-hydroxyphenyl-methyl cyclopropyl p-aminophenyl-methyl •4-(N,N- p-nitrophenylmethyl cyclopropyl p-aminophenyl-methyl cyclopropyl dimethylarai.no) phenylme thyl" benzyl "4-{N,N- cyclopropylmet dimethylamino) phenylme hyl l-pyrolylmethyl thyl" benzyl cyclopropylmet l-pyrazolylmethyl l-pyrolylmethyl hyl cyclopropylmet l-imidazolylmethyl l-pyrazolylmethyl hyl cyclopropylmet l-indolylmethyl l-imidazolylmethyl hyl cyclopropylmet l-tria2olyLnethyl l-indolylmethyl hyl cyclopropylmet l-tetrazolylmethyl 1*triazolylmethyl hyl cyclopropylmet 2-pyridylmethyl l-tetrazolylraethyl hyl cyclopropylmet 3-pyridylmethyl 2-pyridylmethyl hyl cyclopropylmet 4-pyridylmethy1 3-pyridylmethyl hyl cyclopropylmet hyl cyclohexylmethyl 4-pyridylmethyl cyclopropylmet 2-naphthylmethyl cyclohexylmethyl hyl cyclopropylmet 3-naphthylraethyl 2-naphthylmethyl hyl cyclopropylmet 2-thiophenylmethyl 3-naphthylmethyl hyl cyclopropylmet 4-(1- 2-thiophenylmethyl hyl cyclopropylmet methyl)piperidinyl- hyl methyl "(3,4- 4- (1- cyclopropylmet nvethylenedioxyphenyl) m methyl)piperidinyl- hyl ethyl" methyl 2-thienylmethyl "(3,4- cyclopropylmec methylenedioxyphenyl) a hyl ethyl" 4-biphenylmethyl 2-thienylmethyl ; cyclopropylnet pyrimidinylmethyl 4-biphenylmethyl : hyl cyclopropyīm*t hyl 129 LV 10096 labie 5 2-benzothiazolylmethyl pyrimidinylinethyl cyclopropylmet hyl 2- benzothiophenylmethyl 2-benzothiazolylmethyl cyclopropylmet hyl 2-thiomethylethyl 2- benzothiopheņylmethyl cyclopropylmet hyl 2-thiomethylmethyl 2-thiomethylethyl cyclopropylmet hyl 2-methylpropyl 2-thiomethylmethyl cyclopropylmet hyl 2-methylbutyl 2-methylpropyl cyclopropylmet hyl 3-oethylbutyl 2-methylbutyl cyclopropylmet hyl cyclopropylmethyl 3-methylbutyl cyclopropylmet hyl cyclobutylmethyl cyclopropylmethyl cyclopropylmet hyl cyclopentylmethyl cyclobutylmethyl cyclopropylinet hyl p-hydroxyphenyl-methyl cyclopentylmethyl cyclopropylmet hyl p-nitrophenylmethyl p-hydroxyphenyl-methyl cyclopropylmet hyl p-aminophenyl-methyl p-nitrophenylmethyl cyclopropylmet hyl "4-(N,N- diaethylamino) phenylme thyl" p-aminophenyl-methyl cyclopropylroet hyl benzyl P4-(N,N- dimethylamino)phenylae thyl* n-pentyl l-pyrolylmethyl benzyl n-pentyl l-pyrazolylmethyl l-pyrolylmethyl n-pentyl l-imidazolylmethyl 1-pyrazolylroethy1 n-pentyl l-indolylmethyl 1-imidazolylmethy1 n-pentyl l-triazolylmethyl l-indolylroethyl n-pentyl 1-tet razolyl»ethyl 1-t r ia zolylmethy1 n-pentyl 2-pyridylmethyl l-tetrazolylmethyl n-pentyl 3-pyridylmethyl 2-pyridylmethyl n-pentyl 4-pyridylmethyl 3-pyridylmethyl ,n-pentyl cyclohexylmethyl 4-pyridylmethyl n-pentyl 2-naphthy lmethyl cyclohexylmethyl n-pentyl 3-naphthylmethyl 2-naphthylmethyl n-pentyl 2-thiophenylmethyl 3-naphthylmethyl n-pentyl 4-(1- methyl)piperidinyl-inethyl 2-thiophenylmethyl n-pentyl "(3,4- methylenedioxyphenyl) m ethyl" 4-{l- methyl)piperidinyl-methyl n-pentyl 2-thienylmethy1 -<3,4- methylenedioxyphenyl)m ethyl* n-pentyl 4-biphenylmethyl 2-thienylmethyl n-pentyl pytimidinylmethyl 4-biphenylmethyl n-pentyl 2-benzothiazolylmethyl pyrimidinylmethyl n-pentyl 130 labie 5 2826 2- benzothiophenylnvethyl 2-benzothiazolylxnethyl n-pentyl 2827 2-thiomethylethyl 2- benzothiophenylmethyl n-pentyl 2828 2-thiomethylmethyl 2-thiomethylethyl n-pentyl 2829 2-methylpropyl 2-thiomethylmethyl n-pentyl 2830 2-iaethylbutyl 2-rnethylpropyl n-pentyl '2831 3-methylbutyl 2-inethylbutyl n-pentyl 2832 cyclopropylmethyl 3-methylbutyl n-pentyl 2833 cyclobutylmethyl cyclopropylmethyl n-pentyl 2834 cyclopentylmethyl cyc1obutylmethyl n-pentyl 2835 p-hydroxyphenyl-methyl cyclopentylmethyl n-pentyl 2636 p-nitrophenylmethyl p-hydroxyphenyl-roethyl n-pentyl 2837 p-aminophenyl-methyl p-nit rophenylmethyl n-pentyl 2838 "4-(N,N- dimethylamino) phenylme thyl" p-aminophenyl-ttethyl n-pentyl 2839 benzyl *4-(N,N- diroethylamino)phenylme thyl" 2-pentyl 2840 l-pyrolylmethyl benzyl 2-pentyl 2841 l-pyrazolylmethyl l-pyrolylmethyl 2-pentyl 2842 l-imidazolylmethyl l-pyrazolylmethyl 2-pentyl 2843 l-indolylmethyl 1 - imi da z ο 1 y lme t hyl 2-pentyl 2844 l-triazolylmethyl l-indolylmethyl 2-pentyl 2845 l-tetrazolylmethyl l-triazolylmethyl 2-pentyl 2846 2-pyridylmethyl l-tetrazolylmethyl 2-pentyl 2847 3-pyridylmethyl 2-pyridylmethyl 2-pentyl 2848 4-pyridylmethyl 3-pyridylmethyl 2-pentyl 2849 cyclohexylmethyl 4-pyridylmethyl 2-pentyl 2850 2-naphthylmethyl cyclohexylmethyl 2-pentyl 2851 3-naphthylmethyl 2-naphthylmethyl 2-pentyl 2852 2-thiophenylmethyl 3-naphthylmethyl 2-pentyl 2853 4-(l- methyl)piperidinyl-methyl 2-th iophenylmethyl 2-pentyl 2854 "(3,4- methylenedioxyphenyl)m ethyl" 4-(1- methyl)piperidinyl-methyl 2-pentyl 2855 2-thienylroethyl - (3,4- methylenedioxyphenyl)m ethyl* 2-pentyl 2856 4-biphenylmethyl 2-thienylmethyl 2-pentyl 2857 pyrimidinylmethyl 4-biphenylmethyl 2-pentyl 2858 2-benzothiazolylmethyl pyrimidinylmethyl 2-pentyl 2859 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2-pentyl 2860 2-thiomethylethyl 2- benzothlophenylnethyl 2-pentyl 2861 2-thiomethylnvethyl 2-thiomethylethyl 2-pentyl 2862 2-methylpropyl 2-thiomethylmethyl 2-pentyl 2863 2-methylbutyl 2-methylpropyl 2-pentyl 2864 3-methylbutyl 2-methylbutyl 2-pentyl 2865 cyclopropylmethyl 3-methylbutyl 2-pentyl 2866 cyclobutylmethyl cyclopropylmethyl 2-pentyl 2867 cyclopentylmethyl cyclobutylmethyl 2-pentyl 2868 p-hydroxyphenyl-methyl cyclopentylmethyl 2-pentyl 131 LV 10096 labie 5 2869 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-pentyl 2870 p-aminophenyl-methyl p-nitrophenylmethyl 2-pentyl 2871 *4-(N,N- dimethylamino) phenylme thyl" p-aminophenyl-methyl 2-pentyl 2872 benzyl "4-(N,N- diinethylamino) phenylme thyl" 3-pentyl 2873 l-pyrolylmethyl benzyl 3-pentyl 2874 l-pyrazolylmethyl l-pyrolylmethyl 3-pentyl 2875 1-imida zolylroethyl 1-pyrazolylmethyl 3-pentyl 2876 l-indolylmethyl l-imidazolylmethyl 3-pentyl 2877 l-triazolylmethyl l-indolylmethyl 3-pentyl 2678 1 -tet ra zolylmethyl l-triazolylmethyl 3-pentyl 2879 2-pyridylmethyl l-tetrazolylmethyl 3-pentyl 2880 3-pyridylmethyl 2-pyridylmethyl 3-pentyl 2881 4-pyridylmethyl 3-pyridylroethyl 3-pentyl 2882 cyclohexylmethyl 4-pyridylmethyl 3-pentyl 2883 2-naphthylroethyl cyclohexylmethyl 3-pentyl 2884 3-naphthylroethyl 2-naphthylmethyl 3-pentyl 2685 2-thiophenylmethyl 3-naphthylmethyl 3-pentyl 2886 4-(l- methyl)piperidinyl- methyl 2-thiophenylmethyl 3-pentyl 2887 "(3,4- methylenedioxyphenyl)m 4-(l- methyl)piperidinyl- 3-pentyl ethyl" methyl 2888 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" 3-pentyl 2889 4-biphenylmethyl 2-thienylmethyl 3-pentyl 2890 pyrimidinylmethyl 4-biphenylmethyl 3-pentyl 2891 . 2-benzothiazolylmethyl pyrimidinylmethyl 3-pentyl 2892 2- benzothiophenyl»ethyl 2-benzothiazolylmethyl 3-pentyl 2893 2-thiomethylethyl 2- benzothiophenylmethyl 3-pentyl 2894 2-thioroethylmethyl 2-thiomethylethyl 3-pentyl 2695 2-methylpropyl 2-thiomethylmethyl 3-pentyl 2896 2-methylbutyl 2-methylpropyl 3-pentyl 2897 3-methylbutyl 2-methylbutyl 3-pentyl 2898 cyclopropylmethyl 3-methylbutyl 3-pentyl 2899 cyclobutylmethyl cyclopropylmethyl 3-pentyl 2900 cyclopentylmethyl cyclobutylmethyl 3-pentyl 2901 p-hydroxyphenyl-jnethyl cyclopentylmethyl 3-pent'yl 2902 p-n it rophenylmethyl p-hydroxyphenyl-methyl 3-pentyl 2903 p-aminophenyl-methyl p-nit rophenylmethyl 3-pentyl 2904 "4-(N,N- dimethylamino) phenylme thyl" p-aminophenyl-roethyl 3-pentyl 2905 benzyl "4-(N,N- dimethylamino) phenylme thyl" 3-methylbutyl 2906 l-pyrolylmethyl benzyl 3-methylbutyl 2907 l-pyrazolylmethyl l-pyrolylmethyl 3-methylbutyl 2908 1-imida zolylmethyl l-pyrazolylmethyl 3-methylbutyl 2909 l-indolylmethyl l-imidazolylroethyl 3-methylbutyl 132 132 Iflblg-S l-indolylmethyl l-triazolylroethyl 1- tetrazolylnvethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylmethyl l-triazolylmethyl 1- tet ra zolylmethyl 2- pyridylmethyl 3- pyridylroethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylroethyl 2 -1 h i oph enylxne t hy 1 4- (1- methyl)piperidinyl- ®ethyl -(3,4- methylenedioxyphenyl)m ethyl" 2-thienylaethyl 4-biphenylroethyl pyriīnidinyl»ethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylJnethyl cyclopentylfr»ethyl p-hydroxyphenyl-methyl p-nit rophenylmethyl p-aminophenyl-methyl "4-(N,N- dimethylamino)phenylme thyl· benzyl l-pyrolybnethyl 1-pyrazolylmethyl l-imidazolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolyljnethyl 2- pyridyl»ethyl 3- pyridylioethyl 4- pyridylmethy1 cyclohexylzaethyl 2- naphthylmethyl 3- naphthy lmethy1 2-thiophenylmethyl 4- (1- methyl)pip«ridinyl-methyl 4- (1- methyl)piperidinyl- methyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethyl 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- n>ethylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylwethyl cyclopentylinethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl "4-(N,N- dimethylamino) pheny lme thyl" benzyl l-pyrolylmethyl l-pyrazolylmethyl l-imidazolylmethyl l-indolylmethyl l-trlazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylroethyl cyclohexylmethyl 2- naphthylroethyl 3- naphthy lmethyl 2-thiophenylmethyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbūtyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-roethylbutyl 3-methylbutyl 3-roethylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 3-methylbutyl 2-methylbutyl 2-methylbutyl 2-methylbutyl 2-roethylbutyl 2-methylbutyl 2-methylbutyl 2-methylbutyl 2-methylbutyl 2-roethylbutyl 2-methylbutyl 2-methylbutyl 2-jnethylbutyl 2-nvethylbutyl 2-methylbutyl 2-methylbutyl 133 LV 10096

Tablfi 5 "(3,4- 4 — (1— 2-methylbutyl methylenedioxyphenyl)m . methyl)piperidinyl- ethyl" methyl 2-thienyljnethyl "(3,4- methylenedioxyphenyl)m ethyl" 2-methylbutyl 4-biphenylmethyl 2-thienylmethyl 2-methylbutyl pyrimidinylmethyl 4-biphenylir»ethyl 2-oethylbutyl 2-benzothiazolyljnethyl pyriniidinylxnethyl 2-oethylbutyl 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2-methylbutyl 2-thiomethylethyl 2- 2-methylbutyl • benzothiophenylmethyl 2-thiomethylmethyl 2-thioroethylethyl 2-methylbutyl 2-methylpropyl 2-thiomethylmethyl 2-methylbutyl 2-methylbutyl 2-roethylpropyl 2-methylbutyl 3-methylbutyl 2-methylbutyl 2-methylbutyl cyclopropylmethyl 3-roethylbutyl 2-methylbutyl cyclobutylmethyl cyclopropylmethyl 2-methylbutyl cyclopentylmethyl cyclobutylmethyl 2-methylbutyl p-hydroxypheny 1 -iaethyl cyclopentylmethyl 2-rnethylbutyl p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-methylbutyl p-andnophenyl-jnethyl p-nitrophenylroethyl 2-methylbutyl "4-(N,N- p-aminophenyl-methyl 2-methylbutyl dimethylamino) phenylme thyl" benzyl "4-(N,N- dimethylami.no)phenylme thyl* propargyl l-pyrolylmethyl benzyl propargyl l-pyrazolylroethyl l-pyrolylmethyl propargyl l-imidazolylmethyl l-pyrazolylmethyl propargyl l-indolylmethyl l-imidazolylmethyl propargyl l-triazolylmethyl l-indolylmethyl propargyl l-tetrazolyl®ethyl l-triazolylmethyl propargyl 2-pyridylmethyl l-tetrazolylmethyl propargyl 3-pyridylmethyl 2-pyridylmethyl propargyl 4-pyridylmethyl 3-pyridylmethyl propargyl cyclohexylmethyl 4-pyridylmethyl propargyl 2-naphthylroethyl cyclohexylmethyl propargyl 3-naphthylm«thyl 2-naphthylmethyl propargyl 2-thiophenylmethyl 3-naphthylmethyl propargyl 4-(1- 2-thiophenylmethyl propargyl methyl)piperidinyl- methyl "(3,4- 4-(1- propargyl methylenedioxyphenyl)m methyl)piperidinyl- ethyl* methyl 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl* propargyl 4-biphenylmethyl 2-thienylmethyl propargyl pyrimidinylmethyl 4-biphenylmethyl propargyl 2-benzothiazolylinethyl pyrimidinylmethyl propargyl 2- 2-benzothiazolylmethyl propargyl benzothi©phenyLnethyl 134 labie 2-thiomethylethyl 2-thiomethyLnethyl 2-methylpropyl 2- methylbutyl 3- roethylbutyl cyclopropylraethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-n it rophenylmethyl p-aminophenyl-methyl *4-(N,N- dimethylamlno) phenylne thyl- benzyl l-pyrolylmethyl l-pyrazolylmethyl l-imidazolylmethyl l-indolylmethyl l-triazolyljnethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylirvethyl 4- (1- methyl)pip«ridinyl-methyl "(3,4- methylenedioxyphenyl)m ethyl· 2-thienylmethyl 4-biphenylmethyl pyrimidinylmethyl 2 -benzothiazolylmethy1 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- roethylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nit rophenylmethyl p-aminophenyl-methyl 2- benzothlophenylmethy1 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylroethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nit rophenylmethyl p-ami nopheny1-methy1 •4-{N,N- dimethylamino)phenylme thyl" benzyl l-pyrolylmethyl l-pyrazolylmethyl l-imidazolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethy1 3- pyridylmethyl 4- pyridylmethyl cyclohexylroethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylroethyl 4-(l- methyl)piperidinyl- tnethyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethyl 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thionvethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylroethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nit rophenylroethyl 135 LV 10096 labie ..3 *4-(N,N- p-aminophenyl-methyl cyclobutyl dimethylami.no)phenylme thyl" benzyl "4-(N,N- cyclobutylmeth dimethylamino) phenylme thyl" yi l-pyrolylmethyl benzyl cyclobutylmeth yi l-pyrazolyl®ethyl l-pyrolylmethyl cyclobutylmeth yi l-imidazolylmethyl l-pyrazolylmethyl cyclobutylmeth yi cyclobutylmeth yi l-indolylmethyl ' l-imidazolylmethyl l-triazolylmethyl l-indolylmethyl cyclobutylmeth yi 1-t et ra zolyl®ethy1 l-triazolylmethyl cyclobutylroeth yi 2-py ridy linethy 1 l-tetrazolylmethyl cyclobutylmeth yi 3-pyridylmethyl 2-pyridy lmethy1 cyclob«tylmeth yi 4-pyridylaethy1 3-pyridylmethyl cyclobutylmeth yi cyclohexylmethyl 4-pyridylmethyl cyclobutylmeth yi 2-naphthylmethyl cyclohexylmethyl cyclobutylmeth yi cyclobutylmeth yi cyclobutylmeth yi 3-naphthylmethyl 2-naphthylmethyl 2-thiophenylme thyl 3-naphthylmethyl 4-(1- 2-thiophenylmethyl cyclobutylmeth methyl)piperidinyl-methyl yi "(3,4- 4-(1- cyclobutylmeth methylenedioxyphenyl)m methyl) piperidinyl- yi ethyl" methyl 2-thienylmethyl "(3,4- cyclobutylmeth methylenedioxyphenyl)m ethyl" yi 4-biphenylmethyl 2-thienylmethyl cyclobutylmeth yi cyclobutylmeth yi cyclobutylmeth yi pyrimidinylmethyl 4-biphenylmethyl 2-benzothiazolylmethyl pyrimidinylmethyl 2- 2-benzothiazolylmethyl cyclobutylmeth benzothiophenylmethyl yi 2-thiomethylethyl 2- cyclobutylmeth benzothiophenylmethyl yi 2 -thiomethyljnethyl 2-thiomethylethyl cyclobutylmeth yi cyclobutylmeth yi 2-methylpropyl 2-thiomethylmethyl 2-inethylbutyl 2-methylpropyl cydobutylmeth yi 136

Table 5 3062 3-methylbutyl 2-methylbutyl cyclobutylmeth yi cyclobutylroeth yi cyclobutylmeth yi cyclobutylmeth yi cyclobutylineth yi cyclobutylmeth yi cyclobutylmeth yi cyclobutylmeth yi 3063 cyclopropylmethyl 3-methylbutyl 3064 cyclobutylnvethyl cyclopropylmethyl 3065 cyclopentylnvethyl cyclobutylmethyl 3066 p-hydroxyphenyl-me£hyl cyclopentylmethyl 3067 p-nitrophenylmethyl p-hydroxyphenyl-methyl 3068 p-aminophenyl-methyl . p-nitrophenylmethyl 3069 "4-(N,N- diroethylamJ.no) phenylme thyl" p-aminophenyl-methyl 3070 benzyl *4-(N,N- diroethylamino) phenylme thyl" cydopentyl 3071 l-pyrolylmethyl benzyl cyclopentyl 3072 l-pyrazolylmethyl l-pyrolylroethyl cyclopentyl 3073 l-imidazolylroethyl l-pyrazolylmethyl cyclopentyl 3074 l-indolylmethyl l-imidazolylmethyl cydopentyl 3075 l-triazolylroethyl l-indolylmethyl cyclopentyl 3076 l-tetrazolylmethyl l-triazolylmethyl cydopentyl 3077 2-pyridylroethyl l-tetrazolylroethyl cydopentyl 3078 3-pyridylmethyl 2-pyridylroethyl cydopentyl 3079 4-pyridylmethyl 3-pyridylroethyl cyclopentyl 3080 cyclohexylmethyl 4-pyridylmethyl cyclopentyl 3081 2-naphthylroethyl cyclohexylmethyl cyclopentyl 3082 3-naphthylmethyl 2-naphthylmethyl cydopentyl 3083 2-thiophenylmethyl 3-naphthylmethyl cyclopentyl 3084 4-a- methyl)piperidinyl- methyl 2-thiophenylroethyl cyclopentyl 3085 "(3,4- methylenedioxyphenyl)m ethyl" 4-a- methyl)piperidinyl-methyl cyclopentyl 3086 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" cyclopentyl 3087 . 4-biphenylroethyl 2-thienylmethyl cyclopentyl 3088 pyzimidinylmethyl 4-biphenylmethyl cydopentyl 3089 2-benzothiazolylmethyl pyrimidinylmethy1 cyclopentyl 3090 2- benzothiophenylmethyl 2-benzothiazolylmethyl cyclopentyl 3091 2-thiomethylethyl 2- benzothiophenylroethyl cyclopentyl 3092 2-thiomethylmethyl 2-thiomethylethyl cyclopentyl 3093 2-methylpropyl 2-thiomethylmethyl cyclopentyl 3094 2-methylbutyl 2-methylpropyl cyclopentyl 3095 3-methylbutyl 2-methylbutyl cyclopentyl 3096 cyclopropylmethyl 3-methylbutyl cydopentyl 3097 cyclobutylraethyl cyclopropylmethyl cyclopentyl 3098 cyclopentylmethyl cyclobutylmethyl cydopentyl 3099 p-hydroxyphenyl-methyl cyclopentylroethyl cyclopentyl 137 LV 10096

Table 5 3100 p-nitrophenylwethyr p-hydroxyphenyl-roethyl cyclopentyl 3101 p-aminophenyl-methyl p-nitrophenylmethyl cyclopentyl 3102 •4-<N,N- diftethylaffli.no) phenylme thyl" p-atninophenyl-inethyl cyclopentyi 3103 benzyl "4-(N/N- cyclopentylftet dimethylamino)phenylme thyl" hyl 3104 l-pyrolylmethyr benzyl cyclopentylmet hyl 3105 l-pyrazolylmethyl l-pyrolylmethyl cyclopentylmet hyl 3106 l-imidazolylmethyl l-pyrazolylmethyl cyclopentylmet hyl 3107 l-indolylmethyl l-imidazolylmethyl cyclopentylmet hyl 3108 l-triazolylmethyl l-indolylmethyl cyclopentylftet hyl 3109 l-tetrazolylmethyl l-triazolylmethyl cyclopentylmet hyl 3110 2-pyridylmethyl l-tetrazolylmethyl cyclopentylftet hyl 3111 3-pyridyljnethyl 2-pyridylftethyl cyclopentylmet hyl 3112 4-pytidylmethyl 3-pyridylmethyl cyclopentylroet hyl 3113 cyc1ohexylmethy1 4-pyridylmethyl cyclopentylroet hyl 3114 2-naphthylmethy1 cyclohexylftethyl cyclopentylroet hyl 3115 3-naphthylmethyl 2-naphthylftethyl cyclopentylftet hyl 3116 2-thiophenylmethyl 3-naphthylmethyl cyclopentylmet hyl 3117 4-(l- methyl)piperidinyl- ftethyl 2-thiophenylmethyl cyclopentylftet hyl 3118 * (3,4- 4-(l- cyclopentylftet methylenedioxyphenyl)m methyl)piperidinyl- hyl ethyl" methyl 3119 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" cyclopentylmet hyl 3120 4-biphenylmethyl 2-thienylmethyl cyclopentylmet hyl 3121 py r laid iny lme t hy 1 4-biphenylmethyl cyclopentylmet hyl 3122 2-benzothiazolylmethyl pyrimidinylmethyl cyclopentylmet hyl 3123 2- 2-benzothiazolylmethyl cyclopentylmet benzothiophenylmethyl hyl 3124 2-thiomethylethyl 2- benzothiophenylftethyl cyclopentylftet hyl 3125 2-thiomethylmethyl 2-thiomethylethyl cyclopentylmet hyl 3126 2-methylpropyl 2-thiomethylmethyl cyclopentylmet hyl 138 3127 lablfi-S 2-methylbutyl 2-methylpropyl cyclopentylmet 3128 3-methylbutyl 2-methylbutyl hyl cyclopentylmet 3129 cyclopropylmethyl 3-methylbutyl hyl cyclopentyLnet 3130 cyclobutylroethyl cyclopropylrnethyl hyl cyclopentylmet 3131 cyclopentylmethyl cyclobutyl»ethyl hyl cyclopentylmet 3132 p-hydroxyphenyl-methyl cyclopentylnethyl hyl cyclopentylwet 3133 • p-nit rophenylmethyl p-hydroxyphenyl-methyl hyl cyclopentylmet 3134 p-aminophenyl-methyl p-nitrophenylmethyl hyl cyclopentylmet 3135 "4-(N,N- p-aminophenyl-methyl hyl cyclopentylmet 3136 dimethylamino)phenylme thyl" benzyl "4-(N,N- hyl l-hexyl 3137 l-pyrolylmethyl dimethylamino) phenylme thyl" benzyl l-hexyl 3138 l-pyrazolylmethyl l-pyrolylmethyl l-hexyl 3139 l-imidazolylmethyl l-pyrazolylmethyl l-hexyl 3140 l-indolylmethyl l-imidazolylroethyl l-hexyl 3141 l-triazolylmethyl l-indolylmethyl l-hexyl 3142 1-tetrazolylmethyl l-triazolylinethyl i-hexyl 3143 2-pyridylmethyl l-tetrazolyl®ethyl l-hexyl 3144 3-pyridylmethyl 2-pyridybnethyl l-hexyl 3145 4-pyridylmethyl 3-pyridylmethy1 l-hexyl 3146 cyclohexylmethyl 4-pyridylmethyl l-h«xyl 3147 2-naphthyljnethyl cyclohexyln»ethyl l-hexyl 3148 3-naphthylmethyl 2-naphthylmethyl l-hexyl 3149 2-thiophenylmethyl 3-naphthylmethyl l-hexyl 3150 4-(l- 2-thiophenylmethyl l-hexyl 3151 methyl)piperidinyl- jnethyl "<3,4- 4-(l- l-hexyl 3152 methylenedioxyphenyl)m ethyl" 2-thienyln>ethyl inethyl)piperidinyl-roethyl "(3/4- l-hexyl 3153 4-bļphenylmethy1 roethylenedioxypbenyl)a ethyl" 2-thienylroethyl l-hexyl 3154 pyrixrddinyljnethyl 4-biphenylmethyl l-hexyl 3155 2-benzothiazolylmethyl pyrimidinylmethyl l-hexyl 3156 2- 2-benzothiazolylmethyl l-hexyl 3157 benzothiophenylmethyl 2-thionvethylethyl 2- l-hexyl 3158 2-thiomethylmethyl benzothiophenylmethyl 2-thiomethylethyl l-hexyl 3159 2-methylpropyl 2-thiomethylmethyl l-hexyl 3160 2-methylbutyl 2-methylpropyl l-hexyl 3161 3-methylbutyl 2-methylbutyl l-hexyl 3162 cyclopropylxnethyl 3-methylbutyl l-hexyl 3163 cyclobutylmethyl cyclopropylmethyl l-hexyl 139labie 5 cyclopentylmethyl p-hydr oxyphenyl -methyl p-nitrophenylmethyl p-aminophenyl-methyl "4-(N,N- dimethylamino) phenylxne thyl" benzyl cyclobutylmethyl 'cyclopentylmethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl LV 10096 l-hexyl l-hexyl l-hexyl l-hexyl l-hexyl l-pyrolylxnethyl l-pyra2olylmethyl 1 - imi da z o ly lme t hy 1 l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylmethyl 4- (l- methyl)piperidinyl- methyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethyl "4-(N,N- dimethylamino) phenylme thyl" benzyl l-pyrolylmethyl l-pyrazolylmethyl 1-imi dazolylmethyl l-indolyl®ethyl l-triazolylmethyi 1- tetrazolylmethyl 2- pyridylmethy1 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethy1 2-thiophenylmethyl 4-methylpentyl 4-methylpentyl 4-®ethylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- roethylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nit rophenylmethyl p- aminopheny 1-me t hy 1 "4-(W,N- dimethylamino) phenylme thyl" benzyl 4-(l- methyl)pip«ridinyl- methyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethyl 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thio®ethylethyl 2-thioroethylmethyl 2 -methy lpropy 1 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylroethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl 4-methylp«ntyl 4-methylp«ntyl 4-methylpentyl 4-jnethylpentyl 4-methylpentyl 4-methylp«ntyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl 4-methylpentyl l-pyrolylroethyl l-pyrazolylmethyl "4-(N,K- dimethylamino)phenylme thyl" benzyl 1 -py rolylmethyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 140 140 Table 5 1-imidazolylmethyl 1 -indoly lnvethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthyl®ethyl 3- naphthylmethyl 2-thiophenylmethyl 4- <l- methyl)piperidinyl- »ethyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethyl 4-biphenylmethy1 pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-1hiomethy lmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl “4-{N,N- dimethylamino) phenylme thyl" benzyl l-pyrolylmethyl l-pyrazolylmethyl 1-imida zolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4 -py r idylme thyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylmethyl l-pyrazolylmethyl 1-imidazolylmethyl l-indolylmethyl ·' l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyc1ohexylmethy1 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylmethyl 4—· 41“ methyl)piperidinyl- methyl "(3,4- methylenedioxyphenyl)m ethyl" 2-thienylmethy1 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thioroethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nit rophenylmethyl p-aminophenyl -inethyl "4-(N,N- dimethylamino)phenylme thyl" benzyl l-pyrolylmethyl l-pyrazolylmethyl 1-imidazolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolylroethyl 2- pyridylmethyl 3 -pyridy lmethyl 4-pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-nvethylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-®ethylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl 3-methylpentyl iaopropyl iaopropyl iaopropyl iaopropyl iaopropyl iaopropyl iaopcopyl iaopropyl iaopropyl isopxopyl iaopropyl iaoptopyl iaopropyl iaopropyl 141 LV 10096 3249 labie 5 4-(1- 2-thiophenylmethyl isopropyl 3250 methy 1) piperidinyl-methyl "(3/4- 4- (1- iaopropyl 3251 methylenedioxyphenyl) m ethyl" 2-thienylmethyl methyl)piperidinyl- methyl "(3,4- isopropyl 3252 4-biphenylmethyl methylenedioxyphenyl)m ethyl" 2-thienylroethyl * iaopropyl 3253 pyrimidinylmethyl 4-biphenylmethyl iaopropyl 3254 2-ben20thi&zolylmethyl pyriinidinylroethyl iaopropyl 3255 2- 2-benzothiazolylmethyl iaopropyl 3256 benzothiophenylmethyl 2-thiomethylethyl 2- iaopropyl 3257 2-thiomethylmethyl benzothiophenylmethyl 2-thioroethylethyl iaopropyl 3258 2-methylpropyl 2-thiomethylmethyl iaopropyl 3259 2-methylbutyl 2-methylpropyl iaopropyl 3260 3-methylbutyl 2-nvethylbutyl iaopropyl 3261 cyclopropylmethyl 3-methylbutyl iaopropyl 3262 cyclobutylmethyl cyclopropylmethyl iaopropyl 3263 cyclopentylmethyl cyclobutylmethyl iaopropyl 3264 p-hydroxyphenyl-methyl cyclopentylmethyl iaopropyl 3265 ρ-nit rophenylmethyl p-hydroxyphenyl-inethyl iaopropyl 3266 p-aminophenyl-methyl p-nitrophenylmethyl iaopropyl 3267 "4-(N,N- p-aminophenyl-methyl iaopropyl 3268 dimethylami.no)phenylme thyl" benzyl "4-(N,N- 3-methylbutyl 3269 l-pyrolylmethyl dimethylamino)phenylme thyl" benzyl 3-methylbutyl 3270 l-pyrazolylmethyl l-pyrolylmethyl 3-methylbutyl 3271 l-imidazolylmethyl 1-py r a z ο 1 y lroet hy 1 3-methylbutyl 3272 l-indolylmethyī l-imidazolylmethyl 3-methylbutyl 3273 l-triazolylmethyl l-indolylxrvethyl 3-methylbutyl 3274 1-tetrazolylmethy1 l-triazolylmethyl 3-methylbutyl 3275 2-pyridylmethyl l-tetrazolylmethyl 3-methylbutyl 3276 3-pyridylmethyl 2-pyridylmethyl 3-methylbutyl 3277 4-pyridylmethyl 3-pyridylmethyl 3-methylbutyl 3278 cyclohexylmethyl 4-pyridylmethyl 3-methylbutyl 3279 2-naphthylmethyl cyclohexylroethyl 3-roethylbutyl 3280 3-naphthylraethyl 2-naphthylmethyl 3-methylbutyl 3281 2-thiophenylmethyl 3-naphthylmethyl 3-methylbutyl 3282 4- (1- 2-thiophenylmethyl 3-®ethylbutyl 3283 methyl)piperidinyl- methyl "(3,4- 4- (1- 3-methylbutyl 3284 roethylenedioxyphenyl)m ethyl" 2-thienylmethyl methyl)piperidinyl- methyl "(3,4- 3-methylbutyl 3285 4-biphenylmethyl methylenedioxyphenyl)m ethyl" 2-thienylmethyl 3-methylbutyl 3286 pyrimidinylnvethyl 4-biphenylmethyl 3-methylbutyl 3287 2-benzothiazolylmethyl pyrimidinylmethyl 3-roethylbutyl 142 labis.5 3288 2- benzothiophenylmethyl . 2-benzothiazolyLmethyl 3-oethylbutyl 3289 2-thiomethylethyl 2- benzothiophenylroethyl 3-aethylbutyl 3290 2-thiomethylmethyl 2-thioaethylethyl 3-methylbutyl 3291 2-methylpropyl 2-thiomethylmethyl 3-aethylbutyl 3292 2-methylbutyl 2 -aethylpropyl 3-methylbutyl 3293 3-methylbutyl 2-methylbutyl 3-methylbutyl 3294 cyclopropylmethyl 3-methylbutyl 3-methylbutyl 3295 cyclobutylnethyl cyclopropylmethyl 3-methylbutyl 3296 cyclopentylmethyl cyclobutylmethyl 3-aethylbutyl 3297 p-hydroxyphenyl-methyl cyclopentylmethyl 3-aethylbutyl 3298 p-n it rophenylmethyl p-hydxoxyphenyl-inethyl 3-aethylbutyl 3299 p-aminophenyl-jnethyl p-nitrophenylinethyl 3-methylbutyl 3300 "4-(N,N- dimethylamino) phenylroe thyl" p-ajninophenyl-methyl 3-aethylbutyl 3301 benzyl *4-<N,N- dimethylamino) phenylme thyl" 2-phenylethyl 3302 l-pyrolylmethyl benzyl 2-phenylethyl 3303 l-pyrazolylmethyl l-pyrolyl»ethyl 2-phenylethyl 3304 l-imidazolyltnethyl l-pyrazolyl»ethyl 2-phenylethyl 3305 l-indolylsvethyl 1-imidazolylmethyl 2-phenylethyl 3306 l-triazolylmethyl l-indolylaethyl 2-phenylethyl 3307 l-tetrazolylmethyl 1-triazolylmethyl 2-phenylethyl 3308 2-pyridylmethyl l-tetrazolylaethyl 2-phenylethyl 3309 3-pyridylmethyl 2-pyridylmethyl 2-phenylethyl 3310 4-pyridybnethyl 3-pyridylmethyl 2-phenylethyl 3311 cyclohexylmethyl 4 -pyridyljnethyl 2-phenylethyl 3312 2-naphthylmethyl cyclohexylmethyl 2-phenylethyl 3313 3-naphthylmethyl 2-naphthylmethyl 2-phenylethyl 3314 2-thiophenylmethyl 3-naphthylroethyl 2-phenylethyl 3315 4-<l- methyl)piperidinyl- methyl 2-thiophenylmethyl 2-phenylethyl 3316 "(3,4- methylenedioxyphenyl)m ethyl" 4-(l- methyl)piperidinyl-methyl 2-phenylethyl 3317 2-thienylmethyl "(3/4- methylenedioxyphenyl)a ethyl" 2-phenylethyl 3318 4-biphenylmethyl 2-thienylmethyl 2-phenylethyl 3319 pyrimidinylmethyl 4-biphenylmethyl 2-phenylethyl 3320 2-benzothiazolylmethyl pyrimidinylinethyl 2-phenylethyl 3321 2- benzothiophenylmethyl 2-ben z oth i a z olylaethy1 2-phenylethyl 3322 2-thiomethylethyl 2- benzothiophenylmethyl 2-phenylethyl 3323 2-th iome thylme thyl 2-thiomethylethyl 2-phenylethyl 3324 2-methylpropyl 2-thiomethylmethyl 2-phenylethyl 3325 2-methylbutyl 2-methylpropyl 2-phenylethyl 3326 3-methylbutyl 2-methylbutyl 2-phenylethyl 3327 cyclopropylmethyl 3-methylbutyl 2-phenylethyl 3328 cyclobutylmethyl cyclopropylaethyl 2-phenylethyl 3329 cyclopentylmethyl cyclobutylmethyl 2-phenylethyl 3330 p-hydroxypheny 1 -methyl cyclopentylinethyl 2-phenylethyl

143labie S p-nitrophenylmethyl p-aminophenyl-methyl •4-(N,N- dimethylami.no)phenylme thyl* benzyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl LV 10096 2-phenylethyl 2-phenylethyl 2-phenylethyl 1 -pyrolylmethyl l-pyrazolylmethyl l-imidazolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylinethyl 2-thiophenylmethyl 4- (l- methyl)piperidinyl- methyl •(3,4- methylenedioxyphenyl)m ethyl" 2-thienylraethyl "4-(N,K- dimethylamino)phenylme thyl" benzyl l-pyrolylmethyl 1-pyrazolylmethy1 l-imidazolylmethyl l-indolylmethyl l-triazolylmethyl 1- tetrazolylmethyl 2- pyridylmethyl 3- pyridylmethyl 4- pyridylmethyl cyclohexylmethyl 2- naphthylmethyl 3- naphthylmethyl 2-thiophenylmethyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 4-biphenylmethyl pyrimidinylmethyl 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl "4-(N,N- dimethylami no) phenylroe thyl· benzyl 4- (1- methyl)piperidinyl- methyl "(3,4- methylenedioxyphenyl)o ethyl" 2-thienylmethyl 4-biphenylroethyl pyrimi dinylmethy1 2-benzothiazolylmethyl 2- benzothiophenylmethyl 2-thiomethylethyl 2-thiomethylmethyl 2-methylpropyl 2- methylbutyl 3- methylbutyl cyclopropylmethyl cyclobutylmethyl cyclopentylmethyl p-hydroxyphenyl-methyl p-nitrophenylmethyl p-aminophenyl-methyl 3-phenylpropyl 3-pbenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpr opy1 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-phenylpropyl 3-pbenylpropyl 1-pyrolylmethyl •4-(N,N- dimethylamino) phenylme thyl- benzyl "2-(W,N- diroethylamino) ethyl" •2-(M,N- dimethylamino) ethyl" 144

Iable..,.S l-pyrazolylmethyl l-pyrolylmethyl "2- (N,N- dimethylamino) ethyl" l-imidazolylmethyl l-pyrazolylmethyl "2- (N,N- dimethylamino) ethyl" l-indolylmethyl l-imidazolylmethyl "2-(N,N- dimethylamino) ethyl" l-triazolylmethyl 1-indolylmethyl "2-(K,H- dimethylamino) ethyl" l-tetrazolylmethyl * l-triazolylmethyl "2-(N,N- dimethylamino) ethyl" 2-pyridylmethyl 1-tet ra zolylmethyl "2-(N,N- dimethylamino) ethyl" 3 -py r idy lmethy 1 2-pyridylmethyl "2- (N,N- dimethylaiiu.no) ethyl" 4-pyridylmethyl 3-pyridylmethyl "2-(N, N- dimethylamino) ethyl" cyclohexylmethyl 4-pyridylmethyl "2-(N,N- dimethylamino) ethyl·* 2-naphthylmethyl cyclohexylmethyl "2-(N,N- dimethylami.no) ethyl" 3-naphthylmethyl 2-naphthylmethyl "2-(N,N- dimethylamino) ethyl" 2-thiophenylmethyl 3-naphthylmethyl •2-(N,N- dimethylamino) ethyl" 4- (1- methyl)piperidinyl-methyl 2-thiophenylmethyl "2-(N,N- dimethylamino) ethyl" *(3,4- 4 — {1— "2-(N,N- methylenedioxyphenyl)m methyl)piperidinyl- dimethylamino) ethyl" methyl ethyl" 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" "2-(N,K- dimethylamino) ethyl" 4-biphenylmethyl 2-thienylmethyl "2- (N,N- dimethylamino) ethyl" pyrimidinylmethyl 4-biphenylmethyl "2-(N, N- dimethylamino) ethyl" 2-benzothiazolylmethyl pyr imidiny lmethy 1 "2-(N,N-dimethylamino) ethyl" 2- benzothiophenylmethyl 2-benzothiazolylmethyl "2-(N,N- dimethylamino) ethyl" 145 LV 10096 labie 5 2-thiomethylethyl 2- •2-(N,N- 2-thiomethylmethyl benzothiophenylmethyl 2-thiomethylethyl dimethylami.no) ethyl" "2-(N,N- 2-methylpropyl 2-thiomethylmethyl dimethylamino) etl^l" "2-(N,N- 2-methylbutyl 2-methylpropyl dimethylamino) ethyl" "2-(N,N- 3-methylbutyl 2-methylbutyl dimethylamino) ethyl" •2-<N,N- cyclopropylmethyl 3-methylbutyl dimethylamino) ethyl" "2-(N,N- cyclobutylmethyl cyclopropylmethyl diroethylamino) ethyl" 2-(N,N- cyclopentylmethyl cyclobutylmethyl dimethylamino) ethyl" "2-(N,N- p~hydroxyphenyl-methyl cyclopentylmethyl dimethylamino) ethyl" "2-(N/N- p-nitrophenylmethyl p-hydroxyphenyl-methyl dimethylamino) ethyl" •2-(N,N- p-aminophenyl-methyl p-nitrophenylmethyl dimethylamino) ethyl" "2-(N,N- "4-(N,N- p-aminophenyl-methyl dimethylamino) ethyl" "2-(N,N- dimethylamino) phenylme thyl" benzyl *4-(N,N- dimēthylamino) ethyl" 3- l-pyrolylmethyl dimethylamino)phenylme thyl" benzyl oxetanylmethyl 3- l-pyrazolylmethyl l-pyrolylmethyl oxetanylmethyl 3- l-imidazolylmethyl l-pyrazolylmethyl oxetanylmethyl 3- l-indolylmethyl l-imidazolylmethyl oxetanylmethyl 3- l-triazolylmethyl 1-indolylmethy1 oxetanylmethyl 3- 1-tet ra zolylmethyl 1-triazolylmethy1 oxetanylmethyl 3- « 2-pyridylxnethyl 1-tet ra zolylmethyl oxetanylmethyl 3- 3-pyridylinethyl 2-py r idy lmethy 1 oxet anylmethyl 3- 4-pyridylmethyl 3-pyridylroethyl oxetanylmethyl 3- oxetanylmethyl 146

Table 5 cyclohexylmethyl 4-pyridylmethyl 3- 2-naphthylmethyl cyclohexylmethyl oxetanylmethyl 3- 3-naphthyLnethyl 2-naphthylmethyl oxetanylmethyl 3- 2-thiophenyLnethyl 3-naphthy Lnethy1 oxetanyLnethyl 3- 4—{1— 2-thiophenyLnethyl oxetanyLnethyl 3- methyl)piperidiny1-methyl oxetanylmethyl "(3,4- 4- (1- 3- methylenedioxyphenyl)m methyl)piperidinyl- oxetanylmethyl ethyl" 2«thieny Lnethy1 inethyl "(3,4- 3- 4-biphenylmethyl methylenedioxyphenyl)m ethyl'' 2-thienylroethyl oxet anylmethyl 3- pyrimldinylmethyl 4-biphenylmethyl oxetanylaethyl 3- 2-benzothiazolylmethyl pyrimidinylnvethyl oxetanylnethyl 3- 2- 2-benzothiazolylntethyl oxetanyLnethyl 3- benzothiophenylmethyl 2-thiomethylethyl 2- oxetanyLaethyl 3- 2-thioinethyLnethyl benzothiophenylmethyl 2-thiomethylethyl oxetanylmethyl 3- 2-methylpropyl 2-thiomethylmethyl oxetanylmethyl 3- 2-methylbutyl 2-methylpropyl oxetanylmethyl 3- 3-methylbutyl 2-methylbutyl oxetanylroethyl 3- cy c 1 opr opy Lite thy 1 3-methylbutyl oxetanylmethyl 3- cyclobutylmethyl cyclopropylinethyl oxetanybnethyl 3- cyclopentylmethyl cyclobutylmethyl oxetanylmethyl 3- p-hydroxyphenyl-methyl cyclopentylmethyl oxetanylmethyl 3- p-nitrophenylmethyl p-hydroxyphenyl-methyl oxetanylmethyl 3- p-aminophenyl-methyl p-nit rophenylmethyl oxet anylmethy1 3- •4-(N,K- p-aminophenyl-methyl oxetanylmethyl 3- dLnethylamlno) phenylme thyl- benzyl "4-(N,N- oxetanylmethyl 2- l-pyrolylmethyl dimethylamino)phenylroe thyl" benzyl tetrahydrofura nyl 2- tetrahydrofura nyl 147 LV 10096 l-pyrazolyl®ethyl l-pyrolylxnethyl 2- tetrahydrofura nyl l-imidazolyljnethyl l-pyrazolylmethyl 2- tetrahydrofura nyl 1-indolylmethyl 1-imidazoly lmethy1 2- tetrahydrofura nyl l-triazolylmethyl l-indolylroethyl 2- tetrahydrofura nyl l-tetrazolylmethyl l-triazolylmethyl 2- tetrahydrofura nyl 2-pyridylmethyl l-tetrazolylmethyl 2- tetrahydrofura nyl 3-pyridylmethyl 2-pyridylroethyl 2- tetrahydrofura nyl 4-pyridylmethyl 3 -py r idy linethy 1 2- tetrahydrofura nyl cyclohexylmethyl 4-pyridylmethy1 2- tetrahydrofura nyl 2-naphthylmethyl cyclohexylmethyl 2- tetrahydrofura nyl 3-naphthylmethyl 2-naphthy lmethyl 2- tetrahydrofura nyl 2-thiophenylmethyl 3-naphthylmethyl 2- tetrahydrofura nyl 4-(l- methyl)piperidinyl-methyl 2-thiophenylroethyl 2- tetrahydrofura nyl (3,4* 4-(1- 2- methylenedioxyphenyl> m methyl)pipetldinyl- tetrahydrofura ethyl" wethyl nyl 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" 2- tetrahydrofura nyl 4-biphenylmethyl 2-thienylmethyl 2- tetrahydrofura nyl pyrimidinylmethyl 4-biphenylroethy1 2- tetrahydzofura nyl 2-benzothiazolylmethyl pyrimidinylnvethyl 2- tetrahydro£ura nyl 2- benzothlophenylmethyl 2-benzothlazolylmethyl 2- tetrahydrofura nyl 148labie .5 3454 2-thiomethylethyl 2- benzothiophenylmethyl 2- tetrahydrofura nyl 3455 2-thiomethylmethyl 2-thiomethylethyl 2- tetrahydrofura nyl 3456 2-methylpropyl 2-thioroethylmethyl 2- tetrahydrofura nyl 3457 2-methylbutyl 2-methylpropyl 2- tetrahydrofura nyl 3458 3-methylbutyl 2-methylbutyl 2- tetrahydrofura nyl 3459 cyclopropylmethyl 3-methylbutyl 2- tetrahydrofura nyl 3460 cyclobutylmethyl cyclopropylmethyl 2- tetrahydrofura nyl 3461 cyclopentylmethyl cyclobutylmethyl 2- tetrahydrofura nyl 3462 p-hydroxyphenyl-methyl cyclopentylmethyl 2- tetrahydrofura nyl 3463 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2~ tetrahydrofura nyl 3464 p-aminophenyl-methyl p-nitrophenylmethyl 2- tetrahydrofura nyl 3465 "4-(N,N- dimethylamino)phenylme thyl" p-aminophenyl-inethyl 2- tetrahydrofura nyl 3466 benzyl "4-(N/N- dimethylami.no)phenylme thyl" 2- methoxypropyl 3467 l-pyrolylmethyl benzyl 2- methoxypropyl 3468 l-pyrazolylmethyl l-pyrolylmethyl 2- methoxypropyl 3469 l-imidazolylmethyl l-pyrazolylmethyl 2- methoxypropyl 3470 l-indolylmethyl 1-imidazolylmethyl 2- methoxypropyl 3471 l-triazolylmethyl l-indolylmethyl 2- methoxyp ropy1 3472 1-tet ra zolylmethyl l-triazolylmethyl 2- methoxypropyl 3473 2-pyr idylmethyl l-tetrazolylmethyl 2- methoxypropyl 3474 3-pyridylmethyl 2-pyridylmethyl 2- meth«xypropyl 3475 4-pyridylmethyl 3-pyridylmethyl 2- methoxypropyl 149 LV 10096 labie 5 cyclohexylnethyl 4-pyridylmethyl 2- methoxypropyl 2-naphthyljnethyl cyclohexylmethyl 2- methoxypropyl 3-naphthylnvethyl 2-naphthylmethyl 2- methoxypropyl 2-thiophenylmethyl 3-naphthylmethyl 2- methoxypropyl 4- (1- methyl) piperidinyl-methyl 2-thiophenylmethyl f 2- methoxypropyl "(3,4- 4-<l- 2- nvethylenedioxyphenyl) m ethyl" methyl)piperidinyl-methyl methoxypropyl 2-thienylmethyl "(3,4- methylenedioxyphenyl)n ethyl“ 2- methoxypropyl 47biphenylmethyl 2-thienylmethyl 2- methoxypropyl pyrimidinylmethyl 4-biphenylmethyl 2- methoxypropyl 2-benzothiazolylmethyl pyriiTLidinylmethyl 2- methoxypropyl 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2- methoxypropyl 2-thiomethylethyl 2- benzothiophenylmethyl 2- methoxypropyl 2-thiomethylmethyl 2-thiomethylethyl 2- methoxypropyl 2-methylpropyl 2-thiomethylmethyl 2- methoxypropyl 2-methylbutyl 2-methylpropyl 2- methoxyptopyl 3-methylbutyl 2-methylbutyl 2- n>ethoxypropyl cyc1opropylme t hy1 3-methylbutyl 2- methoxypropyl cyclobutylmethyl cyclopropylmethyl 2- roethoxypropyl cyclopentylmethyl cyclobutylmethyl 2- methoxypropyl p-hydroxyphenyl-methyl cyclopentylroethyl 2- methoxypropyl p-nitrophenylmethyl p-hydroxyphenyl-methyl 2- methoxypropyl p-aminophenyl-it>ethyl p-nit rophenylmethyl 2- roethoxypropyl "4-(Η, N- di®ethylamino) phenylme p-arainophenyl-methyl 2- methoxypropyl thyl" 4 benzyl "4- (N,H- dimethylamino) phenyline thyl" 2-ethoxyethyl l-pyrolylinethyl benzyl 2-ethoxyethyl l-pyrazolylmethyl l-pyrolylmethyl 2-ethoxyethyl l-imidazolylmethyl l-pyrazolylmethyl 2-ethoxyethyl l-indolylmethyl 1-imidazolylmethyļ 2-ethoxyethyl 150 labie 5 3504 l-triazolyl»ethyl l-indolylmethyl 2-ethoxyethyl 3505 l-tetrazolybnethyl l-triazolylmethyl 2-ethoxyethyl 3506 2-pyridylmethyl l-tetrazolylmethyl 2-ethoxyethyl 3507 3 -py r idy lroethyl 2-pyridylmethyl 2-ethoxyethyl 3506 4-pyridylmethyl 3-pyridylmethyl 2-ethoxyethyl 3509 cyclohexylmethyl 4-pyridylmethyl 2-ethoxyethyl 3510 2-naphthylmethyl cyclohexyl»ethyl 2-ethoxyethyl 3511 3-naphthylnethyl 2-naphthylmethyl 2-ethoxyethyl 3512 2-thiophenylmethyl 3-naphthylmethy1 2-ethoxyethyl 3513 4-U- nethy 1) pipe r idinyl-methyl 2-thiophenylmethyl 2-ethoxyethyl 3514 "(3,4- methylenedioxyphenyl) ro ethyl'* 4- (1- methyl)piperidinyl-methyl 2-ethoxyethyl 3515 2-thienyl»ethyl "(3,4- methylenedioxyphenyl)m ethyl" 2-ethoxyethyl 3516 4-biphenylmethyl 2-thlenylinethyl 2-ethoxyethyl 3517 pyriīnidinylnethyl 4-biphenylmethyl 2-ethoxyethyl 3518 2-benzothiazolylroethyl pyrinddinylmethyl 2-ethoxyethyl 3519 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2-ethoxyethyl 3520 2-thiomethylethyl 2- benzothiophenylmethyl 2-ethoxyethyl 3521 2-thiomethyln>ethyl 2-thiomethylethyl 2-ethoxyethyl 3522 2-methylpropyl 2-thiomethylmethyl 2-ethoxyethyl 3523 2-methylbutyl 2-methylpropyl 2-ethoxyethyl 3524 3-methylbutyl 2-methylbutyl 2-ethoxyethyl 3525 cyclopropylmethyl 3-n>ethylbutyl 2-ethoxyethyl 3526 cyclobutylmethyl cyclopropylmethyl 2-ethoxyethyl 3527 cyclopentylmethyl cyclobutylioethyl 2-ethoxyethyl 3528 p-hydroxyphenyl-roethyl cyclopentylmethyl 2-ethoxyethyl 3529 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2-ethoxyethyl 3530 p-aminophenyl-methyl p-nitrophenylmethyl 2-ethoxyethyl 3531 "4-(N,N- dimethylamino)phenylme thyl" p-aminophenyl-methyl 2-ethoxyethyl 3532 benzyl "4-(N,N- dimethylamino)phenylne thyl" 2-{1- pyrolyl) ethyl 3533 l-pyrolylmethyl benzyl 2-{l- pyrolyl)ethyl 3534 l-pyrazolylmethyl l-pyrolylmethyl 2-U- pyrolyl)ethyl 3535 l-imidazolyljnethyl l-pyrazolylmethyl 2-(l- pyrolyl)ethyl 3536 l-indolylmethyl l-imidazolylmethyl 2-U- pyrolyl)ethyl 3537 l-triazolylmethyl l-indolylmethyl 2-U- pyrolyl)ethyl 3538 l-tetrazolylmethyl l-triazolylmethyl 2-(l- pyrolyl)ethyl 3539 2-pyridylmethyl l-tetrazolylmethyl 2-{l- pyrolyl)ethyl 3540 3-pyridylinethyl 2-pyridylmethyl 2-U- · pyrolyl)ethyl 151 151 TablP 5 3541 4-pyridylmethyl 3-pyridylmethyl 3542 cyclohexylmethyl 4-pyridylmethyl 3543 2-naphthylmethyl cyclohexylmethyl 3544 3-naphthylmethyl 2-naphthylmethyl 3545 2-thiophenylmethyl 3-naphthylmethyl 3546 4-(l- methyl)pipe ridinyl-methyl 2-thiophenylmethyl 3547 "(3,4- methylenedioxyphenyl)o ethyl" 4-(l- inethyl) piperidinyl-methyl 3548 2-thienylmethyl " <3,4- methylenedioxyphenyl)m ethyl" 3549 4-biphenylroethyl 2-thienylmethyl 3550 pyrimidinylmethyl 4-bipheny lmethy1 3551 2-benzothiazolylmethyl pyrimidinylmethyl 3552 2- benzothiophenylmethyl 2-benzothiazolylmethyl 3553 2-thiomethylethyl 2- benzothiophenylmethyl 3554 2-thiomethylmethyl 2-thiomethylethyl 3555 2-methylpropyl 2-thiomethylmethyl 3556 2-methylbutyl 2-methylpropyl 3557 3-methylbutyl 2-methylbutyl 3558 cyclopropylmethyl 3-methylbutyl 3559 cyclobutylmethyl cyclopropylmethyl 3560 cyclopentylmethyl cyclobutylmethyl 3561 p-hydroxyphenyl-methyl cyclopentylmethyl 3562 p-nitrophenylmethyl p-hydroxyphenyl-methyl 3563 p-aminophenyl-methyl p-nitrophenylmethyl 3564 "4-(N,H- diroethylamino) phenylne thyl" p-aminophenyl-methyl 3565 benzyl "4-(N,N- dimethylamino)phenylme thyl" LV 10096 2-(l- pyrolyl)ethyl 2— {1— pyrolyl)ethyl 2 - (1— pyrolyl)ethyl 2 - (1— pyrolyl)ethyl 2 - {1 - pyrolyl)ethyl 2-(1- pyrolyl)ethyl 2-(1- pyrolyl)ethyl 2- (1- pyrolyl)ethyl 2- (1- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-(l- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-(l- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-(l- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-(l- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyl 2-U- pyrolyl)ethyli 2-(l- imidazolyl)eth yi 152

Table 5 l-pyrolylmethyl benzyl 2-<l- l-pyrazolylmethyl l-pyrolylmethyl imidazolyl)eth yi 2-U- l-imidazolylmethyl l-pyrazolylmethyl imidazolyl)eth yi 2-u- l-indolylmethyl l-imidazolylmethyl imidazolyl)eth yi 2-U- l-triazolylmethyl , l-indolylroethyl imidazolyl)eth yi 2-U- l-tetrazolylmethyl l-triazolylmethyl imidazolyl)eth yi 2-U- 2-pyridylmethyl l-tetrazolylinethyl imidazolyl)eth yi 2-u- 3-pyridylmethyl 2-pyridylmethyl imidazolyl)eth yi 2-U- 4-pyridylmethyl 3-pyridylmethyl imidazolyl)eth yi 2-U- cyclohexylmethyl 4-pyridylroethyl lmidazolyl)eth yi 2-U- 2-naphthylmethyl cyclohexylmethyl imldazolyl)eth yi 2-U- 3-naphthylmethyl 2-naphthylmethyl imidazolyl)eth yi 2-U- 2-thiophenylinethyl 3-naphthylmethy1 imidazolyl) eth yi 2-U- 4-(1- 2-thiophenylmethy1 imidazolyl)eth yi 2-U- methyl)piperidinyl- inethyl "(3,4- 4-{l- imidazolyl)eth yi 2-u- methylenedioxyphenyl)m methyl)piperidinyl- imidazolyl)eth ethyl* methyl yi 2-thienylmethyl "(3,4- 2-u- 4-biphenylmethyl methylenedioxyphenyl)m ethyl" 2-thienylmethyl imidazolyl)eth yi 2-u- pyrimidinylmethyl 4-biphenylmethyl imidazolyl)eth yl 2-(l- 2-benzothiazolylmethyl pyrimidinylmethyl imidazolyl)eth yi 2-u- imidazolyl)eth yi 153 LV 10096

Iablg-5 3585 2- benzothiophenylmethyl 2-benzothiazolylmethyl 2— (1— imidazolyl)eth yi 3586 2-thiomethylethyl 2- benzothiophenylmethyl 2-(1- imidazolyl)eth yi 3587 2-thiomethylmethyl 2-thiomethylethyl 2- (1- imidazolyl)eth yi 3588 2-methylpropyl 2-thiomethylmethyl 2 - (1 - imidazolyl)eth yi 3589 2-methylbutyl 2-methylpropyl 2-(1- imidazolyl)eth yi 3590 3-methylbutyl 2-methylbutyl 2 - (1— imidazolyl)eth yi 3591 cyclopropylffiethyl 3-methylbutyl 2-(l- imidazolyl)eth yi 3592 cyclobutylmethyl cyclopropylmethyl 2 - (1 - imidazolyl)eth yi 3593 cyclopentylmethy1 cyclobutylmethyl 2-(l- imidazolyl)eth yi 3594 p-hydroxyphenyl-methyl cyclopentylmethyl 2 — (1— imidazolyl)eth yi 3595 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2 - (1— lmldazolyl)eth yi 3596 p-aminophenyl-methyl p-nit rophenylmethy1 2-(l- imidazolyl)eth yi 3597 "4-(N,N- dimethylamino) phenyline thyl" p-aminophenyl-methyl 2 - (1— imidazolyl)eth yi 3598 benzyl M-(N,N- dimethylamino) phenylme thyl* 2- pyridylmethyl 3599 1-pyrolylmethyl benzyl 2- pyridylmethyl 3600 1 -py ra zo ly lroet hy 1 l-pyrolylmethyl 2- pyridylmethyl 3601 l-imidazolyl»ethyl l-pyrazolylmethyl 2- pyridylmethyl 3602 l-indolylmethyl l-imidazolylmethyl 2- pyridylmethyl ‘ 3603 l-triazolylmethyl l-indolylmethyl 2- pyridylmethyl 3604 l-tetrazolylmethyl l-triazolylmethyl 2- pyridylmethyl 3605 2-pyridylmethyl l-tetrazolylmethyl . 2- pyridylmethyl 154 labie 5 3606 3-pyridylmethyl 2-pyridylmethyl 2- pyridylmethyl 3607 4-pyridylmethyl 3-pyridylmethyl 2- pyridylmethyl 3608 cyclohexylmethyl 4-pyridylmethyl 2- pyridylmethyl 3609 2-naphthylmethy1 cyclohexylmethyl 2- pyridylmethyl 3610 3-naphthylroethyl 2-naphthylmethyl 2- pyridylmethyl 3611 2-thiophenylmethyl 3-naphthylmethyl 2- pyridylmethyl 3612 4-<l- methyl)piperidinyl-methyl 2-thiophenylmethyl 2- pyridylmethyl 3613 "(3,4- 4-(l- 2- methylenedloxyphenyl)m ethyl" methyl)pipe ridinyl-roethyl pyridylmethyl 3614 2-thienylmethyl "(3,4- methylenedioxyphenyl)m ethyl" 2- pyridylmethyl 3615 4-biphenylmethyl 2-thienylmethyl 2- pyridylmethyl 3616 pyrimidinylmethyl 4-biphenylmethyl 2- pyridylmethyl 3617 2-benzothiazolylmethyl pyrimidinylmethyl 2- pyridylmethyl 3618 2- benzothlophenylmethyl 2-benzothiazolylmethyl 2- pyridylmethyl 3619 2-thiomethylethyl 2- benzothiophenylmethyl 2- pyridyl»ethyl 3620 2-thiomethylmethyl 2-thiomethylethyl 2- pyridylmethyl 3621 2-methylpropyl 2-thiomethylroethyl 2- pyridylmethyl 3622 2-methylbutyl 2-roethylpropyl 2- pyridylmethyl 3623 3-roethylbutyl 2-methylbutyl 2- pyridylmethyl 3624 c"yclopropylmethyl 3-methylbutyl 2- pyridylmethyl 3625 cyclobutylmethyl cyclopropylmethyl 2- pyridylmethyl 3626 cyclopentylmethyl ’cyclobutylmethyl 2- pyridylmethyl 3627 p-hydroxyphenyl-methyl cyclopentylmethyl 2- pyridylmethyl 3628 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2- pyridylmethyl 3629 p-aminophenyl-methyl p-nitrophenylmethyl 2- pyridylmethyr 3630 "4-(M,N- dimethylami.no) phenylme thyl· p-amlnophenyl-methyl 2- pyridylmethyl 3631 benzyl "4-(N,N- dimethylamino)phenylme 2- thiomethylethy thyl" 1 155lablč $ LV 10096 3632 l-pyrolylmethyl benzyl 2- thiomethylethy 1 3633 l-pyrazolylmethyl l-pyrolylmethyl A 2- thiomethylethy 1 3634 l-imidazolylmethyl l-pyrazolylmethyl A 2- thiomethylethy 1 3635 l-indolylroethyl l-imidazolylmethyl A 2- thiomethylethy 1 3636 l-triazolylraethyl l-indolylmethyl A 2- thiomethylethy 1 3637 l-tetrazolylmethyl l-triazolylmethyl A 2- thiomethylethy 1 3638 2-pyridyltnethyl l-tetrazolylroethyl A 2- thiomethylethy 1 3639 3-pyridylmethyl 2-pyridylmethyl 2- thiomethylethy l 3640 4-pyridylmethyl 3-pyridylmethyl A 2- thiomethylethy 1 3641 cyclohexylmethyl 4-pyridylmethy1 2- thiomethylethy 1 3642 2-naphthylmethyl cyclohexylmethyl A 2- thioraethylethy 1 3643 3-naphthylmethyl 2-naphthylmethyl 2- thiomethylethy 1 3644 . 2-thiophenylmethyl 3-naphthylmethyl 2- thiomethylethy 7 3645 4-tiniet hyl) piperidinyl-methyl 2-thiophenylroethyl A 2- thiomethylethy 1 3646 "(3,4- roethylenedioxyphenyl)m ethyl" 4-{l- methyl)piperidinyl-methyl 2- thiomethylethy 1 3647 2-thienylmethyl "{3,4- methylenedioxyphenyl) m ethyl" 2- thiomethylethy 1 3648 4-biphenylmethyl 2-thienylmethyl 2- thiomethylethy 1 v 3649 pyrimidinylmethyl 4-biphenylmethyl A 2- thiomethylethy 1 3650 2-benzothiazolylroethyl pyrimidinylmethyl A 2- thioroethylethy 1 156labie.5 3651 2- benzothiophenylnvethyl 2-benzothiazolylmethyl 2- thiomethylethy 1 3652 2-thiomethylethyl 2- benzothiophenylmethyl 2- thiomethylethy 1 3653 2-thiomethylmethyl 2-thiomethylethyl 2- thiomethylethy 1 3654 2-inethylpropyl 2-thiomethylmethyl 2- thiomethylethy 1 3655 2-methylbutyl 2-methylpropyl Λ 2- thiomethylethy 1 3656 3-n>ethylbutyl 2-methylbutyl 2- thiomethylethy 1 3657 cyc lopropylmethyl 3-methylbutyl J» 2- thiomethylethy 1 3658 cyclobutylmethyl cyclopropylmethyl 2- thiomethylethy 1 3659 cyclopentyljnethyl cyclobutylmethyl Λ 2- thiomethylethy 1 3660 p-hydroxyphenyl-methyl cyclopentylmethyl 2- thiomethylethy 1 3661 p-nitrophenylmethyl p-hydroxyphenyl-methyl 2- thiomethylethy 1 3662 p-aminophenyl-methyl p-nit rophenylmethyl 2- thiomethylethy 1 3663 3664 "4-(N,N- dimethylami.no) phenylme thyl" p-aminophenyl-methyl *4-(Nf'N· dimethylamino)phenylme thyl" 2- thiomethylethy 1 157LV 10096

Table 6 TABLE 6

Es.ainslfl Numbftg Ε4 EJ R22 3665 benzyl "4-(N,N-di- methyl-ami.no)-phenylmethyl" allyl 3666 1- pyrolylmethyl benzyl allyl 3667 1- pyrazolylmethy l-pyrolylmethyl allyl 3668 1- imida zolylmeth yi i- pyrazolylmethyl allyl 3669 1- indolylmethyl 1- imidazolylmethyl allyl 3670 1- triazolylmethy 1 l-indolylmethyl allyl 3671 1- tetrazolylmeth yi 1- triazolylmethyl allyl 3672 2- pyridylmethyl 1- tetrazolylmethyl allyl 3673 3- pyridylmethyl 2-pyridylmethyl allyl 3674 4- pyridylmethyl 3-pyridylmethyl allyl 3675 cyclohexylroeth yi 4-pyridylmethyl allyl R23 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thiomethylethyl 2- thioroethylethyl 2- thioroethylethyl 159

Table 6 3697 *4-(N/N-dimethylam-ino)phenyljneth yl" p-aminophenyl- methyl allyl 2- thiomethylethyl 3698 benzyl "4-{N,N- dimethylami.no)ph enylmethyl" propyl allyl 3699 1- pyrolylroethyl benzyl propyl allyl 3700 1- pyrazolylmethy l l-pyrolylmethyl propyl allyl 3701 Λ 1- imidazolylmeth yi 1- · pyrazolylmethyl propyl allyl 3702 1- indolylmethyl 1- imidazolylmethyl propyl allyl 3703 1- triazolyl»ethy 1 l-indolylmethyl propyl allyl 3704 J. 1- tetrazolylmeth yi 1- triazolylmethyl propyl allyl 3705 2- pyridylmethyl 1- tetrazolylmethyl propyl allyl 3706 3- pyridylroethyl 2-pyridylmethyl propyl allyl 3707 4- pyridylmethyl 3-pyridylmethyl propyl allyl 3708 cyclohexylmeth yi 4-pyridylmethyl propyl allyl 3709 2- naphthylmethyl cyclohexylmethyl propyl allyl 3710 3- naphthylmethyl 2-naphthylmethyl propyl allyl 3711 2- * thiophenylmeth yi 3-naphthylmethy1 propyl allyl 3712 4-(l- methyl)piperid inyl-methyl 2- thiophenylmethyl propyl allyl 3713 " (3» 4- methylenedioxy phenyl)jnethyl" 4-(1- methyl)piperidin yl-methyl propyl allyl 3714 2- thienylmethyl - (3,4- methylenedioxyph enyl)methyl" propyl allyl 3715 4- biphenylmethyl 2-thienylmethyl propyl allyl 3716 pyrimidinylmet hyl 4-biphenylmethyl propyl allyl C 3717 2- benzothiazolyl methyl pyrimidinylmethy 1 propyl allyl 3718 2- benzothiopheny lmethyl 2- benzothiazolylme thyl propyl allyl 160 Table 6 LV 10096 3719 2- thiomethylethy X 2- benzothiophenylm ethyl propyl allyl 3720 2- thiomethylmeth yi 2- thiomethylethyl propyl allyl 3721 2-methylpropyl 2- thiomethylmethyl propyl allyl 3722 2-methylbutyl 2-methylpropyl propyl allyl 3723 3-methylbutyl 2-methylbutyl propyl allyl 3724 cyclopropylnvet hyl 3-methylbutyl propyl allyl 3725 cyclobutylineth yi cyclopropylmethy 1 propyl allyl 3726 cyclopentylmet hyl cyclobutylmethyl propyl allyl 3727 p- hydroxyphenyl- methyl cyclopentylmethy 1 propyl allyl 3728 p- nitrophenylmet hyl p-hydroxyphenyl- methyl propyl allyl 3729 p-aminophenyl- n»ethyl p- nitrophenylmethy 1 propyl allyl 3730 *4-(N,N- diitiethylamino) phenylmethyl" t X p-aminophenyl- methyl propyl allyl 3731 benzyl "4-(N,N- dimethylami.no)ph enylmethyl" n-butyl propyl 3732 1- pyrolylmethyl benzyl n-butyl propyl 3733 1- pyrazolylmethy l l-pyrolylmethyl n-butyl propyl 3734 X 1- imidazolylmeth yi 1" pyrazolylmethyl n-butyl propyl 3735 1- indolylmethyl 1- imida zolylmethyl n-butyl propyl 3736 1- triazolylmethy 1 l-indolylmethyl n-butyl propyl 3737 X 1-. tetrazolylmeth yi 1- triazolylmethyl n-butyl propyl 3738 2- pyridylmethyl 1- tetrazolylmethyl n-butyl propyl 3739 3- pyridylmethyl 2-pyridylmethyl n-butyl propyl 3740 4- pyridylmethyl 3-pyridylmethyl n-butyl propyl 3741 cyclohexylmeth yi 2- naphthylmethyl 4-pyridylmethyl n-butyl propyl 3742 cyclohexylmethyl n-butyl propyl 161

Table 6 3743 3- naphthylmethyl 2-naphthylmethyl n-butyl propyl 3744 2- thiophenylmeth yi 3-naphthylmethyl n-butyl propyl 3745 4-(l- methyl)piperid inyl-methyl 2- thiophenylmethyl n-butyl propyl 3746 "(3,4- roethylenedioxy phenyl)ioethyl" 4 — (1— methyl)piperidin yl-methyl n-butyl propyl 3747 2- thienylmethyl "(3,4- nethylenedioxyph enyl)methyl" n-butyl propyl 3748 4- biphenylmethyl 2-thienylmethyl n-butyl propyl 3749 pyrimidinylmet hyl 4-biphenylmethyl n-butyl propyl 3750 2- benzothiazolyl methyl pyrimidinylmethy 1 n-butyl propyl 3751 2- benzothiopheny lmethyl 2- benzothiazolylme thyl n-butyl propyl 3752 2- thiomethylethy 1 2- benzothiophenyljn ethyl n-butyl propyl 3753 2- thiomethylmeth yi 2- thiomethylethyl n-butyl propyl 3754 2-methylpropyl 2- thiomethylmethyl n-butyl propyl 3755 2-methylbutyl 2-methylpropyl n-butyl propyl 3756 3-methylbutyl 2-methylbutyl n-butyl propyl 3757 cyclopropyljnet hyl 3-methylbutyl n-butyl propyl 3758 cyclobutylmeth yi cyclopropyimethy 1 n-butyl propyl 3759 cyclopentyljnet hyl cyclobutylmethyl n-butyl propyl 3760 p- hydroxyphenyl- methyl p- nitrophenylmet hyl cyclopentylmethy 1 n-butyl propyl 3761 p-hydroxyphenyl- methyl n-butyl propyl 3762 p-aminophenyl- methyl p- nit rophenylmethy 1 n-butyl propyl 3763 "4-(N,N- dimethylamino) phenylmethyl" X p-aminophenyl- methyl n-butyl propyl 3764 benzyl *4-(N,N- dimethylami.no)ph enylmethyl" i3obutyl n-butyl 3765 1- pyrolylmethyl benzyl isobutyl n-butyl 3766 1- 162 Table 6 l-pyrolylmethyl isobutyl LV 10096 n-butyl 3767 pyrazolylmethy 1 1- 1- isobutyl n-butyl 3768 imidazolylmeth yi 1- pyrazolylmethyl 1- isobutyl n-butyl 3769 indolylmethyl 1- imida zolylmethyl l-indolylmethyl isobutyl n-butyl 3770 triazolyl®ethy 1 1- 1- isobutyl n-butyl 3771 tetrazolylmeth yi 2- triazolylmethyl 1- isobutyl n-butyl 3772 pyridylmethyl 3- tetrazolylmethyl 2-pyridylmethyl isobutyl n-butyl 3773 pyridylmethyl 4- 3-pyridylmethyl isobutyl n-butyl 3774 pyridylmethyl cyclohexylmeth 4-pyridylmethyl isobutyl n-butyl 3775 yi 2- cyclohexylmethyl isobutyl n-butyl 3776 naphthylmethyl 3- 2-naphthylmethyl isobutyl n-butyl 3777 naphthylmethyl 2- 3-naphthylmethyl isobutyl n-butyl 3778 thiophenylmeth yi 4 — (1 — 2- isobutyl n-butyl 3779 methyl)piperid inyl-methyl "(3,4- thiophenylinethyl 4 - (1— iaobutyl n-butyl 3780 methylenedioxy phenyl)methyl" 2- methyl)piperidin yl-methyl "(3,4- isobutyl n-butyl 3781 thienylmethyl 4- methylenedioxyph enyl)methyl" 2-thienylmethyl iaobutyl n-butyl 3782 biphenylmethyl pyrimidinylmet 4-biphenylmethyl iaobutyl n-butyl 3783 hyl 2- pyrimidinylmethy iaobutyl n-butyl 3784 benzothiazolyl methyl 2- 1 2- iaobutyl n-butyl 3785 benzothlopheny lmethyl 2- benzothiazolylme thyl 2- isobutyl n-butyl 3786 thiomethylethy 1 2- benzothiophenylm ethyl 2- lsobutyl n-butyl 3787 thiomethylmeth yi 2-methylpropyl thiomethyletbyl 2- iaobutyl n-butyl 3788 2-methylbutyl thiomethylmethyl 2-methylpropyl lsobutyl n-butyl 163

Table 6 3789 3-methylbutyl 2-methylbutyl isobutyl n-butyl 3790 cyclopropylmet hyl 3-methylbutyl iaobutyl n-butyl 3791 cyclobutylmeth yi cyclopropylmethy 1 iaobutyl n-butyl 3792 cyclopentylmet hyl cyclobutylmethyl iaobutyl n-butyl 3793 p- hydroxyphenyl- methyl cyclopentylmethy 1 isobutyl n-butyl 3794 p- nitrophenylmet hyl p-hydroxyphenyl- methyl iaobutyl n-butyl 3795 p-aminophenyl- xnethyl P“ nitrophenylmethy 1 isobutyl n-butyl 3796 "4-(N,N- dimethylamino) phenylmethyl" * p-amlnophenyl- methyl iaobutyl n-butyl 3797 benzyl "4-(N,N- dimethylamino)ph enylmethyl" 2-butyl iaobutyl 3798 1- pyrolylmethyl benzyl 2-butyl iaobutyl 3799 1- pyrazolylmethy 1 l-pyrolylroethyl 2-butyl iaobutyl 3800 1- ifliidazolylmeth yi 1- pyrazolylmethyl 2-butyl iaobutyl 3801 1- indolylmethyl 1- imidazolylmethyl 2-butyl isobutyl 3802 1- triazolylmethy 1 l-indolylmethyl 2-butyl isobutyl 3803 * 1- tetrazolylmeth yi 1- triazolylmethyl 2-butyl isobutyl 3804 2- pyridylmethyl 1- tetrazolylmethyl 2-butyl iaobutyl 3805 3- pyridylmethyl 2-pyridylmethyl 2-butyl iaobutyl 3806 4- pyridylmethyl 3-pyridylmethyl 2-butyl iaobutyl 3807 cyclohexylmeth yi 4-pyridylmethyl 2-butyl iaobutyl 3808 2- naphthylxoethyl cyclohexylmethyl 2-butyl iaobutyl 3809 3- naphthylmethyl 2-naphthylmethyl 2-butyl laobutyl 3810 2- thiophenylmeth yi 3-naphthylnvethyl 2-butyl iaobutyl 3811 4-{l- 2- 2-butyl iaobutyl methyl)piperid thiophenylmethyl inyl-methyl 165 LV 10096

Table 6 3835 1- triazolylmethy ļ 1 -indolyljnethyl "3,3- diroethallyl" 2-butyl 3836 X 1- tetrazolylmeth yi 1- triazolylinethyl "3,3-· dimethallyl" 2-butyl 3837 2- pyridylmethyl 1- tetrazolylmethyl "3,3- dimethallyl" 2-butyl 3838 3- pyridylroethyl 2-pyridylmethyl "3,3- dimethallyl" 2-butyl 3839 4- pyridylmethyl 3-pyridylmethyl "3,3- dimethallyl" 2-butyl 3840 cyclohexyljneth yi 4-pyridylmethyl "3,3- dimethallyl" 2-butyl 3841 2- naphthylmethyl cyclohexylmethyl "3,3- dimethallyl" 2-butyl 3842 3- naphthylmethyl 2-naphthylmethyl "3,3- dimethallyl" 2-butyl 3643 2- thiophenylmeth yi 3-naphthylmethyl "3,3- dimethallyl" 2-butyl 3844 4-(l- methyl)piperid inyl-methyl 2- thiophenylmethyl "3,3- dimethallyl" 2-butyl 3845 "(3,4- methylenedioxy phenyl)methyl" 4- (1- methyl)piperidin yl-methyl "3,3- dimethallyl" 2-butyl 3846 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" "3,3- dimethallyl" 2-butyl 3847 4- biphenylmethyl 2-thienylmethyl "3,3- dimethallyl" 2-butyl 3648 pyr imid iny lme t hyl 4-biphenylmethyl "3,3- dimethallyl" 2-butyl 3849 2- benzothlazolyl methyl pyrimidinylmethy 1 "3,3- dimethallyl" 2-butyl 3850 2- benzothiopheny lmethyl 2- benzothiazolylme thyl "3,3- dimethallyl" 2-butyl 3851 2- thiomethylethy 1 2- benzothiophenylm ethyl "3,3- dimethallyl" 2-butyl 3852 2- thiomethylmeth yi 2- thiomethylethyl "3,3- dimethallyl" 2-butyl 3853 2-methylpropyl 2- thiomethylroethyl "3,3- dimethallyl" 2-butyl 3854 2-roethylbutyl 2-methylpropyl "3,3- dimethallyl" 2-butyl 3855 3-methylbutyl 2-methylbutyl "3,3- diwethallyl" 2-butyl 3856 cyclopropylmet hyl 3-methylbutyl "3,3- dlmethallyl" 2-butyl 3857 cyclobutylmeth yi cyclopropylmethy 1 "3,3- dimethallyl" 2-butyl 167

Table 6 3880 4- biphenylmethyl 2-thienylmethyl 3-methallyl "3,3- dirnethallyl 3881 pyrimidinyl- methyl 4-biphenylroethyl 3-methallyl "3,3- dimethallyl 3882 2- benzothiazolyl metbyl pyrimidinylmethy 1 3-methallyl "3,3- dimethallyl 3883- 2-benzothio- phenylmethyl 2- benzothiazolylne thyl 3-methallyl "3,3- dimethallyl' 3884 2-thiomethyl- ethyl 2- benzothlophenyla ethyl 3-methallyl "3,3- dimethallyl' 3885 2-thiomethyl- methyl 2- thiomethylethyl 3-methallyl "3,3- dimethallyl' 3886 2-methylpropyl 2- thiomethylmethyl 3-methallyl "3,3- dimethallyl' 3887 2-methylbutyl 2-rtvethylpropyl 3-methallyl "3,3- dimethallyl' 3888 3-methylbutyl 2-methylbutyl 3-methallyl "3,3- dimethallyl' 3889 cyclopropylmet hyl 3-methylbutyl 3-methallyl "3,3- dimethallyl' 3890 cyclobutylmeth yi cyclopropylmethy 1 3-methallyl "3,3- dimethallyl' 3891 cyclopentylmet hyl cyclobutylmethyl 3-methallyl "3,3- dimethallyr 3892 P" hydroxyphenyl- jnethyl cyclopentylnvethy 1 3-methallyl "3,3- dimethallyl' 3893 P” nitrophenylmet hyl p-hydroxyphenyl- methyl 3-methallyl "3,3- dimethallyl' 3894 p-aminophenyl- methyl p- nitrophenylmethy 1 3-methallyl "3,3- dinvethallyl' 3895 "4-(N,N- dimethylamino) phenylmethyl" X p-aminophenyl- methyl 3-methallyl "3,3- dimethallyl' 3896 benzyl "4-(N,N- dimethylami.no)ph enylmethyl" 2-methallyl 3-methallyl 3897 1- pyrolylmethyl benzyl 2-methallyl 3-methallyl 3898 l-pyrazolyl- nvethyl l-pyrolylmethyl 2-methallyl 3-methallyl 3899 l-ijnida*olyl- methyl 1· pyrazolylmethyl 2-methallyl 3-methallyl 3900 1- indolylmethyl 1- imidazolylmethyl 2-methallyl 3-methallyl 3901 l-triazolyl- methyl l-indolylmethyl 2-methallyl 3-methallyl 3902 l-tetrazolyl- methyl 1· triazolylmethyl 2-methallyl 3-nvethallyl 3903 2- pyridylmethyl 1- tetrazolylmethyl 2-nvethallyl 3-methallyl 168 LV 10096

Table 6 3904 ' 3- pyridylmethyl 2-pyridylmethyl 2-methallyl 3-methallyl 3905 4- pyridylmethyl 3-pyridylroethyl 2-methallyl 3-methallyl 3906 cyclohexyl- methyl 4-pyridylmethyl 2-methallyl 3-methallyl 3907 2- naphthylmethyl cyclohexylmethyl 2-methallyl 3-methallyl 3908 3- naphthylmethyl 2-naphthylmethyl 2-nvethallyl 3-methallyl 3909 2-thiophenyl- methyl 3-naphthylmethyl 2-methallyl 3-methallyl 3910 4-(l-methyl)- piperidinyl- methyl 2- thiophenylmethyl 2-methallyl 3-methallyl 3911 "(3,4- methylenedioxy phenyl)methyl" 4-(l- methyl)piperidin yl-methyl 2-methallyl 3-methallyl 3912 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" 2-roethallyl 3-methallyl 3913 4- biphenylmethyl 2-thienylmethyl 2-methallyl 3-methallyl 3914 pyrimidinylmet hyl 4-bipheny lmethyl 2-methallyl 3-methallyl 3915 2- benzothiazolyl methyl pyrimidinylmethy 1 2-methallyl 3-methallyl 3916 2- benzothiopheny lmethyl 2- benzothiazolylme thyl 2-methallyl 3-roethallyl 3917 2- thiomethylethy 1 2- benzothiophenylm ethyl 2-methallyl 3-methallyl 3918 2-thiomethyl- methyl 2- thiomethylethyl 2-methallyl 3-methallyl 3919 2-rvethylpropyļ 2 - thiomethylmethyl 2-methallyl 3-methallyl 3920 2-methylbutyl 2-methylpropyl 2-methallyl 3-roethallyl 3921 3-methylbutyl 2-methylbutyl 2-methallyl ,3-®ethallyl 3922 cyclopropyl- methyl 3-methylbutyl 2-methallyl 3-methallyl 3923 cyclobutyl- methyl cyclopropyl- methyl 2-methallyl 3-methallyl 3924 cyclopentyl- methyl cyclobutylmethyl 2-methallyl 3-methallyl 3925 p- hydroxyphenyl- methyl cyclopentyl- methyl 2-methallyl 3-methallyl 3926 p-nitrophenyl- methyl p-hydroxyphenyl- methyl 2-methallyl 3-methallyl 3927 p-aminophenyl- methyl p- nitrophenylmethy 1 2-methallyl 3-methallyl 3928 "4-(H,N- X p-aminophenyl- 2-methallyl 3-methallyl dimethylaml.no) methyl phenylmethyl· 169 Table 6 3929 benzyl "4-(N,N-dimethylamino)-phenylmethyl" 2-propyl 2-aethallyl 3930 1- pyrolylmethyl benzyl 2-propyl 2-methallyl 3931 l-pyrazolyl- methyl l-pyrolylmethyl 2-propyl 2-methallyl 3932 l-imidazolyl- methyl 1- pyrazolyln\ethyl 2-propyl 2-methallyl 3933 1- indolylmethyl 1- imidazolylnvethyl 2-propyl 2-methallyl 3934 1- triazolyl»ethy 1 l-indolylmethyl 2-propyl 2-oethallyl 3935 JL 1- tetrazolylmeth yi 2- pyridylmethyl 1- triazolylmethyl 2-propyl 2-nethallyl 3936 1- tetrazolylmethyl 2-propyl 2-nvethallyl 3937 3- pyridylmethyl 2-pyridylmethyl 2-propyl 2-rnethallyl 3938 4- pyridylmethyl 3-pyridylmethyl 2-propyl 2-methallyl 3939 cyclohexyl- methyl 4-pyrldylmethyl 2-propyl 2-methallyl 3940 2- naphthylinethyl cyclohexylmethyl 2-propyl 2-methallyl 3941 3- naphthylmethyl 2-naphthylmethyl 2-propyl 2-methallyl 3942 2-thiophenyl- methyl 3-naphthylmethyl 2-propyl 2-methallyl 3943 4-(l-methyl)- piperidinyl- methyl 2- thiophenylmethyl 2-propyl 2-methallyl 3944 "(3,4- methylenedioxy phenyl)methyl" 4-(l-methyl)- piperidinyl- xnethyl 2-propyl 2-methallyl 3945 2- thienylmethyl "(3# 4- methylenedioxy- phenyl)methyl" 2-propyl 2-methallyl 3946 4- biphenylmethyl 2-thienylmethyl 2-propyl 2-methallyl 3947 pyrimidinyl- methyl 4-biphenylmethyl 2-propyl 2-roethallyl 3948 2- benzothiazolyl methyl pyrimidinyl- methyl 2-propyl 2-methallyl 3949 2-benzothio- phenylmethyl 2- benzothiazolyl- methyl 2-propyl 2-methallyl 3950 2-thio- methylethyl 2- benzothiophenyl- methyl 2-propyl 2-raethallyl 3951 2-thio- methylmethyl 2- thiomethylethyl 2**propyl 2-roethallyl 3952 2-methylpropyl 2- thiomethylmethyl 2-propyl 2-methallyl / 170

Table 6 2-methylbutyl 2-roethylpropyl 2-propyl 3-methylbutyl 2-methylbutyl 2-propyl cyclopropyljnet 3-methylbutyl 2-propyl hyl cyclobutylmeth cyclopropylmethy 2-propyl yi 1 cyclopentylroet hyl cyclobutylxnethyl 2-propyl p- cyclopentylmethy 2-propyl hydroxyphenyl- methyl 1 P* p-hydroxyphenyl- 2-propyl nitrophenylmet nethyl hyl • p-ajninophenyl- p-nitrophenyl- 2-propyl methyl methyl "4-(N,N- p-aminophenyl- 2-propyl dimethylamino) methyl phenylmethyl" benzyl "4-(N,N-dimethylami.no)-phenylmethyl". cyclopropyl 1- pyrolylmethyl benzyl cyclopropyl l-pyrazolyl- methyl l-pyrolylmethyl cyclopropyl l-imidazolyl- 1- cyclopropyl methyl pyrazolylmethyl 1- 1- cyclopropyl indolylmethyl imida zolylmethyl l-triazolyl- methyl l-indolylmethyl cyclopropyl l-tetrazolyl- 1- cyclopropyl methyl triazolylmethyl 2* 1- cyclopropyl pyridylmethyl tetrazolylmethyl 3- pyridylmethyl 2-pyridylmethyl cycloptopyl 4- pyridylmethyl 3-pyridylmethyl cyclopropyl cyclohexyl- methyl 4-pyridylmethyl cyclopropyl 2- naphthylmethyl cyclohexylmethyl cyclopropyl 3- naphthylmethyl 2-naphthylmethyl cyclopropyl 2- thiophenylmeth yi 3-naphthylmethyl cyclopropyl 4-<l- 2- cyclopropyl methyl)piperid inyl-methyl thiophenylmethyl "(3,4- 4-(l-methyl)- cyclopropyl methylenedioxy piperidinyl- phenyl)inethyl· methyl ηι

Table 6 3976 2- thienylroethyl "(3,4- xoethylenedioxyph enyl)methyl" cyclopropyl 2-propyl 3979 4- biphenylmethyl 2-thienylnvethyl cyclopropyl 2-propyl 3960 pyrimidinyl- methyl 4-biphenylwethyl cyclopropyl 2-propyl 3981 2- benzothiazolyl rtvethyl pyrimidinyl- nethyl cyclopropyl 2-propyl 3982 2-benzothio- phenylmethyl 2- benzothiazolyl- methyl cyclopropyl 2-ptopyl 3983 2-thlo- roethylethyl 2- benzothiophenyla ethyl cyclopropyl 2-propyl 3984 2-thio- itvethylmethyl 2- thiomethylethyl cyclopropyl 2-propyl 3985 2-methylpropyl 2- thiomethyLnethyl cyclopropyl 2-propyl 3986 2-methylbutyl 2-methylpropyl cyclopropyl 2-propyl 3987 3-methylbutyl 2-methylbutyl cyclopzopyl 2-propyl 3988 cyclopropylmet hyl 3-methylbutyl cyclopropyl 2-propyl 3989 cyclobutyl»eth yi cyclopropyl- methyl cyclopropyl 2-propyl 3990 cyclopentylmet hyl cyclobutylmethyl cyclopropyl 2-propyl 3991 P* hydroxyphenyl- methyl cyclopentylmethy 1 cyclopropyl 2-propyl 3992 p- nitrophenylmet hyl p-hydroxyphenyl- methyl cyclopropyl 2-propyl 3993 p-aminophenyl- methyl p- nitrophenylmethy ' 1 cyclopropyl 2-propyl 3994 •4-(N,H- X p-aminophenyl- cyclopropyl 2-propyl dlmethylamlno) phenylmethyl* ®ethyl 3995 benzyl "4-(N,N- dimethylami.no)ph enylmethyl* cyclopropyl- methyl cyclopropyl 3996 1* pyrolylnethyl benzyl cyclopropyl- methyl cyclopropyl 3997 l-pyrazolyl- methyl l-pyrolylraethyl cyclopropyl- methyl cyclopropyl 3998 l-imidazolyl- methyl 1- pyrazolyLmethyl cycloptopyl- methyl cyclopropyl 3999 1- indolylmethyl 1- imldazolylmethyl cyclopropyl- methyl cyclopropyl 4000 l-triazolyl- methyl l-indolylmethyl cyclopropyl- methyl cyclopropyl 4001 l-tetrazolyl- 1- cyclopropyl- cyclopropyl methyl triazolylmethyl methyl 4002 2- pyridylmethyl 1- tetrazolylmethyl cyclopropyl- methyl cyclopcopyl 172 3- Table 6 2-pyridylmethyl cyclopropyl- pyridylmethyl methyl- 4- 3-pyridyljnethyl cyclopropylmet pyridylmethyl hyl cyclohexyl- 4-pyridylmethyl cyclopropyl- methyl methyl 2- cyclohexylmethyl cyclopropyl- naphthylmethyl methyl 3- 2-naphthylmethy1 cyclopropylmet naphthylrrvethyl hyl 2-thiophenyl- 3-naphthylmethyl cyclopropyl- 2Dethyl methyl 4-(l-methyl)- 2-thiophenyl- cyclopropyl- piperidinyl- methyl methyl methyl *0,4- 4- (l-nvethyl) - cyclopropyl- methylenedioxy piperidinyl- methyl phenyl)methyl" methyl 2- •0,4- cyclopropyl- thienylmethyl methy1enedioxyph methyl 4- enyl)methyl" 2-thienylmethyl cyclopropyl- biphenylroethyl methyl pyrimidinyl- 4-bipheny lmethy1 cyclopropyl- methyl methyl 2- pyrimidinylmethy cyclopropyl- benzothiazolyl 1 methyl inethyl 2-benzothio- 2-benzo- cyclopropyl- phenylmethyl thiazolyl-methyl methyl 2-thiomethyl- 2-benzo- cyclopropyl- ethyl thiophenylmethyl methyl 2- 2- cyclopropyl- thiomethylmeth yi 2-methylpropyl thiomethylethyl methyl 2- cyclopropyl- thiomethylmethyl methyl 2-methylbutyl 2-methylpropyl cyclopropyl- 3-methylbutyl 2-methylbutyl methyl cyclopropyl- cyclopropyl- 3-methylbutyl methyl Cyclopropyl- methyl methyl cyclobutyl- cyclopropyl- cyclopropyl- methyl methyl methyl cyclopentyl- cyclobutyl- cyclopropyl- methyl methyl methyl p- cyclopentyl- cyclopropyl- hydroxyphenyl- methyl methyl methyl p-nitrophenyl- p-hydroxyphenyl- cyclopropylroet methyl methyl hyl p-aminophenyl- p-nitrophenyl- cyclopropyl- methyl methyl nvethyl 4-{N,N-di- p-aminophenyl- cyclopropyl- jnethyl-ami.no)- methyl methyl phenyl-methyl* 173

Table 6 4028 benzyl "4-(N,N-dinethylami.no)-phenylmethyl" n-pentyl cyclopropylmeth yi 4029 1- pyrolylmethyl benzyl n-pentyl cyclopropylnveth yi 4030 1- l-pyrolylmethyl n-pentyl cyclopropylmeth - pyrazolylroethy 1 yi 4031 * 1- imidazolylmeth yi 1- indolylmethyl 1- pyrazolylmethyl n-pentyl cyclopropylmeth yi 4032 1- imidazolylmethyl n-pentyl cyclopropylmeth yi 4033 1- triazolylroethy l-indolylmethyl n-pentyl cyclopropylmeth yi 4034 X 1- tetrazolylmeth yi 2- pyridylmethyl 1- triazolylmethyl n-pentyl cyclopropylmeth yi 4035 1- tetrazolylroethyl n-pentyl cyclopropylmeth yi 4036 3- pyridylmethyl 2-pyridylmethyl n-pentyl cyclopropylmeth yi 4037 4- pyridylmethyl 3-pyridylmethyl n-pentyl cyclopropylmeth yi 4038 cyclohexylroeth yi 4-pyridylmethyl n-pentyl cyclopropylmeth yi 4039 2- naphthylxnethyl cyclohexylroethyl n-pentyl cyclopropylroeth yi 4040 3- naphthylmethyl 2-naphthylmethyl n-pentyl cyclopropylmeth yi 4041 2- thiophenylmeth yi 4-(l- 3-naphthylmethyl n-pentyl cyclopropylmeth yi 4042 2- n-pentyl cyclopropylmeth nethyl)plperid inyl-methyl thiophenylmethyl yi 4043 "(3,4- methylenedioxy phenyl)methyl" 4- (1- inethyl) piperidin yl-methyl n-pentyl cyclopropylmeth yi 4044 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" n-pentyl cyclopropylmeth yi 4045 4- biphenylmethyl 2-thienylmethyl n-pentyl cyclopropylme t h yi 4046 pyrioidinylmet hyl 4 -bipheny late thy 1 n-pentyl cyc lopropylmeth yi 4047 2- pyrimidinylmethy n-pentyl cyclopropylmeth benzothlazolyl nethyl 1 yi 4048 2- benzothiopheny lmethyl 2- benzothiazolylme thyl n-pentyl cyclopropylrfeth yi 4049 2- thiomethylethy 1 2- benzothiophenylm «thyl n-pentyl cyclopropylmeth yi 174 LV 10096

Table 6 4050 2- thiojnethyljneth yi 2- thiomethylethyl n-pentyl cyclopropylmeth yi 4051 2-methylpropyl 2- thiomethylmethyl n-p«ntyl cyclopropylmeth yi 4052 2-n*ethylbutyl 2-methylpropyl n-pentyl cyclopropylrneth yi 4053 3-methylbutyl 2-methylbutyl n-pentyl cyclopropylitieth yi 4054 cyclopropylmet hyl 3-nvethylbutyl n-pentyl cyclopropylmeth yi 4055 cyclobutylmeth yi cyclopropylmethy 1 n-pentyl cyclopropylroeth yi 405$ cyclopentylmet hyl cyclobuty.lmethyl n-pentyl cyclopropylmeth yi 4057 p- hydroxyphenyl- methyl cyclopentylmethy 1 n-pentyl cyclopropylroeth yi 4058 p- nitrophenylmet hyl p-hydroxyphenyl- methyl n-pentyl cyclopropylmeth yi 4059 p-aminophenyl- methyl p- nitrophenylmethy 1 n-pentyl cyclopropylmeth yi 4060 "4-(N/N* dimethylamino) phenylmethyl" X p-aminophenyl- methyl n-pentyl cyclopropylmeth yi 4061 benzyl "4-(N,N- dimethylamino)ph enylinethyl" 2-pentyl n-pentyl 4062 1- pyrolylmethyl benzyl 2-pentyl n-pentyl 4063 1- pyrazolylroethy 1 l-pyrolylmethyl 2-pentyl n-pentyl 4064 X 1* imidazolylmeth yi 1- indolylmethyl 1- pyra zolylmethyl 2-pentyl n-pentyl 4065 1· imidazolylmethyl 2-pentyl n-pentyl 4066 1- triazolylmethy 1 1-indolylmethy1 2-pentyl n-pentyl 4067 X 1- tetrazolylmeth yi 1- triazolylmethyl 2-pentyl n-pentyl 4068 2- pyridylmethyl 1- tetrazolyl»ethyl 2-pentyl n-pentyl 4069 3- pyridylmethyl 2-pyridylroethyl 2-pentyl n-pentyl 4070 4- pyridylxnethyl 3-pyridylmethyl 2-pentyl n-pentyl * 4071 cyclohexylmeth yi . 2- naphthylmethyl 4-pyridylroethyl 2-pentyl n-pentyl 4072 cyclohexylmethyl 2-pentyl n-pentyl 175 3- Table 6 2-naphthylmethyl 2-pentyl naphthylmethyl 2- 3-naphthylmethyl 2-pentyl thiophenyl»eth yi 4-u- 2- 2-pentyl methyl)piperid thiophenylmethyl inyl-methyl *(3,4- 4-(1- 2-pentyl methylenedioxy methyl) piperidin phenyl)methyl" yl-roethyl 2- •(3,4- 2-pentyl thienylmethyl roethylenedioxyph 4- enyl)methyl" 2-thienylmethyl 2-pentyl biphenylmethyl pyrimidinylmet 4-biphenylmethyl 2-pentyl hyl 2- pyrimidinylmethy 2-pentyl benzothiazolyl 1 methyl 2- 2- 2-pentyl benzothiopheny benzothiazolylme lmethyl thyl 2- 2- 2-pentyl thiomethylethy benzothiophenylm 1 ethyl 2- 2- 2-pentyl thiomethylaeth thiomethylethyl yi 2-methylpropyl 2- 2-pentyl 2-methylbutyl thiomethylmethyl 2-methylpropyl 2-pentyl 3-methylbutyl 2-methylbutyl 2-pentyl cyclopropylmet 3-methylbutyl 2-pentyl hyl cyclobutylmeth cyclopropylmethy 2-pentyl yi 1 cyclopentylmet cyclobutylmethyl 2-pentyl hyl p- cyclopentylmethy 2-pentyl hydroxyphenyl- 1 methyl p- p-hydroxyphenyl- 2-pentyl nitrophenylmet methyl hyl p-aminophenyl- p- 2-pentyl methyl nitrophenylmethy 1 "4- (N,N- X p-amlnophenyl- 2-pentyl diroethylami.no) methyl phenylmethyl· benzyl “4-(N,N- 3-pentyl 1- dimethylamino) ph enylmethyl" benzyl 3-pentyl pyrolylmethyl 176 LV 10096

Table 6 4096 1- pyrazolylmethy 1 l-pyrolylmethyl 3-pentyl 2-pentyl 4097 X 1- imidazolylmeth yi 1- pyrazolylmethyl 3-pentyl 2-pentyl 4098 1- indolylmethyl 1- ūnidazolylinethyl 3-pentyl 2-pentyl 4099 1- triazolylmethy 1 l-indolylmethyl 3-pentyl 2-pentyl 4100 X 1- tetrazolylmeth yi 1- triazolylnethyl 3-pentyl 2-pentyl 4101 2- pyridylmethyl 1- tetrazolylroethyl 3-pentyl 2-pentyl 4102 3- pyridylmethyl 2-pyridylmethyl 3-pentyl 2-pentyl 4103 4- pyridylmethyl 3-pyridylmethyl 3-pentyl 2-pentyl 4104 cyclohexylmeth yi 4-pyridylmethyl 3-pentyl 2-pentyl 4105 2- naphthylroethyl cyclohexylmethyl 3-pentyl 2-pentyl 4106 3- naphthylmethyl 2-naphthylmethyl 3-pentyl 2-pentyl 4107 2- thiophenylmeth yx 3-naphthylmethyl 3-pentyl 2-pentyl 4108 4- (1* methyl)piperid inyl-methyl 2- thiophenylmethyl 3-pentyl 2-pentyl 4109 "(3,4- methylenedioxy phenyl)methyl" 4-(l- nvethyl) piperidin yl-methyl 3-pentyl 2-pentyl 4110 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" 3-p«ntyl 2-pentyl 4111 4- biphenylmethyl 2-thienylmethyl 3-pentyl 2-pentyl 4112 pyrimidinylmet hyl 4-biphenylmethyl 3-pentyl 2-pentyl 4113 2- benzothlazolyl methyl pyrimidinylmethy 1 3-pentyl 2-pentyl 4114 2- benzothiopheny lmethyl 2- benzothiazolylme thyl 3-pentyl 2-pentyl 4115 2- thiomethylethy 1 2- beηzothiopheny1m ethyl 3-pentyl 2-pentyl 4116 2- thioraethylmeth yi 2-methylpropyl 2- thiomethylethyl 3-pentyl 2-pentyl 4117 2- thiomethylmethyl 3-pentyl 2-pentyl 4118 2-methylbutyl 2-methylpropyl 3-pentyl 2-pentyl 177 4119 3-methylbutyl Table 6 2-methylbutyl 3^pentyl 2-pentyl 4120 cyclopropylmet 3-methylbutyl 3-pentyl 2-pentyl 4121 hyl' cyclobutylmeth cyclopropylmethy 3-pentyl 2-pentyl 4122 yi cyclopentylmet 1 cyclobutylmethyl 3-pentyl 2-pentyl 4123 hyl p- cyclopentylmethy 3-pentyl 2-pentyl 4124 hydroxyphenyl- methyl P“ 1 p-hydroxyphenyl- 3-pentyl 2-pentyl 4125 nitrophenylmet hyl p-aminophenyl- methyl p- 3-pentyl 2-pentyl 4126 methyl *4-{N,N- nitrophenyLnethy 1 p-amlnophenyl- 3-pentyl 2-pentyl 4127 dimethylamino) phenylīnethyl" benzyl inethyl "4-(N/N- 3-methyibutyl 3-pentyl 4128 1- dimethylamino)ph enylmethyl" benzyl 3-methylbutyl 3-p«ntyl 4129 pyrolylmethyl 1- l“pyrolylmethyl 3-methylbutyl 3-pentyl 4130 pyrazolylmethy 1 1- 1- 3-methylbutyl 3-pentyl 4131 imidazolylmeth yi 1- pyrazolylmethyl 1- 3-methylbutyl 3-pentyl 4132 indolylmethyl 1- imidazolylmethyl l-indolylmethyl 3-methylbutyl 3-pentyl 4133 triazolylmethy 1 1· 1- 3-methylbutyl 3-pentyl 4134 tetrazolylmeth yi 2- triazolylmethyl 1- 3-methylbutyl 3-pentyl 4135 pyridylmethyl 3- tetrazolylmethyl 2-pyridyl*r>ethyl 3-methylbutyl 3-pentyl 4136 pyridylmethyl 4- 3-pyridylmethyl 3-methylbutyl 3-pentyl 4137 pyridylmethyl cyclohexylmeth 4-pyridylmethyl 3-methylbutyl 3-pentyl 4138 yi 2- cyclohexyl»ethyl 3-methylbutyl 3-pentyl 4139 naphthylroethyl 3- 2-naphthylmethyl 3-®ethylbutyl 3-pentyl 4140 naphthylmethyl 2- 3-naphthylmethyl 3-methylbutyl 3-pentyl 4141 th iophenylmeth yi 4 — (1— 2- 3-methylbutyl 3-pentyl inethyl) piperld inyl-methyl thiophenylmethyl 178 LV 10096

Table 6 4142 •(3,4- methylenedioxy phenyl)methyl" 4-(l- methyl)plperidln yl-methyl 3-inethylbutyl 3-pentyl 4143 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" 3-methylbutyl 3-pentyl 4144 4- 2-thienylmethyl 3-methylbutyl 3-pentyl - biphenylmethyl 4145 pyrimidinyl»et hyl 4-biphenylaethyl 3-methylbutyl 3-pentyl 4145 2- benzothiazolyl methyl pyrimidinylmethy 1 3-methylbutyl 3-pentyl 4147 2- benzothlopheny lmethyl 2- ' benzothiazolylne thyl 3-methylbutyl 3-pentyl 4148 2- thiomethylethy 1 2- benzothiophenylm ethyl 3-methylbutyl 3-pentyl 4149 2- thiomethylmeth yi 2-methylpropyl 2- thiomethylethyl 3-methylbutyl 3-pentyl 4150 2- thiomethylmethyl 3-methylbutyl 3-pentyl 4151 2-methylbutyl 2-methylpropyl 3-methylbutyl 3-pentyl 4152 3-methylbutyl 2-methylbutyl 3-methylbutyl 3-pentyl 4153 cyclopropylmet hyl 3-methylbutyl 3-methylbutyl 3-pentyl 4154 cyclobutylmeth yi cyclopropylmethy 1 3-methylbutyl 3-pentyl 4155 cyclopentylmet hyl cyclobutylmethyl 3-methylbutyl 3-pentyl 4155 p- hydroxyphenyl- xnethyl cyclopentylmethy 1 3-methylbutyl 3-pentyl 4157 p- nitrophenylroet hyl p-hydroxyphenyl-methyl 3-methylbutyl 3-pentyl 4158 p-aminophenyl- xnethyl P“ nitrophenylmethy 3-methylbutyl 3-pentyl 4159 •4-(N,N- dimethylami.no) phenylmethyl" J» p-aminophenyl- methyl 3-methylbutyl 3-pentyl 4160 benzyl "4-(N,N- dimethylamino)ph enylmethyl" 2-methylbutyl 3-methylbutyl 4161 1- pyrolylmethyl benzyl 2-methylbutyl 3-methylbutyl 4162 1- pyra zolyLnethy 1 l-pyrolylmethyl 2-inethylbutyl 3-methylbutyl 4163 X 1- imidazolylmeth yi 1- indolylmethyl 1- pyrazolylmethyl 2-tnethylbutyl 3-methylbutyl 4164 ’l- imidazolylmethyl 2-methylbutyl 3-methylbutyl 179

Table 6 4165 1- triazolylmethy l-indolylmethyl 2-methylbutyl 3-jnethylbutyl 4166 X 1- tetrazolylmeth yi 2- pyridylmethyl 1- triazolylmethyl 2-oethylbutyl 3-methylbutyl 4167 1- tetrazolylmethyl 2-methylbutyl 3-methylbutyl 4168 3- pyridylmethyl 2-pyridylinethyl 2-methylbutyl 3-methylbutyl 4169 4- pyridylxnethyl 3-pyridylmethyl 2-methylbutyl 3-roethylbutyl 4170 cyclohexylmeth yi 2- naphthylroethyl 4-py r idylmethyl 2-methylbutyl 3-methylbutyl 4171 cyclohexylmethyl 2-methylbutyl 3-methylbutyl 4172 3- naphthylmethyl 2-naphthylmethy1 2-methylbutyl 3-methylbutyl 4173 2- thiophenylmeth yi 4-(1- methyl)piperid inyl-methyl 3-naphthylmethyl 2-methylbutyl 3-methylbutyl 4174 2- thiophenylmethyl 2-roethylbutyl 3-methylbutyl 4175 "(3,4- inethylenedioxy phenyl)methyl" 4- (1- methyl)piperidin yl-methyl 2-methylbutyl 3-»ethylbutyl 4176 2- thienylroethyl "(3,4- methylenedioxyph enyl)methyl" 2-®ethylbutyl 3-methylbutyl 4177 4- biphenylmethyl 2-thienylmethyl 2-methylbutyl 3-roethylbutyl 4178 pyrimidinylmet hyl 4-biphenylmethyl 2-methylbutyl 3-methylbutyl 4179 2- benzothiazolyl nvethyl pyrimidinylmethy 1 2-methylbutyl 3-methylbutyl 4180 2- benzothiopheny lmethyl 2- benzothiazolylme thyl 2-methylbutyl 3-methylbutyl 4181 2- thiomethylethy 1 2 - benzothiophenyln ethyl 2-methylbutyl 3-methylbutyl 4182 2- thionvethylmeth yi 2-inethylpropyl 2- thiomethylethyl 2-methylbutyl 3-methylbutyl 4183 2- thiomethylmethyl 2-methylbutyl 3-methylbutyl 4184 2-methylbutyl 2-methylpropyl 2-methylbutyl 3-methylbutyl 4185 3-methylbutyl 2-methylbutyl 2-methylbutyl 3-methylbutyl 4186 cyclopropylmet hyl 3-methylbutyl 2-oethylbutyl 3-methylbut^l 4187 cyclobutylmeth yi cyclopropylmethy 1 2-methylbutyl 3-methylbutyl 4188 cyclopentylmet cyclobutylroethyl 2-methylbutyl 3-nethylbutyl hyl 180 LV 10096

Table 6 4169 p- hydroxyphenyl- methyl cyclopentylmethy 1 2-methylbutyl 3-methylbutyl 4190 p- nitrophenylmet hyl p-hydroxyphenyl- methyl 2-methylbutyl 3-aethylbutyl 4191 * p-amin©phenyl- methyl p- nitropheny lmethy 2-methylbutyl 3-methylbutyl 4192 "4-(N,N- dimethylami.no) phenylmethyl" X p-aminophenyl- methyl 2-methylbutyl 3-methylbutyl 4193 benzyl "4-(K,N- dimethylamino)ph enylmethyl* propargyl 2-aethylbutyl 4194 1- pyrolylmethyl benzyl propargyl 2-jnethylbutyl 4195 1- pyrazolylmethy 1 l-pyrolylmethyl propargyl 2-methylbutyl 4196 4 1- imidazolylmeth yi 1- indolylmethyl 1- pyrazolylraethyl propargyl 2-methylbutyl 4197 1- imidazolylmethyl propargyl 2-methylbutyl 4198 1- triazolylmethy l-indolylmethyl propargyl 2-methylbutyl 4199 X 1- tetrazolylroeth yi 2- pyridyl»ethyl 1- tciazolylmethyl propargyl 2-methylbutyl 4200 1- tetrazolylmethyl propargyl 2-methylbutyl 4201 3- pyridylmethyl 2-pyridylmethyl propargyl 2-methylbutyl 4202 4- pyridylmethyl ' 3-pyridylmethy1 propargyl 2-methylbutyl 4203 cy c 1 ohe xy lme th yi 2- naphthylmethyl 4-pyridylmethyl propargyl 2-methylbutyl 4204 cyclohexylmethyl propargyl 2-methylbutyl 4205 3- naphthylaethyl 2-naphthylmethyl propargyl 2-methylbutyl 4206 2- thiophenylmeth yi 3-naphthylroethyl propargyl 2-methylbutyl 4207 4-(l- methyl)piperid inyl-methyl 2- thiophenylinethyl propargyl 2-methylbutyl 4208 "(3,4- methylenedioxy phenyl)methyl" 4 - (1— methyl)pipe ridin yl-inethyl propargyl 2-methylbutyl 4209 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" propargyl 2-roethylbutyl 4210 4- biphenylroethyl 2-thienylmethyl propargyl 2-methylbutyl 181

Table 6 4211 pyrimidinylroet hyl 4-biphenylmethyl propargyl 2-methylbutyl 4212 2- benzothiazolyl methyl pyrimidinylnethy 1 propargyl 2-methylbutyl 4213 2- benzothiopheny linethyl 2- benzothiazolylme thyl propargyl 2-nethylbutyl 4214 2- thiomethylethy 1 2- benzothiophenylm ethyl propargyl 2-nethylbutyl 4215 2- thiomethylmeth yi 2-methylpropyl 2- thioroethylethyl propargyl 2-oethylbutyl 4216 2- t h i onte thy lmethy 1 propargyl 2-methylbutyl 4217 2-methylbutyl 2-methylpropyl propargyl 2-oethylbutyl 4218 3-methylbutyl 2-methylbutyl propargyl 2-aethylbutyl 4219 cyclopropylmet hyl 3-methylbutyl propargyl 2-nethylbutyl 4220 cyclobutylmeth yi cyclopropylmethy 1 propargyl 2-methylbutyl 4221 cyclopentylmet hyl p- hydroxyphenyl- methyl cyclobutylnethyl propargyl 2-methylbutyl 4222 cyclopentylmethy 1 propargyl 2-roethylbutyl 4223 p- nitrophenylmet hyl p-hydroxyphenyl- methyl propargyl 2-methylbutyl 4224 p-aminophenyl-methyl p- nitrophenylmethy propargyl 2-®ethylbutyl 4225 "4-(N,N- dimethylandno) phenylmethyl" X p-aminopheny1-jnethyl propargyl 2-methylbutyl 4226 benzyl "4-(N, K- dimethylamino)ph enylmethyl" cyclobutyl propargyl 4227 1- pyrolylmethyl benzyl cyclobutyl propargyl 4228 1- pyrazolylmethy 1 l-pyrolylmethyl cyclobutyl propargyl 4229 X 1- imidazolylneth yi 1- indolylmethyl 1- pyra zolylmethyl cyclobutyl propargyl 4230 1- imidazolylmethyl cyclobutyl propargyl 4231 1- triazolylmethy 1 1-indolylmethyl cyclobutyl propargyl 4232 X 1- tetrazolylneth yi 1- triazolylmethyl cyclobutyl propargyl 4233 2- pyridylmethyl 1- tetrazolylmethyl cyclobutyl propargyl 182 Table 6 LV 10096 4234 3- pyridylmethyl 2-pyridylmethy1 cyclobutyl propargyl 4235 4- pyridylmethyl 3-pyridylaethyl cyclobutyl propargyl 4236 cyclohexylmeth yi 2- naphthylmethyl 4-pyridylmethyl cyclobutyl propargyl 4237 cyclohexy lmethy1 cyclobutyl propargyl 4236 3- naphthylmethyl 2-naphthylmethy1 cyclobutyl propargyl 4239 2- thiophenylroeth yi 4 - (1— methyl)pip«rld inyl-methyl 3-naphthylmethyl cyclobutyl propargyl 4240 2- thiophenyLnethyl cyclobutyl propargyl 4241 "(3,4- methylenedioxy phenyl)methyl" 4-{l- methyl)piperidin yl-methyl cyclobutyl propargyl 4242 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl· cyclobutyl propargyl 4243 4- biphenylmethyl 2-thienylmethyl cyclobutyl propargyl 4244 pyrimidinylmet hyl 4-biphenylmethy1 cyclobutyl propargyl 4245 2- benzothiazolyl methyl pyrimidinylxnethy 1 cyclobutyl propargyl 4246 2- benzothiopheny lmethyl 2- benzothiazolylme thyl cyclobutyl propargyl 4247 2- thiomethylethy 1 2- benzothiophenyla ethyl cyclobutyl propargyl 4248 2- thiomethylmeth yi 2-methylpropyl .2- thiomethylethyl cyclobutyl propargyl 4249 2- thiomethylroethyl cyclobutyl propargyl 4250 2-methylbutyl 2-methylpropyl cyclobutyl propargyl 4251 3-methylbutyl 2-methylbutyl cyclobutyl propargyl 4252 cyclopropylmet hyl 3-methylbutyl cyclobutyl propargyl 4253 cyclobutylmeth yi cyclopropylmethy 1 cyclobutyl propargyl 4254 cyclopentylmet hyl cyclobutylmethyl cyclobutyl propargyl 4255 p- hydroxyphenyl- nethyl cyclopenty l®ethy 1 cyclobutyl propargyl « 4256 p- nitrophenylmet hyl p-hydroxyphenyl- methyl cyclobutyl propargyl 4257 p-amlnophenyl- methyl p- nltrophenylmethy cyclobutyl propargyl 1 183

Table 6 4258 "4-(N,N- p-aminophenyl- cyclobutyl propargyl dimethylamino) phenylmethyl" methyl 4259 benzyl "4-(N,N- cydobutylmeth cyclobutyl dimethylaraino)ph enylmethyl" yi 4260 1- benzyl cydobutylmeth cyclobutyl • pyrolylmethyl yi 4261 1- l-pyrolylroethyl cydobutylmeth cydobutyl pyrazdylmethy 1 yi 4262 X 1- 1- cydobutylmeth cydobutyl Jjnidazolylmeth yi 1“ pyrazolylmethyl yi 4263 1- cydobutylmeth cydobutyl indolylmethyl inii da zolylmethyl yi 4264 1· 1-indolyl»ethy1 cydobutylmeth cyclobutyl triazolylmethy 1 yi 4265 X l- 1- cyclobutylmeth cyclobutyl tetrazdylmeth yi 2- triazolylnethyl yi 4266 1- cydobutylmeth cyclobutyl pyridylmethyl tetrazolylmethyl yi 4267 3- 2-pyridylmethyl cydobutylmeth cyclobutyl pyridylmethyl yi 4268 4- 3-pyridylmethyl cyclobutylmeth cyclobutyl pyridylmethyl yi 4269 cyclohexylmeth 4-pyridylmethyl cydobutylmeth cyclobutyl yi yi 4270 2- cyclohexylmethyl cyclobutylmeth cyclobutyl naphthylaethyl yi 4271 3· 2-naphthylmethyl cydobutylmeth cydobutyl naphthylmethyl yi 4272 2- thiophenylmeth yl 4-61- 3-naphthylniethyl cyclobutylmeth yi cyclobutyl 4273 2- cyclobutylmeth cyclobutyl methyl)piperid inyl-methyl thiophenylmethyl yi 4274 "(3,4- 4— < 1— cyclobutylmeth cyclobutyl methylenedioxy methyl)piperidin yi phenyl)methyl" yl-methyl 4275 2~ "(3,4- cyclobutylmeth cyclobutyl thienylmethyl methylenedioxyph enyl)methyl" yi 4276 4- 2-thienylmethyl cyclobutylmeth cyclobutyl biphenylroethyl yi 4277 pyrimidinylmet 4-biphenylmethyl cyclobutylmeth cyclobutyl hyl yi 4278 2- pyrimidinylmethy cyclobutylmeth cyclobutyl benzothiazolyl methyl 1 yi 4279 2- 2- cydobutylmeth cyclobutyl benzothiopheny benzothiazolylme yi lmethyl thyl 184 LV 10096

Table 6 4280 2- 2- cyclobutylmeth cyclobutyl thiomethylethy benzothiophenylm yi 1 ethyl cyclobut'ylmeth 4281 2- 2- cyclobutyl thiomethylmeth yi 2-methylpropyl thiomethylethyl yi 4282 2- cyclobutylmeth cyclobutyl thiomethylmethyl yi 4283 2-methylbutyl 2-methylpropyl cyclobutylroeth yi cyclobutylmeth yi cyclobutylmeth cyclobutyl 4284 3-methylbutyl 2-methylbutyl cyclobutyl 4285 cyclopropylJnet 3-methylbutyl cyclobutyl hyl yi 4266 cyclobutylmeth cyclopropylmethy cyclobutylmeth cyclobutyl yi 1 yi 4287 cyclopentylmet cyclobutylmethyl cyclobutylmeth cyclobutyl hyl yi 4288 p- cyclopentylmethy cyclobutylmeth cyclobutyl hydroxyphenyl- methyl 1 yi 4289 p- p-hydroxypheny1- cyclobutylnieth cyclobutyl nitrophenylmet hyl methyl yi 4290 p-aminophenyl- p- cyclobutylmeth cyclobutyl methyl nitrophenylmethy 1 yl 4291 "4-(N,N- X p-aminophenyl- cyclobutylmeth eyclobutyl dimethylami.no) phenylmethyl" methyl yi 4292 benzyl "4-(NfN- cyclopentyl cyclobutylmethy dimethylamino)ph enylmethyl* 1 4293 1- benzyl cyclopentyl cyclobutylmethy pyrolylmethyl 1 4294 1- l-pyrolylmethyl cyclopentyl cyclobutylmethy pyrazolylmethy 1 1 4295 X 1- 1- cyclopentyl cyclobutylmethy imidazolylmeth yi 1- pyrazolylmethyl 1 4296 1- cyclopentyl cyclobutylmethy indolylmethyl imidazolylmethyl 1 4297 1- l~indolylmethyl cyclopentyl cyclobutylmethy triazolylmethy 1 1 4298 X 1- 1- cyclopentyl cyclobutylmethy tet ra zolylmeth yi 2- triazolylmethyl 1 4299 1- cyclopentyl cyclobutylmethy pyridylmethyl tet ra zolylmethy1 1 * 4300 3* 2-pyridylmethyl cyclopentyl cyclobutylmethy pyridylmethyl * 1 4301 4- 3-pyridylmethyl cyclopentyl cyclobutylmethy 4302 pyridylmethyl 1 cyclohexylmeth 4-pyridylmethyl cyclopentyl cyclobutylmethy yi 1 185

Table 6 4303 2- cyclohexylmethyl cyclopentyl cyclobutyljnethy naphthylnethyl 1 4304 3- 2 -naphthylinethy 1 cyclopentyļ cydobutylmethy n aph thylmethy1 1 4305 2- 3-naphthylmethyl cyelopentyl cyclobutylmethy thiophenylroeth 1 yi 4306 4-(l- 2- cyclopentyl cyclobutylmethy methyl)piperid thiophenylmethyl 1 inyl-methyl 4307 •(3,4- 4-(l- cyclopentyl cyclobutylz»ethy »ethylenedioxy methyl)piperidin 1 phenyl)methyl" yl-nethyi 4308 2- "(3,4- cyclopentyl cyclobutylmethy thlenylmethyl methylenedioxyph 1 enyl)methyl" 4309 4- 2-thienylmethyl cyclopentyl cydobutylmethy biphenylmethyl 1 4310 pyrimidinylmet 4-biphenylmethy1 cyclopentyl cydobutylmethy hyl 1 4311 2- pyrimidinylmethy cyclopentyl cyclobutylmethy benzothiazolyl 1 1 nethyl 4312 2- 2- cyclopentyl cyclobutylmethy benzothiopheny benzothiazolylme 1 lmethyl thyl 4313 2- 2- cyclopentyl cyclobutylmethy thiomethylethy benzothiophenylm 1 1 ethyl 4314 2- 2- cyclopentyl cyclobutyljnethy thiomethylmeth vl thiomethylethyl 1 4315 2-methylpropyl 2- cyclopentyl cyclobutylmethy thiomethylmethyl 1 4316 2-methylbutyl 2-methylpropyl cyclopentyl cydobutylmethy 1 4317 3-methylbutyl 2-methylbutyl cyclopentyl X cydobutylroethy 1 4318 cyclopropylmet 3-methylbutyl cyclopentyl X cyclobutylmethy hyl 1 4319 cyclobutylmeth cyclopropylmethy cyclopentyl cydobutyltnethy yi 1 1 4320 cyclopentyljnet cyclobutylmethyl cyclopentyl cydobutylmethy hyl 1 4321 p- cyclopentylmethy cyclopentyl cyclobutylmethy hydroxyphenyl- 1 1 methyl 4322 p- p-hydroxyphenyl- cyclopentyl cyclobutyljnethy nitrophenylmet methyl 1 hyl 4323 p-aminophenyl- P* cyclopentyl cydobutylmethy methyl nitrophenylmethy 1 1 4324 "4-(N,N- X p-andnophenyl- cyclopentyl cyclobutylmethy dinethylanino) methyl 1 phenylmethyl" 186 LV 10096

Table 6 4325 benzyl "4-(N,N- dimethylaml.no)ph enylroethyl* cyclopentylmet hyl cyclopentyl 4326 1- pyrolylmethyl benzyl cyclopeiitylmet hyl cyclopentyl 4327 1- pyrazolylmethy 1 l-pyrolylmethyl cyclopentylmet hyl cyclopentyl 4326 X 1- imidazolylmeth yi 1- indolylmethyl 1- pyrazolylmethyl cyclopentylaet hyl cyclopentyl 4329 1- imidazolylmethyl cyclopentylmet hyl cyclopentyl 4330 1- triazolylinethy 5 l-indolylmethyl cyclopentylmet hyl cyclopentyl 4331 Λ 1- tetrazolylmeth yi 2- pyridylmethyl 1- triazolylmethyl cyclopentyl- methyl cyclopentyl 4332 1- tetrazolylmethyl cyclopentyl- methyl cyclopentyl 4333 3- pyridylmethyl 2-pyridylmethyl cyclopentyl- methyl cyclopentyl 4334 4- pyridylmethyl 3-pyridylmethyl cyclopentyl- roethyl cyclopentyl 4335 cyclohexylroeth yi 4-pyridylmethy1 cyclopentyl- methyl cyclopentyl 4336 2- naphthylmethyl cyclohexylmethyl cyclopentyl- methyl cyclopentyl 4337 3- naphthylmethyl 2-naphthy lmethyl cyclopentyl- methyl cyclopentyl 4338 ’ 2- thiophenylmeth yl 4-a- methyl)piperid. inyl-methyl 3-naphthylmethyl cyclopentyl- methyl cyclopentyl 4339 2- thiophenylmethyl cyclopentyl- methyl cyclopentyl 4340 "(3,4- methylenedioxy phenyl)methyl" 4 - (1 - methyl)piperidin yl-methyl cyclopentyl- methyl cyclopentyl 4341 2- "(3,4- cyclopentyl- cyclopentyl thienylmethyl methylenedioxyph enyl)methyl" methyl 4342 4- biphenyl»ethyl 2-thienylmethyl cyclopentyl- methyl cyclopentyl 4343 pyrimidinylmet hyl 4-biphenylmethyl cyclopentyl- methyl cyclopentyl 4344 2- pyrimidinylmethy cyclopentyl- cyclopentyl benzothiazolyl methyl 1 methyl 4345 2- benzothlopheny lmethyl 2- benzothiazolylme thyl cyclopentylinet hyl cyclopentyl 4346 2- thiomethylethy 1 2- benzothiophenyl- methyl cyclopentyl- methyl cyclopentyl 187

Table 6 4347 2- thiomethyljneth yi 2-methylpropyl 2- thiomethylethyl cyclopentyl- methyl cyclopentyl 4348 2- thiomethylmethyl cyclopentyl- methyl cyclopentyl 4349 2-methylbutyl 2-jnethylpropyl cyclopentyl- methyl cyclopentyl 4350 ' 3-methylbutyl 2-methylbutyl cyclopentyl- methyl cyclopentyl 4351 cyclopropylmet hyl 3-methylbutyl cyclopentyl- methyl cyclopentyl 4352 cyclobutylnveth cyclopropyl- cyclopentyl- cyclopentyl yi methyl nvethyl 4353 cyclopentylmet hyl cyclobutylmethyl cyclopentyl- methyl cyclopentyl 4354 p- hydroxyphenyl- methyl cyclopentyl- methyl cyclopentyl- ®ethyl cyclopentyl 4355 p- nitrophenylmet hyl p-hydroxyphenyl- methyl cyelopentyl- methyl cyclopentyl 4356 p-aminophenyl- methyl p-nitrophenyl- nvethyl cyclopentyl- methyl cyclopentyl 4357 "4-(N,N- dimethylanu.no) phenylmethyl" p-aminophenyl- methyl cyclopentyl- methyl cyclopentyl 4358 benzyl "4-(N,N- dime thy1amino)ph enylmethyl" l-hexyl cyclopenty lmeth yi 4359 1- pyrolylmethyl benzyl l-hexyl cyclopentylmeth yi 4360 1- pyrazolylmethy 1 1-pyrolylmethyl l-hexyl cyclopentylmeth yi 4361 J. 1- imidazolylmeth yi 1- indolylmethyl 1- pyrazolylmethyl l-hexyl cyclopentylmeth y! 4362 1- imida zolylmethyl l-hexyl .cyclopentylmeth yi 4363 1- triazolylmethy l-indolylmethyl l-hexyl cyclopentylineth yi 4364 X 1- tetrazolylmeth yi 2- pyridylmethyl 1- triazolylmethyl l-hexyl cyclopentylmeth yi 4365 1- tetrazolylmethyl l-hexyl cyclopentylmeth yi 4366 3* pyridylmethyl 2-pyridylmethyl l-hexyl cyclopentylmeth yi 4367 4- pyridylmethyl 3-pyridylmethyl l-hexyl cyclopentylmeth yi 4368 cyclohexylroeth yi 4-pyridylmethyl l-hexyl cyclopentylmeth yi 4369 2- naphthylmethyl cyclohexylmethyl l-hexyl cyclopentylmeth yi 4370 3- naphthylmethyl 2-naphthylmethyl l-hexyl cyclopentylmeth yi 188 LV 10096

Table 6 4371 2- thiophenylmeth yi 4 - {1— methyl)plperid inyl-methyl 3-naphthylmethyl l-hexyl cyclopentylmeth yi 4372 2- thiophenylmethyl l-hexyl cyclopentylmeth yi 4373 "(3,4- methylenedioxy phenyl)methyl” 4-(1- methyl)piperidin yl-methyl l-hexyl cyclopentylmeth y! 4374 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" l-hexyl cyclopentylmeth yi 4375 4- biphenylmethyl 2-thienylmethyl l-hexyl cyc1opentylmeth yi 4376 pyrimidinylmet hyl 4-biphenylxnethy 1 l-hexyl cyclopentylmeth yi 4377 2- benzothiazolyl methyl pyriitddinylinethy 1 l-hexyl cyclopentylmeth yi 4378 2- benzothiopheny lroethyl 2- benzothiazolylme thyl l-hexyl cyclopentylmeth yi 4379 2- thiomethylethy 1 2- benzothiophenylm ethyl l-hexyl cyclopentylmeth yi 4380 2- thiomethy lmeth yi 2-methylpropyl 2- thiomethylethyl l-hexyl cyclopentylmeth yl 4361 2- thiomethylmethyl l-hexyl cyclopentylmeth yi 4382 2-methylbutyl 2-methylpropyl l-hexyl cyclopentylmeth yi cyclopentylmeth yi cyclopentylmeth yi 4383 3-methylbutyl 2-methylbutyl l-hexyl 4384 cyclepropylmet hyl 3-methylbutyl l-hexyl 4385 cyclobutylmeth yi cyc’lopropylmethy 1 l-hexyl cyclopentylmeth yi 4386 cyclopentylmet hyl cyclobutylmethyl l-hexyl cyclopentylmeth yi 4387 p- hydroxyphenyl- methyl cyclopentylmethy 1 l-hexyl cyclopentylmeth yi 4388 p- nittophenylmet hyl p-hydroxypheny1-methyl l-hexyl cyclopentylmeth yl 4389 p-aminophenyl- methyl p- nitrophenylmethy l-hexyl cyclopentylmeth yi 4390 •4-(N,N- dimethylami.no) phenylmethyl" * p-aminophenyl- methyl l-hexyl cyclopentylmeth yi 4391 benzyl "4-(N,N- dimethylamino)ph enylmethyl" 4-methylpentyl l-hexyl 4392 1- pyrolylmethyl benzyl 4-methylpentyl l-hexyl 189

Table 6 4393 1- pyrazolylmethy 1 l-pyrolylmethyl 4-methylpentyl l-hexyl 4394 1- imidazolylmeth yi 1- pyrazolylmethyl 4-methylpentyl l-hexyl 4395 1- indolylmethyl 1- imidazolylmethy1 4-methylpentyl l-hexyl 4396 1- triazolylmethy 1 l-indolylmethyl 4-methylpentyl l-hexyl 4397 1- tetrazolylmeth yi 1- triazolylmethyl 4-methylpentyl l-hexyl 4398 2- pyridylroethyl 1- tetrazolylxaethyl 4-methylpentyl l-hexyl 4399 3- pyridylmethyl 2-pyridylroethyl 4-methylpentyl l-hexyl 4400 4- pyridylmethyl 3-pyridylroethyl 4-methylpentyl l-hexyl 4401 cyclohexylmeth yi 2- naphthylmethyl 4-pyridylmethyl 4-methylpentyl l-hexyl 4402 cyclohexylwethyl 4-methylpentyl l-hexyl 4403 3- naphthylmethyl 2-naphthylxnethyl 4-methylpentyl l-hexyl 4404 2- thiophenylmeth yi 4-(l- methyl)piperid inyl-methyl 3-naphthylmethyl 4-methylpentyl l-hexyl 4405 2- thlophenylmethyl 4-methylpentyl l-hexyl 4406 "(3,4- methylenedioxy phenyl)methyl" 4 — {1— methyl)piperidin yl-methyl 4-methylpentyl l-hexyl 4407 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" 4-methylpentyl l-hexyl 4408 4- biphenylmethyl 2-thienylmethyl 4-methylpentyl l-hexyl 4409 pyrinu.dinylmet hyl 4-biphenylmethyl 4-methylpentyl l-hexyl 4410 2- benzothiazolyl methyl pyrimidi nylmethy 1 4-methylpentyl l-hexyl 4411 2- benzothiopheny lmethyl 2- benzothiazolylme thyl 4-methylpentyl l-hexyl 4412 2- thionvethylethy 1 2- benzothiophenyla ethyl 4-methylpentyl l-hexyl 4413 2- thiomethylmeth yi 2- thiomethylethyl 4-methylpentyl l-hexyl 4414 2-methylpropyl 2- th iomethylmethyl 4-methylpentyl l-hexyl 4415 2-methylbutyl 2-methylpropyl 4-methylpentyl l-hexyl LV 10096 4416 3-methylbutyl Table 6 2-methylbutyl 4-methylpentyl l-hexyl 4417 cyclopropylmet 3-methylbutyl. 4-methylpentyl l-hexyl 4418 hyl cyclobutylmeth cyclopropylmethy 4-methylpentyl l-hexyl 4419 yi cyclopentylaet 1 cyclobutylmethyl 4-methylpentyl l-hexyl 4420 hyl p- cyclopentylmethy 4-methylpentyl l-hexyl 4421 hydroxyphenyl- methyl P' 1 p-hydroxyphenyl- 4-methylpentyl l-hexyl 4422 nitrophenylmet hyl p-aitdnophenyl- methyl p-nitrophenyl- 4-methylpentyl l-hexyl 4423 methyl "4-(N,H- methyl p-aminophenyl- 4-methylpentyl l-hexyl 4424 dimethylami.no) phenylmethyl" benzyl methyl *4-(N,lī 3-methylpentyl 4-methylpentyl 4425 l-pyrolyl- ci imethyl-amino) - phenylmethyl" benzyl 3-methylpentyl 4-methylpentyl 4426 methyl l-pyrazolyl· 1-pyrolylmethyl 3-methylpentyl 4-methylpentyl 4427 nvethyl l-invidazolyl- 1- 3-methylpentyl 4-methylpentyl 4428 methyl l-indolyl- pyra zolylmethyl 1- 3-methylpentyl 4-inethylpentyl 4429 methyl l-triazolyl- imida zolylmethyl l-indolylmethyl 3-methylpentyl 4-methylpentyl 4430 methyl l-tetrazolyl- 1- 3-methylpentyl 4-methylpentyl 4431 methyl 2-pyridyl- triazolylmethyl 1- 3-methylpentyl 4-methylpentyl 4432 methyl 3- tetrazolylmethyl 2-pyridylmethyl 3-methylpentyl 4-methylpentyl 4433 pyridylmethyl 4 3-pyridylmethyl 3-methylpentyl 4-methylpentyl 4434 pyridylmethyl cyclohexylmeth yi 2- 4-pyridylmethyl 3-methylpentyl 4-methylpentyl 4435 cyclohexylmethyl 3-methylpentyl 4-methylpentyl 4436 naphthylmethyl 3- 2-naphthylmethyl 3-methylpentyl 4-methylpentyl 4437 naphthylmethyl 2-thiophenyl- 3-naphthylmethyl 3-methylpentyl 4-methylpentyl 4438 methyl 4 - (1- 2- 3-nvethylpentyl 4-methylpentyl 4439 methyl)piperld inyl-methyl "(3,4- thlophenylmethyl 4-(l- 3-methylpentyl 4-methylpenčyl 4440 methylenedioxy phenyl)methyl" 2- methy1)piperidin yl-methyl "(3,4- 3-methylpentyl 4-methylpentyl thienylmethyl methylenedioxyph enyl)methyl" 191

Table 6 4441 4- biphenylmethyl 2-thienylmethyl 3-aethylpentyl 4-methylpentyl 4442 pyrimldinylmet hyl 2- benzothiazolyl methyl 4-biphenylmethyl 3-methylpentyl 4-methylpentyl 4443 pyr imidiny lmethy 1 3-methylpentyl 4-methylpentyl 4444 2· benzothiopheny lmethyl ' 2- benzothiazolylme thyl 3-methylpentyl 4-methylpentyl 4445 2- thiomethylethy 1 2- benzothiophenylm ethyl ’ 3-nethylpentyl 4-methylpentyl 4446 2- thioroethylmeth yi 2-methylpropyl 2- thiomethylethyl 3-methylpentyl 4-methylpentyl 4447 2- thiomethylnethyl .3-methylpentyl 4-methylpentyl 4448 2-methylbutyl 2-methylpropyl 3-methylpentyl 4-methylpentyl 4449 3-methylbutyl 2-nvethylbutyl 3-methylpentyl 4-methylpentyl 4450 cyclopcopylnet hyl 3-methylbutyl 3-methylpentyl 4-wethylpentyl 4451 cyclobutylAeth yi cyclopropylmethy 1 3-methylpentyl 4-methylpentyl 4452 cyclopentylmet hyl cyclobutylmethyl 3-methylpentyl 4-methylpentyl 4453 p- hydroxyphenyl- methyl cyclop«ntyljnethy 1 3-methylpentyl 4-methylpentyl 4454 p- nitrophenyl»et hyl p-hydroxyphenyl- tnethyl 3-methylpentyl 4-methylpentyl 4455 p-aminophenyl- methyl p- nitrophenylmethy 1 3-methylpentyl 4-methylpentyl 4456 •4-(N,N- dimethylamino) phenylmethyl" 4 p-aminophenyl- nethyl 3-methylpentyl 4-methylpentyl 4457 benzyl •4-(N,N- dimethylamino)ph enyln>ethyl" lsopropyl 3-methylpentyl 4458 1- pyrolylmethyl benzyl isopropyl 3-methylpentyl 4459 1- pyrazolylmethy 1 l-pyrolylmethyl isopropyl 3-methy lpenty 1 4460 Jk 1- imidazolyloeth yi 1- indolylmethyl 1- pyrazolylmethyl iaopropyl 3-avethylpentyl 4461 1- imidazolylnvethyl isopropyl 3-®ethylpentyl 4462 1- triazolyloethy 1 1-indolylmethyl isopropyl 3-methylpentyl 4463 1- 1- isopropyl 3-methylp«ntyl tetrazolyLneth triazolylmethyl yl 192 Table 6 LV 10096 4464 2- pyridylmethyl 1- tetrazolylmethyl isopropyl 3-methylpentyl 4465 3- pyridylmethyl 2-pyridylmethyl iaopropyl 3-methylpentyl 4466 4- pyridylmethyl 3-pyridylmethyl isopropyl 3-methylpentyl 4467 cyclohexylmeth yi 2- naphthylmethyl 4-pyridylmethyl isopropyl 3-methylpentyl 4468 cyclohexyLmethyl isopropyl. 3-methylpentyl 4469 3- naphthyl®ethyl 2-naphthylmethyl isopropyl 3-methylpentyl 4470 2- thiophenylmeth yi 4 — (1— methyl)piperid inyl-methyl 3-naphthylmethyl isopropyl 3-methylpentyl 4471 2- thiophenylmethyl isopropyl 3-methylpentyl 4472 "(3,4- methylenedioxy phenyl)methyl" 4-(1- methyl)piperidin yl-xnethyl isopropyl 3-methylpentyl 4473 2- thienylmethyl •{3,4- methylenedioxyph enyl)methyl" iaopropyl 3-methylpentyl 4474 4- biphenylmethyl 2-thienylmethyl iaopropyl 3-methylpentyl 4475 pyrimidinylmet hyl 4-biphenyLmethyl iaopropyl 3-methylpentyl 4476 2- benzothiazolyl methyl pyrimidinylinethy 1 iaopropyl 3-roethylpentyl 4477 2-benzothio- phenylmethyl 2- benzothiazolylme thyl iaopropyl 3-methylpentyl 4478 2-thiomethyl- ethyl 2- benzothiophenylm ethyl iaopropyl 3-methylpentyl 4479 2-thiomethyl- methyl 2- thiomethy1ethy1 iaopropyl 3-methylpentyl 4480 2-methylpropyl 2- thiomethylmethyl iaopropyl 3-methylpentyl 4481 2-methylbutyl 2-methylpropyl iaopropyl 3-methylpentyl 4482 3-methylbutyl 2-methylbutyl isopropyl 3-methylpentyl 4483 cyclopropyl- methyl 3-methylbutyl iaopropyl 3-methylpentyl 4484 cyclobutyl- oethyl cyclopropyl- methyl iaopropyl 3-methylpentyl 4485 cyclopentyl- methyl cyclobutylmethyl iaopropyl 3-methylpentyl 448$ p- hydroxyphenyl- methyl p-nitrophenyl- methyl cyclopentyl- methyl iaopropyl 3-methylpentyl 4487 p-hydroxyphenyl- methyl iaopropyl 3-methylpentyl 4488 p-aminophenyl- methyl p-n it rophenyl-methyl iaopropyl 3-methylpentyl 193

Table 6 4489 "4-(N,W- dimethylami.no) phenylmethyl" p-aminophenyl- methyl iaopropyl 3-methylpentyl 4490 benzyl •4-(N,N- dimethylamino)ph enylmethyl" 3-methylbutyl isopropyl un 1- pyrolylmethyl benzyl 3-methylbutyl isopropyl 4492 l-pyrazolyl- methyl l-pyrolylmethyl 3-methylbutyl iaopropyl 4493 1- imidazolylmeth yi 1- pyrazolylmethyl « 3-®ethylbutyl isopropyl 4494 1- indolylmethyl 1- imidazolylroethyl 3-nvethylbutyl iaopropyl 4495 1- triazolylmethy 1 l-indolylmethyl 3-methylbutyl isopropyl 4496 X 1- tetrazolylmeth yi 2- pyridylroethyl 1- triazolylmethyl 3-roethylbutyl isopropyl 4497 1- tetrazolylmethyl 3-methylbutyl iaopropyl · 4498 3- pyridylmethyl 2-pyridylmethy1 3-methylbutyl isopropyl 4499 4- pyridylmethyl 3-pyridylmethy1 3-methylbutyl isopropyl 4500 cyclohexylmeth yi 2- naphthylmethyl 4-pyridylmethyl 3-methylbutyl iaopropyl 4501 cyclohexylmethyl 3-nvethylbutyl isopropyl 4502 3- naphthylmethyl 2-naphthylmethyl 3-methylbutyl iaopropyl 4503 2- thiophenylmeth yi 4 — (1 - methyl)piperid inyl-methyl 3-naphthylmethyl 3-methylbutyl iaopropyl 4504 2- thiophenylmethyl 3-methylbutyl isopropyl 4505 - (3,4- methylenedioxy phenyl)methyl" 4-(l- methyl)piperidin yl-xnethyl 3-methylbutyl isopropyl 4506 2- thienylmethyl "(3,4- methylenedioxyph enyl)methyl" 3-methylbutyl isopropyl 4507 4- biphenylmethyl 2-thienylmethyl 3-methylbutyl iaopropyl 4508 pyrimidinylmet hyi 2- benzothiazolyl methyl 4-biphenylmethyl 3-methylbutyl isopropyl 4509 pyrimidinylmethy 1 3-xnethylbutyl isopropyl t 4510 2- benzothiopheny lmethyl 2- benzothiazolylme thyl 3~methylbutyl iaopropyl 4511 4512 4513 4514 4515 4516 4517 4518 4519 4520 4521 4522 4523 4524 4525 4526 4527 4528 4529 4530 4531 4532 4533 194 LV 10096 Table 6 2- 2- 3-nvethylbutyl isopropyl thiomethylethy benzothiophenylm 1 2- thioroethylmeth yi 2-methylpropyl ethyl 2- thiomethylethyl 3-methylbutyl isopropyl 2- 3-methylbutyl i3optopyl thiomethylmethyl 2-roethylbutyl 2-methylpropyl 3-methylbutyl i3opropyl 3-methylbutyl 2- -methylbutyl 3-methylbutyl isopropyl cyclopropylmethyl 3-methylbutyl 3-methylbutyl is'opropyl cyclobutylmethyl cyclopropylmethyl 3-methylbutyl iaopropyl cyclopentylmethyl cyclobutyl»ethyl 3-methylbutyl isopropyl P* cyclopentylme 3-methylbutyl lsopropyl hydroxyphenyl thyl -methyl p- p- 3-methylbutyl lsopropyl nitrophenylitve hydroxyphenyl thyl -methyl p- p- 3-methylbutyl isopropyl aminophenyl- nitrophenylme methyl thyl "4-(N,N- p- 3-methylbutyl isopropyl dimethylamino aminophenyl- )phenylmethy1 m methyl benzyl •4-(N,N- 2-phenylethyl 3-methylbutyl dimethylamino )phenylmethyl n 1- benzyl 2-phenylethyl 3-methylbutyl pyrolylmethyl 1« 1- 2-phenylethyl 3-©ethylbutyl pyrazolylmeth pyrolylmethyl yi 1- 1- 2-phenylethyl 3-nvethylbutyl imidazolylmet pyrazolylmeth hyl yi 1~ 1” 2-phenylethyl 3-methylbutyl indolylmethyl imidazolylmet hyl 1- 1- 2-phenylethyl 3-methylbutyl triazolylnveth indolylmethyl yi 1- 1- 2-phenylethyl 3*methylbutyl tetrazolylmet trlazolylmeth hyl yi 2- 1- 2-phenylethyl 3-methylbutyi pyridyl®ethyl tetrazolylmet hyl 3* 2- 2-phenylethyl 3-nethylbutyl pyridylmethyl pyridylmethyl 4- 3- 2-phenylethyl 3-methylbutyl pyridylmethyl pyridylmethyl cyclohexylroet 4- 2-phenylethyl 3-methylbutyl hyl pyrldylmethyl 195

Table 6 4534 2- naphthyla>ethy cyclohexylmet hyl 2-phenyl«thyl 3-methylbutyl 4535 X 3- naphthylinethy ļ 2- naphthylmethy 2-phenylethyl 3-methylbutyl 4536" X 2- thiophenylmet hyl X 3- naphthylmethy 1 2-phenylethyl 3-methylbutyl 4537 4-{l- methyl)piperi dinyl-roethyl 2- thiophenylmet hyļ 2-phenylethyl 3-methylbutyl 4S38 "(3,4- methylenediox yphenyl)roethy 1 ** 4-(l- nethyl)piperi dinyl-methyl 2-phenylethyl 3-methylbutyl 4539 X 2- thienylroethyl "(3,4- methylenediox yphenyl)methy 1 M 2-phenylethyl 3-methylbutyl 4540 4- biphenylmethy 1 X 2- thienylmethyl 2-phenylethyl 3-methylbutyl 4541 X pyrimidinylme thyl 4- biphenylmethy 1 2-phenylethyl 3-n»ethylbutyl 4542 2- benzothiazoly lmethyl X pyrimidinylme thyl 2-phenylethyl 3-nethylbutyl 4543 2- benzothiophen ylmethyl 2- benzothiazoly lmethyl 2-phenylethyl 3-methylbutyl 4544 2- thioroethyleth yi 2- benzothiophen ylmethyl 2-phenylethyl 3-methylbutyl 4545 2- thiomethylmet hyl 2- thiomethyleth yi 2-phenylethyl 3-roethylbutyl 4546 2- methylpropyl 2- thiomethylmet hyl 2-phenylethyl 3-methylbutyl 4547 2-methylbutyl 2- inethylpropyl 2-phenylethyl 3-methylbutyl 4548 3-methylbutyl 2-methylbutyl 2-phenylethyl 3-methylbutyl 4549 cyclopropylme thyl 3-nvethylbutyl 2-phenylethyl 3-methylbutyl 4550 cyclobutylroet hyl cyclopropylme thyl 2-phenylethyl 3-methylbutyl 4551 cyclopentylme thyl cyclobutylmet hyl 2-phenylethyl 3-methylbutyl 4552 p- hydroxyphenyl -methyl cyclopentylme thyl 2-phenylethyl 3-methylbutyl 4553 p- nitrophenylme thyl p- hydroxyphenyl -methyl 2-phenylethyl 3-methylbutyl 196 LV 10096

Table 6 4554 p- p- 2-phenylethyl 3-roethylbutyl aroinophenyl- nitrophenylroe methyl thyl 4555 p- 2-phenylethyl 3-roethylbutyl diroethylaitiino aminophenyl- - )phenyl»ethyl m roethyl 4556 benzyl "4-(N,N- 3- 2-phenylethyl dimethylamino )phenylmethyl •t phenylpropyl 4557 1- benzyl 3- 2-phenylethyl pyrolylroethyl phenylpropyl 4558 1" 1- 3- 2-phenylethyl pyrazolylroeth yi pyrolylmethyl phenylpropyl 4559 1“ 1- 3- 2-phenylethyl imidazolylmet pyrazolylroeth phenylpropyl hyl yi 2-phenylethyl 4560 1- 1* 3- indolylroethyl imidazolylmet hyl phenylpropyl 4561 1- 1- 3- 2-phenylethyl triazolylmeth yi indolylmethyl phenylpropyl 4562 1- 1- 3- 2-phenylethyl tetrazolylmet triazolylroeth phenylpropyl hyl yi 4563 2- 1- 3- 2-phenylethyl pyridylmethyl tetrazolylroet phenylpropyl hyl 2-phenylethyl 4564 3- 2- 3- pyridylmethyl pyridylmethyl phenylpropyl 4565 4 - 3- 3- 2-phenylethyl pyridylroethyl pyridylroethyl phenylpropyl 2-phenylethyl 4566 cyclohexylmet 4- 3- hyl pyridylroethyl phenylpropyl 4567 2- cyclohexylroet 3- 2-phenylethyl naphthylroethy Λ hyl phenylpropyl 4568 •ί 3- 2- 3- 2-phenylethyl naphthylroethy 1 naphthylroethy 1 phenylpropyl 4569 X 2- X 3- 3- 2-phenylethyl thiophenylmet naphthylmethy phenylpropyl hyl 1 4570 4-{l- 2- 3- 2-phenylethyl methyl)piperi thiophenylmet phenylpropyl dinyl-methyl hyl 2-phenylethyl 4571 "(3,4- 4-(1- 3- methylenediox methyl)piperi phenylpropyl yphenyljmethy 1 4* dinyl-methyl 4572 X 2- "(3,4- 3- 2-phenylethyl thienylmethyl methylenediox phenylpropyl yphenyl)methy 1- 197

Table 6 4573 4- 2- 3- 2-phenylethyl biphenylmethy 1 thienylmethyl phenylpropyl 4574 X pyrimidinylme 4- 3- 2-phenylethyl thyl biphenylmethy 1 phenylpropyl 4575 2- X pyrimidinylme 3- 2-phenylethyl benzothiazoly lmethyl thyl phenylpropyl 4576 2- 2- 3- 2-phenylethyl benzothiophen benzothlazoly phenylpropyl ylmethyl lmethyl 4577 2- 2- 3- 2-phenylethyl thiomethyleth benzothiophen phenylpropyl yi ylmethyl 4578 · 2- 2- 3- 2-phenylethyl thiomethylmet thiomethyleth phenylpropyl hyl yi 4579 2- 2- 3- 2-phenylethyl methylpropyl thiomethylmet hyl phenylpropyl 4580 2-methylbutyl 2- 3* 2-phenylethyl methylpropyl phenylpropyl 4581 3-methylbutyl 2-methylbutyl 3· phenylpropyl 2-phenylethyl 4582 cyclopropylme 3-methylbutyl 3- 2-phenylethyl thyl phenylpropyl 4583 cyclobutylmet cyclopropylroe 3- 2-phenylethyl hyl thyl phenylpropyl 4584 cyclopentylme cyclobutylmet 3- 2-phenylethyl thyl hyl phenylpropyl 4585 p- cyclopentylme 3- 2-phenylethyl hydroxyphenyl -methyl thyl phenylpropyl 4586 p- p- 3· 2-phenylethyl nitrophenylme hydroxyphenyl phenylpropyl thyl -methyl 4587 p- p- 3- 2-phenylethyl aminophenyl- nitrophenylme phenylpropyl methyl thyl 4588 "4-(N,K- p- 3“ 2-phenylethyl dimethylanu.no aminophenyl- phenylpropyl )phenylmethyl «1 methyl 4589 benzyl "4-ίΝ,Ν- "2-ίΝ,Ν- 3- dimethylamino dimethylamino phenylpropyl )phenylmethyl «1 )ethyl· 4590 1- benzyl *2-<N,N- 3- pyrolylmethyl dimethylamino )ethyl" phenylpropyl 4591 1- 1- •2-<N,N- 3- pyrazolylmeth pyrolylmethyl dimethylamino phenylpropyl yi )ethyl" 4592 1- 1- "2-{K,N- 3- imidazolylmet pyrazolylmeth dimethylaml.no phenylpropyl hyl yi )ethyl* 198 LV 10096

Table 6 1- . 1- "2-(N,N- 3- indolylmethyl iraidazolylmet dimethylamino phenylpropyl hyl )ethyl": 1- 1- "2-(N,N- 3- triazolylmeth indolyl»ethyl dimethylamino phenylpropyl yi )ethyl" 1- 1- "2-(N,N- 3- tetrazolylmet triazolylsveth dimethylamino phenylpropyl hyl yi )ethyl" 2- 1- *2-{N,N- 3- pyridylmethyl tetrazolylmet dimethylamino phenylpropyl hyl )ethyl" 3- 2- "2-(N,N- 3- pyridylnvethyl pyridylmethyl dimethylamino )ethyl" phenylpropyl 4- 3- "2-{N,N- 3- pyridylmethyl pyridylmethyl dimethylamino )ethyl" phenylpropyl cyclohexylmet 4- "2-(N,N- 3- hyl pyridylmethyl dimethylamino )ethyl" phenylpropyl 2- cyclohexylmet "2-(N,N- 3- naphthylmethy hyl dimethylamino phenylpropyl 1 )ethyl" 3- 2- "2-{N,N- 3- naphthylmethy naphthylmethy dimethylamino phenylpropyl 1 1 )ethyl" 2- 3- "2-(N,N- 3- thiophenylmet naphthylmethy dimethylanu.no phenylpropyl hyl 1 )ethyl" 4 — (1— 2- "2-(N,N- 3- methyl)piperi thiophenylmet dimethylamino phenylpropyl dinyl-methyl hyl Jethyl" "(3,4- 4- (1- "2-{N,N- 3- methylenediox inethyl)piperi dimethylamino phenylpropyl yphenyl)methy 1« dinyl-methyl )ethyl" X 2- . *(3,4- "2-(N,N- 3- thienylmethyl methylenediox dimethylamino phenylpropyl yphenyl)methy )ethyl" 4- X 2- "2-(N,N- 3- biphenylmethy thienylmethyl diroethylamino phenylpropyl 1 )ethyl" pyrimidinylroe 4- "2-{N,N- 3- thyl biphenylmethy dimethylanu.no phenylpropyl 1 )ethyl" 2- pyrimidinyline "2-(N,N- 3- benzothiazoly thyl dimethylamino phenylpropyl lmethyl )ethyl" 2- 2- "2-(K,N- 3- benzothiophen benzothiazoly dimethylamino phenylpropyl ylmethyl lroethyl )ethyl" 2- 2- •2-(N,N- 3- thiomethyleth benzothiophen dimethylamino phenylpropyl yi ylmethyl )ethyl" 199

Table 6 4611 2- 2- "2-<N,N- 3- thiomethylmet thiomethyleth dlmethylamlno phenylpropyl hyl yi )ethyl" 4612 2- 2- "2-(Nf N- 3- methylpropyl thiomethylmet dimethylamino phenylpropyl hyl )ethyl" 4613 2-methylbutyl 2- "2-(N/H- 3- methylpropyl dimethylamino )ethyl" phenylpropyl 4614 3-methylbutyl 2-methylbutyl "2-(N,N- 3- dimethylamino phenylpropyl )ethyl" 4615 cyclopropylme 3-methylbutyl "2-(N,N- 3- thyl dimethylami.no )ethyl" phenylpropyl 4616 cyclobutylmet cyclopropylme N- 3- hyl thyl dimethylamino phenylpropyl )ethyl" 4617 cyclopentylme cyclobutylmet *2-(N,N- 3- thyl hyl dimethylamino phenylpropyl )ethyl" 4616 p- cyclopentylme *2-<N,N- 3- hydroxyphenyl thyl dimethylamino phenylpropyl -methyl )ethyl" 4619 p- p- "2-(N,N- 3- nitrophenylme hydroxyphenyl dimethylamino phenylptopyl thyl -methyl )ethyl* 4620 p- p- "2-(N,N- 3- aminophenyl- nitrophenylme dimethylamino phenylpropyl methyl thyl . )ethyl" 4621 "4-{N,N- p- "2-(N,N- 3- dimethylamino aminophenyl- dimethylamino phenylpropyl )phenylmethyl m methyl )ethyl" 4622 benzyl *4-<N,N- 3-oxetanyl- "2-(N,N- dimethylamino methyl dimethyl- )phenylmethyl •a amino)ethyl" 4623 1- benzyl 3-oxetanyl- •2-{N,N- pyrolylmethyl methyl dimethyl- amino)ethyl" 4624 l-pyrazolyl- l-pyrolyl- 3-oxetanyl- "2-<N,N- nvethyl methyl methyl dimethyl-amino)ethyl" 4625 l-imidazolyl- 1- 3-oxetanyl- •2-(N,«- roethyl pyra zolylmeth methyl dimethylamino yi )ethyl" 4626 1- 1- 3-oxetanyl- "2-{N,N- indolylmethyl imlda zolylmet methyl dimethylamino hyl )ethyl" 4627 l-triazolyl- 1- 3-oxetanyl- "2-(N,N- * methyl indolylmethyl methyl dimethylamino )ethyl" 4628 1- l-triazolyl- 3-oxetanyl- "2-(N,N- - tetrazolylmet methyl methyl dimethyland.no hyl )ethyl" 200 LV 10096

Table 6 4629 2- l-tetrazolyl- 3-oxetanyl- "2-(N,N- pyridylmethyl methyl methyl dimethylarrdno )ethyl" 4630 3- 2- 3- "2-(N,N- pyridylmethyl pyridylmethyl oxetanylmethy dimethylamino 1 )ethyl" 4631 4- 3- 3- "2-(N,N- pyridylmethyl pyridylmethyl oxetanylroethy dimethylamino 1 )ethyl" 4632 cyclohexylmet 4- 3- "2-(N,N- hyl pyridylmethyl oxetanylroethy dimethylami.no , 1 )ethyl" 4633 2- cyclohexylmet 3- "2- (N,N- naphthylmethy hyl oxetanylmethy dimethylamino 1 1 )ethyl" 4634 3- 2- 3- "2-(N,N- naphthylmethy naphthylmethy oxetanylmethy dimethylamino 1 1 1 )ethyl" 4635 2- 3- 3- *2-(N,N- thiophenylmet naphthylmethy oxetanylmethy dimethylaird.no hyl 1 1 )ethyl" 4636 4-(l- 2- 3- "2-{N,N- methyl)piperi thiophenylmet oxetanylmethy dimethyland.no dinyl-methyl hyl 1 )ethyl" 4637 "(3,4* 4- (1- 3- "2-(N,N- methylenediox nvethyl)piperi oxetanylmethy dimethyland.no yphenyl)methy 1" dinyl-methyl 1 )ethyl" 4638 Λ, 2- "(3,4- 3- *2-(N,N- thienylmethyl methylenediox oxetanylnvethy dimethyland.no yphenyl)methy 1" 1 )ethyl" 4639 4- 2- 3- *2-(N,N- biphenylmethy thienylmethyl ©xetanylmethy dimethylamino 1 1 )ethyl" 4640 pyrimidinylme 4- 3- "2-(N,N- thyl biphenylmethy oxetanylmethy dimethylamino 1 1 )ethyl" 4641 2- pyrimidinylme 3- "2-(N,N- benzothiazoly thyl oxetanylmethy diroethylamirio lmethyl 1 )ethyl" 4642 2- 2- 3- · "2-(N,N- benzothiophen benzothiazoly oxetanylmethy dimethylamino ylmethyl lmethyl 1 )ethyl" 4643 2- 2- 3- *2-(N,N- thiomethyleth benzothiophen oxetanylmethy dimethylandno yi ylmethyl 1 )ethyl" 4644 2- 2- 3- "2-(N,N- thiomethylmet thiomethyleth oxetanylnvethy dimethylamino hyl yi 1 )ethyl" 4645 2- 2- 3- "2-(N,N- 4 methylpropyl thiomethylmet oxetanylmethy dimethylaiid.no hyl 1 )ethyl" 4646 2-methylbutyl 2- 3- "2-(N,N- methylpropyl oxetanylmethy dimethylamino 1 )ethyl" 201

Table 6 4647 3-methylbutyl 2-methylbutyl 3- *2-{N#N- oxetanylmethy dimethylamino 1 )ethyl" 4648 cyclopropylme 3-methylbutyl 3- 2-(N,N- thyl oxetanyln>ethy diaethylamino 4649 1 )ethyl* cyclobutylmet cyclopropylme 3- "2-{N,N- hyl thyl oxetanylmethy dimethylaaino 1 )ethyl" 4650 . cyclopentylme cyclobutylmet 3- "2-(N,N- thyl hyl oxetanylmethy dlmethylamino 1 )ethyl* 4651 p- cyclopentylme 3- "2-(N,N- hydroxyphenyl thyl oxetanylmethy dimethylamino -methyl 1 )ethyl" 4652 P* p- 3- "2-(N,N- nitrophenylme hydroxyphenyl oxetanyljnethy dimethylami.no thyl -methyl 1 )ethyl* 4653 p- p- 3- "2-(H,N- aminophenyl- nitrophenylme oxetanylmethy dimethylamino methyl thyl 1 )ethyl" 4654 "4-(N,N- p- 3- "2-(N/N- dimethylamino aminophenyl- oxetanylmethy dimethylamino )phenylmethyl M methyl 1 )ethyl" 4655 benzyl "4-(N/N- 2- 3- dimethylamino tetrahydrofur oxetanylmethy ) phenylxnethyl M anyl 1 4656 1- benzyl 2- 3- pyrolylroethyl tetrahydrofur oxetanylmethy anyl 1 4657 1- 1- 2- 3- pyrazolylmeth pyrolylmethyl tetrahydro£ur oxetanylmethy yi anyl 1 4658 1- 1* 2- 3- imidazolylmet pyrazolylmeth tetrahydrofur oxetanylmethy hyl y! anyl 1 4659 1- 1- 2- 3- indolylmethyl inddazolylmet tetrahydrofur oxetanylmethy hyl anyl 1 4660 1- 1- 2- 3- triazolylmeth indolylmethyl tetrahydrofur oxetanylmethy yi anyl 1 4661 1- 1- 2- 3- tetrazolylmet triazolylmeth tetrahydrofur oxetanylmethy hyl yi anyl 1 4662 2- 1- 2- 3- pyridylmethyl tetrazolylmet tetrahydrofur oxetanylmethy hyl anyl 1 4663 3- 2· 2- 3- · pyridylmethyl pyridylmethyl tetrahydrofur oxetanylmethy anyl 1 4664 4- 3- 2- 3- pyridylmethyl pyridylmethyl tetrahydrofur oxetanylmethy anyl 1 202 LV 10096

Table 6 4665 cyclohexylmet 4- 2- 3- hyl pyridyLnethyl tetrahydro£ur oxetanylroethy anyl 1 4666 2- cyclohexylmet 2- 3- naphthyJjnethy hyl tetrahydrofur oxetanylnethy - 1 anyl 1 4667 3- 2- 2- 3- naphthylmethy naphthylmethy tetrahydrofur oxetanylmethy 1 1 anyl 1 4668 2- 3- 2- 3- thiophenylmet naphthylmethy tetrahydrofur oxetanylmethy hyl 1 ' anyl 1 4669 4- (1- 2- 2- 3- methyl)piperi thiophenyl»et tetrahydrofur oxetanylmethy dinyl-methyl hyl anyl 1 4670 "(3,4- .4-(1- 2- 3- methylenediox methyl)piperi tetrahydrofur oxetanylmethy yphenyl)»ethy dinyl-methyl Λ m anyl 1 4671 2- "(3,4- 2- 3- thienylmethyl methylenediox tetrahydrofur oxetanylmethy yphenyl)methy 1m anyl 1 4672 4- X 2- 2- 3- biphenylmethy thienylmethyl tetrahydrofur oxetanylwethy 1 anyl 1 4673 pycimidinylme 4- 2- 3- thyl biphenylmethy tetrahydrofur oxetanylmethy 1 anyl 1 4674 2- pyrimidinylme 2- 3- benzothiazoly thyl tetrahydrofur oxetanylmethy lmethyl anyl 1 4675 2- 2- 2- 3- benzothiophen benzothiazoly tetrahydrofur oxetanyln»ethy ylmethyl lmethyl anyl 1 4676 2- 2- 2- 3- thiomethyleth benzothiophen tetrahydrofur oxetanylmethy yi ylmethyl anyl 1 4677 2- 2- 2- 3- thiomethylmet thiomethyleth tetrahydrofur oxetanylmethy hyl yi anyl 1 4678 2- 2- 2- 3- oethylpropyl thiomethylmet tetrahydrofur oxetanylmethy hyl anyl 1 4679 2-methylbutyl 2- 2- 3- methylpropyl tetrahydrefur oxetanylmethy anyl 1 4680 3-methylbutyl 2-roethylbutyl 2- 3- tetrahydrofur oxetanylmethy anyl 1 4681 cyclopropylme 3-methylbutyl 2- 3- 4 thyl tetrahydrofur oxetanylmethy anyl 1 4682 cyclobutylmet cyclopropylme 2- 3- hyl thyl tetrahydrofur oxetanylroethy anyl 1 203

Table 6 cyclopentylme cyclobutylmet 2- 3- thyl hyl tetrahydrofur oxetanylmethy anyl 1 p- cyclopentylme 2- 3- hydroxyphenyl thyl tetrahydrofur oxetanylmethy -methyl anyl 1 p- p- 2- 3- nitrophenylme hydroxyphenyl tetrahydrofur oxetanylmethy thyl -methyl anyl 1 p- p- 2* 3- aminophenyl- nitrophenylme tetrahydrofur oxetanylinethy methyl thyl anyl 1 "4-(N,N- p- 2- 3- dixnethylami.no aminophenyl- tetrahydro£ur oxetanylmethy )phenylmethyl m methyl anyl 1 benzyl "4-(NfN- 2- 2- dixnethylamino methoxypropyl tetrahydrofur )phenylxnethyl «1 anyl 1- benzyl 2- 2- pyrolylmethyl methoxypropyl tetrahydrofur anyl 1- 1- 2- 2- pyrazolylmeth pyrolylmethyl methoxypropyl tetrahydrofur yi anyl 1- 1- 2- 2- imidazolylmet pyrazolylmeth methoxypropyl tetrahydro£ur hyl yi anyl 1- 1- · 2- 2- indolylroethyl imidazolylmet methoxypropyl tetrahydrofur hyl anyl 1- 1- 2- 2- triazolylmeth indolylmethyl methoxypropyl tetrahydrofur yi anyl 1- 1- 2~ 2- tetrazolylmet trlazolylmeth methoxypropyl tetrahydrofur hyl yi anyl 2- 1- 2- 2- pyridylmethyl tetrazolylmet methoxypropyl tetrahydrofur hyl anyl 3- 2- 2- 2- pyridylxnethyl pyridylmethyl xoethoxypropyl tetrahydrofur anyl 4- 3- 2~ 2- pyridylmethyl pyridylmethyl nvethoxypropyl tetrahydrofur anyl cyclohexylmet 4· 2- 2- hyl pyridylmethyl methoxypropyl tetrahydrofur anyl 2- cyclohexylxnet 2- 2- naphthylmethy hyl methoxypropyl tetrahydrofur 1 anyl 3- 2- 2- 2- naphthylxnethy naphthylmethy methoxypropyl tetrahydrofur 1 1 anyl 204 LV 10096

Table 6 4701 2- 3- 2- 2- thiophenylmet naphthylnethy methoxypropyl tetrahydrofur hyl 1 anyl 4702 4—41— 2- 2- 2- ®ethyl)piperi thiophenylmet ©ethoxypropyl tetrahydrofur dinyl-oethyl hyl anyl 4703 "(3,4- 4-(1- 2- 2- methylenediox methyl)piperi ©ethoxypropyl tetrahydrofur yphenyl)»ethy 1" dinyl-methyl anyl 4704 2- •<3,4- 2- 2- thienylmethyl methylenediox methoxypropyl tetrahydro£ur yphenyl)methy anyl 4705 4- A 2- 2- 2- biphenylftethy thienylmethyl methoxypropyl tetrahydrofur 1 anyl 4706 pyrimidinylme 4- 2- 2- thyl biphenylmethy methoxypropyl tetrahydro£ur 1 anyl 4707 2- pyrimidinyla>6 2- 2- benzothiazoly thyl methoxypropyl tetrahydrofur lmethyl anyl 4708 2- 2- 2- 2- benzothiophen benzothiazoly methoxypropyl tetrahydrofur ylroethyl lmethyl ' 2- anyl 4709 2- 2- 2- thiomethyleth benzothiophen *aethoxypropyl tetrahydrofur yi ylmethyl anyl 4710 2- 2- 2- 2- thiomethylmet thiomethyleth methoxypropyl tetrahydrofur hyl yi anyl 4711 2- 2- 2- 2- methylpropyl thiomethylmet methoxypropyl tetrahydrofur hyl anyl 4712 2-methylbutyl 2- 2- 2- methylpropyl methoxypropyl tetrahydrofur anyl 4713 3-methylbutyl 2-methylbutyl 2- 2- methoxypropyl tetrahydrofur anyl 4714 cyclopropylme 3-methylbutyl 2- 2· thyl methoxypropyl tetrahydrofur anyl 4715 cyclobutylmet cyclopropylme 2- 2- hyl thyl methoxypropyl tetrahydrofur anyl 4716 cyclopentylme cyclobutylmet 2- 2- thyl hyl »ethoxypropyl tetrahydrofur anyl 4717 p- cyclopentylme 2- 2- hydroxyphenyl thyl jnethoxypropyl tetrahydrofur -methyl anyl 4718 p- p- 2- 2- nitrophenylme hydroxyphenyl methoxypropyl tetrahydrofur thyl -methyl anyl 205

Table 6 p- p- 2- 2- aminophenyl- nitrophenylme methoxypropyl tetrahydrofur methyl thyl anyl "4-(N,N- p- 2- 2- dimethylamino aminophenyl- xnethoxypropyl tetrahydrofur )phenylmethyl m methyl anyl benzyl "4-<N,N- 2-ethoxyethyl 2- dimethylami.no methoxypropyl )phenylroethyl m 1- benzyl 2-ethoxyethyl 2- pyrolylmethyl nvethoxypropyl 1- 1- 2-ethoxyethyl 2- pyrazolylmeth pyrolylmethyl methoxypropyl yi 1- 1- 2-ethoxyethyl 2- imidazolylmet pyrazolylmeth methoxypropyl hyl yi 1- 1- 2-ethoxyethyl 2- indolylmethyl imidazolylmet methoxypropyl hyl 1- 1- 2-ethoxyethyl 2- triazolylmeth indolylmethyl methoxypropyl yi 1- 1- 2-ethoxyethyl 2- tetrazolylmet triazolylmeth methoxypropyl hyl yi 2- 1- 2-ethoxyethyl 2- pyridylmethyl tetrazolylmet methoxypropyl hyl 3- 2- 2-ethoxyethyl 2- pyridylroethyl pyridylmethyl methoxypropyl 4- 3- 2-ethoxyethyl 2- pyridylmethyl pyridylmethyl methoxypropyl cyclohexylmet 4- 2-ethoxyethyl 2- hyl pyridylmethyl methoxypropyl 2- cyclohexylmet 2-ethoxyethyl 2- naphthylnethy ļ hyl methoxypropyl X 3- 2- 2-ethoxyethyl 2- naphthylmethy 1 naphthylmethy 1 methoxypropyl X 2- X 3- 2-ethoxyethyl 2- thiophenylmet naphthylmethy methoxypropyl hyl 1 4-(l- 2- 2-ethoxyethyl 2- methyl)piperi thiophenylmet methoxypropyl dinyl-methyl hyl "(3,4- 4-(l- 2-ethoxyethyl 2- methylenediox methyl)pipari methoxypropyl yphenyl)methy 1« dinyl-methyl X 2- "(3,4- 2-ethoxyethyl 2- thienylmethyl methylenediox methoxypropyl yphenyl)methy 1- 206 LV 10096

Table 6 4730 4- 2- 2-ethoxyethyl 2- biph«nylmethy thienylmethyl methoxypropyl 4739 X pyrimidinyln« 4- 2-ethoxyethyl 2- thyl biphenylmethy 1 methoxypropyl 4740' 2- X pyrimidinylme 2-ethoxyethyl 2- benzothiazoly thyl methoxypropyl lmethyl * 4741 2- 2- 2-ethoxyethyl 2- benzothiophen benzothiazoly inethoxypropyl ylmethyl lmethyl 4742 2- 2- 2-ethoxyethyl 2- thiomethyleth benzothiophen roethoxypropyl yi ylmethyl 4743 2- 2- 2-ethoxyethyl 2- • thiomethyljnet thiomethyleth jnethoxypropyl hyl yi 4744 2“ 2- 2-ethoxyethyl 2- methylpropyl thiomethylmet nvethoxypropyl hyl 4745 2-methylbutyl 2- 2-ethoxyethyl 2- methylpropyl methoxypropyl 4746 3-methylbutyl 2-methylbutyl 2-ethoxyethyl 2- methoxypropyl 4747 cyclopropylme 3-methylbutyl 2-ethoxyethyl 2- thyl roethoxypropyl 4748 cyclobutylmet cyclopropylme 2-ethoxyethyl 2- hyl thyl roethoxypropyl 4749 cyclopentylme cyclobutylmet 2-ethoxyethyl 2- thyl hyl roethoxypropyl 4750 p- cyclopentylme 2-ethoxyethyl 2- hydroxyphenyl thyl roethoxypropyl -methyl 4751 P* p- 2-ethoxyethyl 2- nitrophenylme hydroxyphenyl methoxypropyl thyl -methyl 4752 p- p- 2-ethoxyethyl 2- aminophenyl- nitrophenylme methoxypropyl methyl thyl 4753 "4-(N,N- p- 2-ethoxyethyl 2- dimethylamino aminophenyl- methoxypropyl ) phenylmethyl m methyl 4754 benzyl "4-<N,N- 2-U- 2-ethoxyethyl dimethylamino pyrolyl)ethyl )phenylmethyl II 4755 1- benzyl 2-U- 2-ethoxyethyl pyrolylnvethyl pyrolyl)ethyl 4756 1- 1- 2-a- 2-ethoxyethyl pyrazolylmeth pyrolylmethyl pyrolyl)ethyl yi 4757 1- 1- 2-(l- 2-ethoxyethyl imidazolylmet pyrazolylmeth pyrolyl)ethyl hyl yi 207

Table 6 4758 1- 1- 2-(1- 2-ethoxyethyl indolylroethyl imidazolylmet hyl pyrolyl)ethyl 4759 1- 1- 2-(l- 2-ethoxyethyl triazolylmeth indolylnethyl pyrolyl)ethyl yi 4760 1- 1- 2— (1— 2-ethoxyethyl tetrazolylmet trlazolylneth pyrolyl)ethyl hyl yi 4761 2- 1- 2 — {1— 2-ethoxyethyl pyridylmethyl tetrazolylmet hyl* pyrolyl)ethyl 4762 3- 2- 2-(1- 2-ethoxyethyl pyridylmethyl pyridylmethyl pyrolyl)ethyl 4763 4- 3- 2- (1- 2-ethoxyethyl pyrldylmethyl pyrldylinethyl pyrolyl)ethyl 4764 cyclohexylmet 4- 2-(1- 2-ethoxyethyl hyl' pyridylroethyl pyrolyl)ethyl 4765 2- cyclohexylmet 2-(1- 2-ethoxyethyl naphthylmethy hyl pyrolyl)ethyl 4766 X 3- 2- 2-(l- 2-ethoxyethyl naphthylmethy naphthylmethy 1 pyrolyl)ethyl 4767 X 2- X 3· 2- (1- 2-ethoxyethyl thiophenylnvet naphthylnethy pyrolyl)ethyl hyl 1 4768 4-(1- 2- 2— (1— 2-ethoxyethyl methyl)piperi thiophenyLnet pyrolyl)ethyl dinyl-methyl hyl 4769 "(3,4- methylenediox 4-(l- 2- (1- 2-ethoxyethyl methyl)piperi pyrolyl)ethyl yphenyl)methy ļ m dinyl-methyl 4770 X 2- "(3,4- 2- (1- 2-ethoxyethyl thienylmethyl methylenediox yphenyl)methy 1" pyrolyl)ethyl 4771 4- 2- 2— {1— 2-ethoxyethyl biphenylmethy thienylmethyl pyrolyl)ethyl 4772 X pyrimidinylme 4- 2 — (1— 2-ethoxyethyl thyl biphenyLnethy 1 pyrolyl)ethyl 4773 2-benzo- JL pyrimidinyl- 2- <1- 2-ethoxyethyl thiazolylmeth yi 2-benzothio- methyl pyrolyl)ethyl 4774 2-benzo- 2-(l- 2-ethoxyethyl phenylmethyl thiazolylmeth yi 2-benzothio- pyrolyl)ethyl 4775 2-thiomethyl- 2-(l- 2-ethoxyethyl ethyl phenylnethyl pyrolyl)ethyl 4776 2-thiomethyl- 2-thiomethyl- 2— (1— 2-ethoxyethyl methyl ethyl pyrolyl)ethyl 4777 2- 2-thiomethyl- 2- (1- 2-ethoxyethyl methylpropyl methyl pyrolyl)ethyl 208 LV 10096

Table 6 4778 2-methylbutyl 2- 2-(1- 2-ethoxyethyl methylpropyl pyrolyl)ethyl 4779 3-methylbutyl 2-methylbutyl 2- (1- pyrolyl)ethyl 2-ethoxyethyl 4780 cyclopropyl- 3-methylbutyl 2-{l- 2-ethoxyethyl methyl pyrolyl)ethyl 4781 ' cyclobutyl- cyclopropylme 2 — {1 — 2-ethoxyethyl methyl thyl pyrolyl)ethyl 4782 cyclopentyl- cyclobutylmet 2 — (1 — 2-ethoxyethyl methyl hyl pyrolyl)ethyl 4783 p- cyclopentylme 2-(1- 2-ethoxyethyl hydroxyphenyl -roethyl thyl _ pyrolyl)ethyl 4784 p- p- 2-{l- 2-ethoxyethyl nitrophenylme hydroxyphenyl pyrolyl)ethyl thyl -methyl 4785 P" p- 2- (1- 2-ethoxyethyl aminophenyl- nitrophenylme pyrolyl)ethyl methyl thyl 2-ethoxyethyl 4786 "4-(N,N- p- 2-(1- dimethylami.no aminophenyl- pyrolyl)ethyl )phenylmethyl methyl m 4787 benzyl 4-{N,N- 2-<l- 2- (1- dimethylamino imidazolyl)et pyrolyl)ethyl )phenylmethyl 4t hyl 4788 1- benzyl 2- Ci 2-(1- pyrolylmethyl lmi da zolyl)et hyl pyrolyl)ethyl 4789 1- 1- 2-(1- 2-41- pyra2olylmeth pyrolylmethyl imidazolyl)et pyrolyl)ethyl yi hyl 4790 1- 1- 2- (1- 2— (1— imidazolylmet pyrazolylmeth imidazolyl)et pyrolyl)ethyl hyl yi hyl 4791 1- 1- 2- (1- 2-(1- indolylmethyl imidazolylmet imidazolyl)et pyrolyl)ethyl hyl hyl 4792 1- 1- 2- (1- 2-<l- triazolylmeth indolylmethyl imldazolyl)et pyrelyl)ethyl yi hyl 4793 1- 1- 2- (1- 2 — (1— tetrazolylmet triazolylmeth imidazolyl)et pyrolyl)ethyl hyl yi hyl 4794 2- 1- 2-(1- 2-C1- pyridylmethyl tetrazolylnvet imidazolyl)et pyrolyl)ethyl hyl hyl 4795 3- 2- 2-(1- 2-(l- pyridylmethyl pyrldylmethyl imidazolyl)et hyl pyrolyl)ethyl 4796 4- 3- 2-(l- 2-U- pyridylmethyl pyridylmethyl imidazolyl)«t hyl 2-(1- pyrolyl)ethyl 4797 cyclohexylmet 4- 2-(l- hyl . pyridylwethyl imidazolyl) et pyrolyl)ethyl hyl 209

Table 6 4798 2- cyclohexylmet 2 - (1 - 2 — (1— naphthylmethy hyl imidazolyl)et pyrolyl)ethyl 1 hyl 4799 3- 2- 2 - (1 — 2-{l- naphthylmethy naphthylmethy imidazolyl)et pyrolyl)ethyl 1 1 hyl 4800 2- 3- 2— (1— 2-(1— thiophenylmet naphthylmethy inldazolyl)et pyrolyl)ethyl hyl 1 hyl 4801 4 — (1— 2- 2-(1- 2- (1- methyl)pipari thiophenylmet imidazolyl)et pyrolyl)ethyl dinyl-methyl hyl hyl 4802 "(3,4- 4-(1- 2— (I— 2-(l- nethylenedlox nethyl)piperi imldazolyl)et pyrolyl)ethyl yphenyl)methy 1" dinyl-methyl hyl 4803 X 2- •(3,4- 2- (1- 2-(1- thienylnethyl methylenediox imidazolyl)et pyrolyl)ethyl yphenyl)methy 1" hyl 4804 4- X 2- 2 - (1— 2-(1- biphenylmethy thienylmethyl imidazolyl)et pyrolyl)ethyl 1 hyl 4805 pyrinddinylme 4- 2- (1- 2 - (1— thyl bipheny2jnethy imidazolyl)et pyrolyl)ethyl 1 hyl 4806 2- pyrimidinylme 2 — (1— 2-(1- benzothiazoly thyl imidazolyl)et pyrolyl)ethyl lmethyl hyl 4807 2- 2- 2 - (1— 2-(1- benzothiophen benzothiazoly imidazolyl)et pyrolyl)ethyl ylmethyl lmethyl hyl 4808 2- 2- 2— (1 — 2-(l- thiomethyleth benzothiophen imidazolyl)et pyrolyl)ethyl yl ylmethyl hyl 4809 2- 2- 2-(1- 2-(1- thiomethylmet thiomethyleth imidazolyl)et pyrolyl)ethyl hyl yi hyl 4810 2- 2- 2-(1- 2-(l- methylpropyl thiomethylmet imidazolyl)et pyrolyl)ethyl hyl hyl 4811 2-methylbutyl 2- 2-(l- 2— (1— methylpropyl imldazolyl)et hyl pyrolyl)ethyl 4812 3-methylbutyl 2-methylbutyl 2-(1- 2—(1— imidazolyl)et hyl pyrolyl)ethyl 4813 cyclopropylzne 3-methylbutyl 2- (1- 2-(1- thyl imidazolyl)et hyl pyrolyl)ethyl 4814 cyclobutylmet cyclopropylme 2- (1- 2— (1— hyl thyl imidazolyl)et hyl pyrolyl)ethyl 4815 cyclopentylme cyclobutyln»et 2-(1- 2-(1- thyl hyl imidazolyl)et pyrolyl)«thyl hyl 4 210 LV 10096

Table 6 4816 p- cyclopentylme 2 - (1— 2 - {1 - hydroxyphenyl thyl · imidazolyl)et pyrolylJethyl -methyl hyl 4817 p- p- 2-(l- 2-{l- nitrophenylme hydroxyphenyl imidazolyl)et pyrolyl)ethyl thyl -roethyl hyl 4818 P“ p- 2- (1- 2 - (1— aminophenyl- nitrophenylme imidazolyl)et pyrolyl)ethyl tnethyl thyl hyl 4819 "4-(N,N- p- 2-(1- 2- (1— dime thylami.no aminophenyl- imidazolyl)et pyrolyl)ethyl )phenylmethyl m methyl hyl 4820 benzyl "4-(N,N- 2- 2-(1— dimethylamino pyridylmethyl imldazolyl)et )phenylmethyl m hyl 4821 1- benzyl 2- 2-{l- pyrolylmethyl pyridylmethyl imidazolyl)et hyl 4822 1- 1- 2- 2-a- pyrazolylmeth pyrolylmethyl pyridylmethyl imidazolyl)et yi hyl 4823 1- 1- 2- 2-a- iirddazolylmet pyrazolylmeth pyridylmethyl imidazolyl)et hyl yi hyl 4824 1- 1- 2- 2-(1- indolylmethyl imidazolylmet pyridylmethyl imidazolyl)et hyl hyl 4825 1- 1- 2- 2-(l- triazolylmeth indolylmethyl pyridylmethyl lmidazolyl)et yi hyl 4826 1- 1- 2- 2—{1— tetrazolylroet triazolylmeth pyridylmethyl imidazolyl)et hyl yi hyl 4827 2- 1- 2- 2-(1- pyridylmethyl tetrazolylmet pyridylmethyl imidazolyl)et hyl hyl 4828 3· 2- 2- 2*{1- pyridylmethyl pyridylmethyl pyridylmethyl imidazolyl)et hyl 4829 4' 3- 2« 2—11— pyridylmethyl pyridylmethyl pyridylmethyl imidazolyl)et hyl 4830 cyclohexylmet 4- 2- 2-(l- hyl pyridylmethyl pyridylmethyl imldazolyl)et hyl 4831 2- cyclohexylmet 2- 2—(1 — naphthylmethy hyl pyridylmethyl imidazolyl)et 1 hyl 4832 3- 2- 2- 2-(1- naphthylmethy naphthylmethy pyridylmethyl imidazolyl)et 1 1 hyl 4833 2- 3- 2- 2-(1- thiophenylmet naphthylmethy pyridylmethyl lmidazolyl)et hyl 1 hyl 211

Table 6 4834 4-(1- 2· 2- 2- (1- methyl)piperi thiophenylmet pyrldylmethyl iaidazolyl)et dinyl-methyl hyl hyl 4835 *(3,4- 4-(l- 2- 2- (1- methylenediox methyl)piperi pyridylmethyl ioidazolyl)et yphenyl)methy \ m dinyl-methyl hyl 4836 X 2- "(3,4- 2- 2-(l- thienylroethyl nethylenediox pyridylaethyl imidazolyl)et yphenyl)methy 1 m hyl 4837 4- X 2- 2- 2-(1- biphenylmethy th'ienylmethyl pyridylmethyl imidazolyl)et 1 hyl 4838 pyrimidinylme 4- 2- 2-(1- thyl biphenylmethy pyridylmethyl imidazolyl)et 1 hyl 4839 2- pyrimidinylme 2- 2-(l- benzothiazoly thyl pyridylmethyl imidazolyl)et lmethyl hyl 4840 2- 2- 2- 2- (1- benzothiophen benzothiazoly pyridyloethyl imidazolyl)et ylmethyl lmethyl hyl 4841 2- 2- 2- 2-(1- thiomethyleth benzothiophen pyridyliivethyl imidazolyl)et yi ylmethyl hyl 4842 2- 2- 2- 2-(l- thiomethylmet thiomethyleth pyridylmethyl imidazolyl)et hyl yi hyl 4843 2- 2- 2- 2-(1- methylpropyl thlomethylmet pyridylmethyl imidazolyl)et hyl hyl 4844 2-oethylbutyl 2- 2- 2-(1- *nethylpropyl pyridyloethyl imidazolyl)et hyl 4845 3-methylbutyl 2-methylbutyl 2- 2-(l- pyridylmethyl imidazolyl)et hyl 4846 cyclopropyl»e 3-nvethylbutyl 2- 2-(1- thyl pyridylaethyl imidazolyl)et hyl 2-(1- 4847 cyclobutylmet cyclopropyloe 2- hyl thyl pyridylavethyl imidazolyl) et hyl 4848 cyclopentyloe cyclobutylmet 2- 2— (1— thyl hyl pyridylmethyl laida zolyl) et hyl 4849 p- cyclopentylme 2- 2-(l- hydroxyphenyl thyl pyridylmethyl imidazolyl) et -methyl hyi * 4850 p- p- 2- 2-(1- nitrophenylme hydroxyphenyl pyridylmethyl imidazolyl)et thyl -methyl hyl 4851 p- p- 2- 2-(1- aminophenyl- nitrophenylme pyridylmethyl imidazolyl)et nethyl thyl hyl 212 LV 10096

Table 6 "4-(N,N- p- 2- 2-41- dimethylaml.no aminophenyl- pyridylroethyl imidazolyl)et )phenylmethyl m methyl hyl benzyl •4-(M/N- 2- 2- dimethylamino thiomethyleth pyridylroethyl ) phenylnvethyl m yi 1- benzyl 2- 2- pyrolylmethyl thiomethyleth pyridylmethyl yi 1- 1- . 2- 2- pyrazolylmeth pyrolylmethyl thiomethyleth pyridylmethyl yi yi 1- 1- 2- 2- imidazolylroet pyrazolylmeth thioroethyleth pyridylmethyl hyl yi yi 1- 1- 2- 2- indolylmethyl imidazolylmet thiomethyleth pyridylmethyl hyl yi 1- 1- 2- 2- triazolylmeth indolylmethyl thiomethyleth pyridylmethyl yi yi 1- 1- 2- 2- tetrazolylnet triazolylmeth thiomethyleth pyridylroethyl hyl yi yi 2- 1- 2- 2- pyridylmethyl tetrazolylmet thiomethyleth pyridylmethyl hyl yi 3- 2- 2- 2- pyridylmethyl pyridylmethyl thiomethyleth pyridylmethyl yi 4- 3- 2- 2- pyridylmethyl pyridylmethyl thiomethyleth pyridylmethyl yi cyclohexylmfet 4- 2- 2- hyl pyridylmethyl thiomethyleth pyridylmethyl yi 2- cyclohexylmet 2- 2- naphthylmethy hyl thiomethyleth pyrldyljnethyl 1 yi 3- 2- 2- 2- naphthylmethy naphthylmethy thiomethyleth pyridylmethyl 1 1 yi 2- 3- 2- 2- thiophenylmet naphthylnvethy thiomethyleth pyridylmethyl hyl 1 yi 4· (1- 2- 2- 2- methyl)piperi thiophenylmet thiomethyleth pyridylmethyl dlnyl-inethyl hyl yl "(3/4- 4-(1- 2- 2- tnethylenedioz inethyl) pipe ti thiomethyleth pyridylmethyl yphenyl)methy dinyl-methyl yi 1· 213

Table 6 2- •(3,4- 2- 2- thienylmethyl methylenedLiox thiomethyleth pyridylmethyl yphenyl)methy 1» yl 4- 2- 2- 2- biphenylmethy thienylmethyl thiomethyleth pyridylmethyl 1 yi pyrimidinylme 4- 2* 2- thyl biphenylmethy thiomethyleth pyridylmethyl 1 yi 2- pyrimidinylme 2- 2- benzothiazoly thyl thlomethyleth pyridylmethyl lmethyl • yi 2- 2- 2- 2- benzothlophen benzothiazoly thiomethyleth pyrldylmethyl ylmethyl lmethyl yi 2- 2- 2- 2“ thiomethyleth benzothiophen thiomethyleth pyridylmethyl yi ylmethyl yi 2- 2- 2- 2- thiomethylmet thioroethyleth thioroethyleth pyridylmethyl hyl yi yi 2- 2- 2- 2- methylpropyl thiomethylstet thiomethyleth pyridylmethyl hyl yi 2-roethylbutyl 2- 2- 2- methylpropyl thiomethyleth yi pyridylmethyl 3-methylbutyl 2-methylbutyl 2- 2- thiomethyleth yi pyridylmethyl cyclopropylme 3-methylbutyl 2- 2- thyl thiomethyleth yi pyridylmethyl cyclobutylmet cyclopropylme 2- 2- hyl thyl thiomethyleth yi pyridylmethyl cyclopentylme eyclobutylsvet 2- 2" thyl hyl thiomethyleth yi pyridylmethyl p- cyclopentylme 2- 2- hydroxyphenyl thyl thiomethyleth pyridylmethyl -methyl . yi p- p- 2- 2- nitrophenylme hydroxyphenyl thiomethyleth pyridylmethyl thyl -methyl yi p- p- 2- 2- arainophenyl- nitrophenylme thlomethyleth pyridylmethyl methyl thyl yi •4-{N,H- p- 2- 2- dimethylamJ.no aminophenyl- thioroethyleth pyridylmethyl )phenylmethyl methyl yi m 214 LV 10096

labie I TABLE 7

Esamplū Hambec 2L1 EJ EZ2 4886 benryl benzyl 2-methallyl 2-methallyl 4887 l-pyrolylmethyl l-pyrolylmethyl 4-inethylpentyl 4-methylpentyl 4888 1- pyrazolylmethyl 1- pyrazolylmethyl 3-methallyl 3-»ethallyl 4889 1- imidazolylmethyl 1- imidazolylmethyl 3-methylbutyl 3-methylbutyl 4890 l-indolylnethyl 1-indolylmethyl 3-»ethylpentyl . 3-methylpentyl 4891 2-pyridylnethy1 2-pyridylmethyl 3-pentyl 3-pentyl 4892 3-pyridylaethyl 3-pyridylmethyl 4-znethylpentyl 4-methylpentyl 4893 4-pyridylmethyl 4-pyridylmethyl "3< 3- dimethallyl" "3,3- dimethallyl" 4894 cyclohexyla«thyl cyclohexylmethyl "3,3- dimethylbutyl" "3,3- dijnethylbutyl" 4895 2- thiophenylmethy1 2- thiophenylmethyl allyl allyl 4896 •(3/4-methylene-dloxyphenyl)· benzyl 2-methallyl 2-roethallyl 4897 nethyl (3,4-methylene-dloxyphenyl)* cyclopropyl- inethyl 2-methallyl 4898 n>ethyl cyclobutylmethyl cyclobutylmethyl 2-®ethallyl 4899 2-thienylmethyl 2-thienylmethyl cyclopropyl- methyl cyclopropyl- iftethyl 4900 4 -biphenyloethyl 4-biphenylmethy1 iaobutyl isobutyl 4901 2- thlomethylethyl 2- thiomethylethyl n-butyl n-butyl 4 4902 p-hydroxy- phenylmetbyl p-hydroxy- phenylmethyl n-pentyl n-pentyl 4903 p- nit rophenylroethy 1 p- nitrophenylroethy 1 propyl propyl 4904 X benzyl benzyl 2-»nethallyl H 4905 l-pyrolyl»ethyl l-pyrolylmethyl 4-methylpentyl H 215 4906 1- Table 1 1- 3-methallyl H 4907 pyrazolylmethyl 1- pyrazolylmethyl 1- 3-methylbutyl H 4908 imidazolyl»ethyl 1 - indo 1 y lnve t hy 1 imidazolylmethyl l-indolylmethyl 3-methylpentyl H 4909 2-pyridylmethyl 2-pyridylmethyl 3-pentyl H 4910 3-pyridylmethyl 3-pyridylmethyl 4-iaethylpentyl H 4911 4-pyridylmethyl 4-pyridylmethyl "3,3- H 4912 cyclohexylnethyl cyclohexylmethyl dimethallyl" -3,3- H 4913 2- 2- dimethylbutyl" allyl H 4914 thiophenylmethyl *(3# 4- thiophenylmethyl 2- allyl H 4915 »ethylenedioxyph enyl)" methyl thiophenylmethy1 "(3,4-methylene- allyl H 4916 methyl dioxyphenyl)" cyclobutylmethyl H H 4917 2-thienylmethyl 2-thienylmethyl cyclopropyl- H 4918 4-biphenylmethyl 4-biphenylmethyl methyl isobutyl H 4919 2· 2- n-butyl 4920 thiomethylethyl p-hydroxyphenyl- thiomethylethyl p-hydroxyphenyl~ n-pentyl H 4921 methyl p- methyl p-nit rophenyl- propyl H 4922 nitrophenylmethy 1 benzyl methyl p-nitrophenyl- 2-methallyl 2-methallyl 4923 1-pyrolylmethy 1 methyl benzyl 4-methylpentyl 4-methylp«ntyl 4924 1- l-pyrolylmethyl 3-methallyl 3-methallyl 4925 pyrazoly lmethy1 1- 1- 3-methylbutyl 3-methylbutyl 4926 imida zolylmethyl l-indolylmethyl pyrazolylmethyl 1- 3-methylpentyl 3-methylpentyl 4927 2-pyridylmethyl imidazolylmethyl l-indolylmethyl 3-pentyl 3-pentyl 4928 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-roethylpentyl 4929 . 4-pyridylmethyl 3-pyridylmethyl "3,3- -3,3- 4930 cyclohexylmethyl 4 -pyridy lmethyl dimethallyl" "3,3- dimethallyl" 3,3- 4931 2- cyclohexylmethyl dimethylbutyl" allyl dimethylbutyl" allyl 4932 thiophenylmethyl • |3,4-methylene- cyclobexylmethyl allyl allyl 4933 dioxyphenyl)" methyl 2- cyclobutylmethyl cyclobutyl- 4934 2-thienylmethyl thiopheny!methyl " (3,4-methylene- cyc1obutylmethy1 methyl cyclobutyi- 4935 roethyl dioxyphenyl)" cyclopropyl- cycloptopyl- methyl 4936 4-biphenylmethyl methyl 2-thienylmethyl methyl isobutyl isobutyl 4937 2- 4-biphenylmethyl n-butyl n-butyl thiomethylethyl 216 LV 10096

Tableti 4938 p- hydroxyphenylmet hyl 2- thiomethylethyl n-pentyl n-pentyl 4939 p-nitrophenyl-inethyl p-hydroxy- phenylmethyl propyl propyl 4940 benzyl p-nitrophenyl-methyl 2-methallyl 2-methallyl 4941 1-pyrolylmethy1 benzyl 4-methylpentyl 4-methylpentyl 4942 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 4943 1- imidazolylmethyl 1- pyra zolylmethyl 3-methylbutyl 3-methylbutyl 4944 l-indolylmethyl 1- imida zolylnethyl 3-methylpentyl 3-methylpentyl 494S 2-pyridylmethyl 1-indolylmethyl 3-pentyl 3-pentyl 4946 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-roethylpentyl 4947 4-pyridylmethyl 3-pyridylmethyl "3# 3- dimethallyl" "3,3- dimethallyl" 4948 cyclohexylmethyl 4-pyridylmethyl "3,3- dimethylbutyl" "3,3- dimethylbutyl" 4949 2- thiophenylmethyl cyclohexylmethyl allyl allyl 4950 "(3,4-methylene-dioxyphenyl)* 4-pyridylmethyl *3,3- dimethylbutyl" "3,3- dimethylbutyl" 4951 methyl 2- thiophenylmethyl cyclobutylmethyl cyclobutyl- methyl 4952 2-thienylmethyl * (3,4-methylene-dioxy-phenyl)" cyclobutylroethyl cyclobutyl- xnethyl 4953 methyl cyclopropyl- methyl cyclopropyl- methyl isobutyl 4954 4-biphenylmethyl 2-thienylmethyl isobutyl isobutyl 4955 2- thiomethylethyl 4-biphenylmethyl n-butyl n-butyl 4956 p-hydroxy- phenyljnethyl 2- thiomethylethyl n-pentyl n-pentyl 4957 p-nitro-phenylmethyl prhydroxy- phenylmethyl propyl propyl 4958 benzyl p- nitrophenylmethy 1 2-methallyl propyl 4959 l-pyrolylwethyl <L benzyl 4-methylpentyl 2-methallyl 4960 1- pyra zolylmethyl l-pyrolylmethyl 3-methallyl 4-metbylpentyl 4961 1- imidazolylmethyl 1- pyrazolylmethyl 3-methylbutyl 3-methallyl 4962 l-indolylmethyl 1- imidazolylmethyl 3-methylpentyl 3-methylbutyl 4963 2-pyridylmethyl l-indolylmethyl 3-pentyl 3-methylpentyl 4964 3-pyridylmethyl 2-pyridylxnethyl 4-methylpentyl 3-pentyl 4965 4-pyridylmethyl 3-pyridylmethyl "3,3- dimethallyl" 4-methylpfntyl 4966 cyclohexylmethyl 4-pyridylmethyl "3,3- dimethylbutyl" "3,3- diinethallyl" 4967 2- thlophenylmethyl cyclohexylmethyl allyl "3,3- diinethylbutyl" 4968 " <3, 4-methylene-dioxyphenyl)" cyclohexylmethyl allyl "3,3- dimethylbutyl" 217 labie.-? 4969 methyl 2- thiophenylmethyl cyclobutylmethyl allyl 4970 2-thienyl»ethy1 •(3,4-methylene-dioxyphenyl)" cyclobutylmethyl allyl 4971 ®ethyl cyc1opropylmethy 1 cyclobutyljnethyl allyl 4972 .4-biphenylroethyl 4 2-thienylmethyl isobutyl. cyclopropyl- inethyl iaobutyl 4973 2- thionethylethyl 4-biphenylmethyl n-butyl 4974 p-hydroxyphenyl- methyl 2- thiomethylethyl n-pentyl n-butyl 4975 p-nitcophenyl- wethyl p-hydroxyphenyl- methyl propyl n-pentyl 4975A benzyl benzyl cyclopropyl- methyl N,K-diroethyl- aminoethyl 218 LV 10096 labie 8

TABLK 8 S N I k/R” \ Γ HO E-g&mple flmūbet &1 E1 L22 m 4976 benzyl ben*yl 2-®ethallyl 2-methallyl 4977 l-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 4 -nvethylpentyl 4978 1- 1- 3-methallyl 3-methallyl pyrazolylmethyl pyrazolylmethyl 3-aethylbutyl 4979 l-imidazolyl- l-imidazolyl- 3-methylbutyl inethyl methyl 4980 1 -indolyljnethyl 1-indolylmethyl 3-methylpentyl 3-oethylpentyl 4981 2-pyridylmethyl 2-pyridylmethyl 3-pentyl 3-pentyl 4982 3-pyridylmethyl 3~pyridylmethyl 4-methylpentyl 4-methylpentyl 4983 4-pyridylmethyl 4 *pyridylmethyl "3,3- •3,3- • diroethallyl· dimethallyl" 4984 cyclohexyl- cyclohexylmethy "3,3- "3,3- methyl 1 dlmethylbutyl" dimethylbutyl" 4985 2-thiophenyl- 2- allyl allyl methyl thiophenylmethy 1 4986 "(3,4- "(3,4- cyclobutyl- cyclobutyl- roethylene- methylene- methyl methyl dioxy-phenyl)- dioxyphenyl)- methyl" methyl* 4987 2-thienyl®ethyl 2-thienylmethyl cyclopropyl- cyclopropyl- methyl nethyl 4988 4- 4- lsobutyl isobutyl biphenylmethyl blphenylmethyl « 4989 2- 2- n-butyl n-butyl 4990 thiomethylethyl thiomethylethyl p-hydroxy- p-hydroxy- n-pentyl n-pentyl 4991 phenylmethyl phenyl-methyl p-'nitrophenyl- p-nitrophenyl- propyl propyl inethyl methyl 219 lablfi-fi 4992 benzyl benzyl 2-methallyl H 4993 1-pyrolylmethyl l-pyrolylnethyl 4-methylpentyl H 4994 1- 1- 3-methallyl H pyra zolylmethyl pyra zolylnethyl 4995 l-imidazolyl- l-imidazolyl- 3-methylbutyl H nethyl nethyl 4996 l-indolylmethyl l-indolylmethyl 3-methylpentyl H 4997 2-pyridylmethy1 2-pyridylroethyl 3-pentyl H 4998 3-pyridylmethyl 3-pyridyljnethyl 4-nethylpentyl H 4999 4-pyridylroethyl 4-pyridylmethyl "3 3- dL^ethallyl" H 5000 cyclohexyl- cyclohexyl- "3,3- H methyl methyl dimethylbutyl" 5001 2-thiophenyl- 2-thiophenyl- allyl H methyl n»ethyl 5002 "0,4- methylenedioxy- "0,4- methylenedioxy- cyclobutyl- methyl H phenyl)methyl" phenyl)methyl" 5003 2-thienyljnethyl 2-thienylznethyl cyclopropyl- methyl H 5004 4- 4- lsobutyl H biphenylmethyl biphenylmethyl 5005 2- 2- n-butyl thiomethylethyl thiomethylethyl 5006 p- p- n-pentyl H hydroxyphenyl- hydroxyphenyl- methyl methyļ 5007 p-nitrophenyl- p-nitrophenyl- propyl H xnethyl methyl 5008 benzyl p-nitrophenyl- methyl 2-methallyl 2-methallyl 5009 l-pyrolylinethyl benzyl 4-methylpentyl 4-roethylpentyl 5010 1- l-pyrolylnvethyl 3-methallyl 3-methallyl pyrazolylmethyl 5011 l-imidazolyl- 1- 3-methylbutyl 3-jnethylbutyl methyl pyrazolylmethyl 5012 l-indolylmethyl 1- 3-inethylpentyl 3-methylpentyl imidazolylmethy 1 5013 2-pyridylmethyl X l-indolyl»ethyl 3-pentyl 3-pentyl 5014 3-pyridylmethyl 2-pyridylmethy1 4-methylpentyl 4-methylpentyl 5015 4-pyridylmethyl 3-pyridylmethyl "3,3- "3,3- dinethallyl" dimethallyl" 5016 cyclohexylmethy 4-pyridylmethyl "3,3- "3,3- 1 diroethylbutyl" dimethylbutyl" 5017 2-thiophenyl- cyclohexyl- allyl allyl methyl methyl 5018 "0,4- 2-thiophenyl- cyclobutylmethy cyclobutylmethy methylenedioxy- methyl 1 1 phenyl)methyl" • 5019 2-thienylmethyl "0,4- cyclopropylmeth cyclopropylmeth methylenedioxyp henyl)methyl" yi yi 5020 4- biphenylmethyl 2-thienyLnethyl isobutyl isobutyl 5021 2- 4- n-butyl n-butyl thiomethylethyl biphenylmethyl 220 LV 10096

Tablg 8 5022 p- hydroxyphenyl- inethyl 2- thiomethylethyl n-pentyl »' n-pentyl 5023 p-nitrophenyl- nethyl p- hydroxyphenyl- »ethyl propyl propyl 5024 - benzyl p-aitrophenyl- »ethyl 2-methallyl 2-inethallyl 5025 l-pyrolylmethyl benzyl 4-roethylpentyl 4-methylpentyl 5026 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-jnethallyl 5027 l-imidazolyl- methyl 1- pyra zol'ylroethyl 3-methylbutyl 3-methylbutyl 5028 - l-indolylmethyl l-imidazolyl- methyl 3-nvethylpentyl 3-methylpentyl 5029 2-pyridylmethyl l-indolylmethyl 3-pentyl 3-pentyl 5030 3-pyridylmethy1 2-pyridylxnethyl 4-methylpentyl 4-methylpentyl 5031 4-pyridylmethyl 3-pyridylmethyl "3,3- dimethallyl* "3,3- dimethallyl* 5032 cyclohexylroethy 1 4-pyridylmethyl "3,3- dimethylbutyl* "3,3- diroethylbutyl" 5033 2-thiophenyl- methyl cyclohexylmethy 1 allyl allyl 5034 "(3,4- 2- cyclobutylmethy cyclobutylmethy methylenedioxyp henyl)methyl* thiophenylmethy 1 1 1 5035 2-thienylmethyl "(3,4- methylenedioxyp henyl)methyl" cyclopropyl- xnethyl cyclopropyl- nethyl 5036 4- biphenylmethyl 2-thienyljnethyl isobutyl isobutyl 5037 2- thiomethylethyl 4- biphenylmethyl n-butyl n-butyl 5038 P- hydroxyphenyl- methyl 2- thiemethylethyl n-pentyl n-pentyl 5039 p-nitrophenyl- methyl P* hydroxyphenylme thyl propyl propyl 5040 benzyl p-nitrophenyl- methyl 2-methallyl propyl 5041 l-pyrolylmethyl benzyl 4-methylpentyl 2-sethallyl 5042 1· pyrazolylmethyl l-pyrolylmethyl 3-»ethallyl 4-methylpentyl 5043 l-imidazolyl- nvethyl 1- pyrazolylmethyl 3-methylbutyl 3-methallyl 5044 1-indoly lroethy1 l-imidazolyl- methyl 3-methylpentyl 3-»ethylbutyl 5045 2-pyridylmethyl l-indolylmethyl 3-pentyl 3-methylpentyl 5046 3-pyridylraethyl 2-pyrldylmethyl 4-methylpentyl 3-pentyl « 5047 4-pyridylfflethyl 3-pyridylmethyl *3,3- diinethallyl* 4-wethylpentyl 5048 cyclohexylmethy 1 4-pyridylmethyl "3,3- dimethylbutyl" i>3 3- dimethallyl" 5049 2-thiophenyl- methyl cyclohexyl- methyl allyl "3,3- dimethylbutyl" 221Iable„fl 5050 "(3,4- methylenedioxyp 2- thiophenylmethy cyclobutyl- methyl *llyl henyl)methyl" 1 ,· 5051 2-thienyl»ethyl "(3,4- nethylenedioxyp henyl)methyl" cyclopropyl- methyl cyclobutylmethy 1 5052 4- biphenyl®ethyl 2-thieny lmethyl lsobutyl cyclopropyl- methyl 5053 2- thiomethylethyl 4- biphenylroethyl n-butyl isobutyl 5054 P* hydroxyphenyl- methyl 2- thic>methylethyl n-pentyl n-butyl 5055 p-nitrophenyl- methyl p- hydroxyphenyl- inethyl propyl n-pentyl (.·,

C « 222 LV 10096

Table 9 TABLE 9 S

M.uahfijc &4 E2 Eli Eli 5056 benzyl benzyl 2-methallyl 2-nvethallyl 5057 l-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 4-wethylpentyl 5058 5059 1- pyra zolylmethyl 1- pyrazolylxnethyl 3-methallyl 3-methallyl 1- imidazolylmethy 1 1- inida zolylnethy 1 3-methylbutyl 3-methylbutyl 5060 JL l-indolylmethyl X 1-indolylmethy1 3-methylpentyl 3-methylpentyl 5061 2-pyridylmethyl 2-pyridylmethyl 3-pentyl 3-pentyl 5062 3-pyr idylmethy1 3-pyridylmethyl 4-methylpentyl 4-methylpentyl 5063 4-pyridy lmethy1 4-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5064 cyclohexylmethy cyclohexylmethy 3,3- 3,3- 5065 1 1 dimethylbutyl diiftethylbutyl 2- thiophenylmethy 1 2- thiophenylmethy j allyl allyl 5066 (3,4- (3,4- cyclobutylmethy cyclobutyl«iethy methylenedioxyp henyl)methyl methylenedioxyp henyl)methyl 1 1 5067 2-thienylmethyl 2-thienylmethyl cyclopropylmeth yi cyclopropylmeth 5068 4- biphenylmethyl 4- biphenylmethyl isobutyl isobutyl « 5069 2- thiomethylethyl 2- thiomethylethyl n-butyl n-butyl 5070 p- hydroxyphenylme thyl p- hydroxyphenylme thyl n-pentyl n-pentyl 223

Table 9 5071 ρ- p- propyl propyl nitrophenylmeth nitrophenylmeth yi yi 5072 benzyl benzyl 2-methallyl H 5073 l-pyrolylmethyl l-pyrolylmethyl 4-methylpanty1 M 5074 1- 1- 3-methallyl H - pyrazolylmethyl pyrazolylmethyl 5075 1- 1- 3-methylbutyl H imidazolylmethy 1 imidazolylmethy 1 5076 l-indolylmethyl l-indolylmethyl 3-methylpentyl H 5077 2 -pyridylroethyl 2-pyridylmethyl 3-pentyl H 5078 3-pyridylmethyl 3-pyridy lmethy1 4-methylpentyl H 5079 4-pyridylmethyl 4-pyridylroethyl 3,3-dimethallyl H 5080 cyclohexylmethy cyclohexylmethy 3,3- H 1 1 dimethylbutyl 5081 2- 2- allyl H thiophenylroethy 1 thiophenylmethy 1 5082 (3,4- (3,4- cyclobutylmethy H methylenedioxyp methylenedioxyp 1 henyl)methyl henyl)methyl 5083 2-thienylmethyl 2-thienylmethyl cyclopropylmeth yi iaobutyl H 5084 4· 4- H biphenylmethyl biphenylmethyl 5085 2- 2- n-butyl thiomethylethyl thiomethylethyl 5086 p- p- n-pentyl H hydroxyphenylme hydroxyphenylxne thyl thyl 5087 p- p- propyl H nit rophenylmeth nitrophenylmeth yi yi 5088 benzyl p- nitrophenylmeth y! benzyl 2-methallyl 2-roethallyl 5089 1 -py rolylmethyl 4-methylpentyl 4-methylpentyl 5090 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 5091 1- 1- 3-methylbutyl 3-methylbutyl imida zoly lmethy 1 pyrazolylmethyl 5092 l-indolylmethyl 1- 3-methylpentyl 3-methylpentyl imida zolylmethy 1 5093 2-pyridylmethy1 X l-indolylmethyl 3-pentyl 3-pentyl 5094 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-methylpentyl 5095 4 -py ridylmethyl 3-pyridylmethyl 3,3-dimethallyl 3,3-dimetHallyl 5096 cyclohexylmethy 4-pyridylmethyl 3,3- 3,3- 1 dimethylbutyl dimethylbutyl 5097 2- cyclohexylmethy allyl allyl thiophenylmethy 1 1 • 224 LV 10096

Table 9 5098 <3,4- 2- cyclobutylmethy cyclobutylmethy methylenedioxyp henyl)methyl thiophenylmethy 1 1 1 5099 2-thienylroethyl <3,4- methylenedioxyp henyl)methyl cyclopropyImeth yi cyclopropyImeth yi 5100 4- biphenylmethyl 2-thienylmethyl isobutyl isobutyl 5101 2- thiomethylethyl 4- biphenylmethyl n-butyl n-butyl 5102 P- hydroxyphenylme thyl 2- thiomethylethyl n-pentyl n-pentyl 5103 p- nit ropheny Imeth yi p- hydroxyphenylme thyl propyl propyl 5104 benzyl p- nitrophenyImeth yi benzyl 2-methallyl 2-methallyl 5105 1 -pyrolylmethy1 4-methylpentyl 4-methylpentyl 5106 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 5107 1- imida z o ly lme t hy 1- pyrazolylmethyl 3-methylbutyl 3-methylbutyl 5108 i l-indolylmethyl 1- imidazolylmethy 1 3-methylpentyl 3-methylpentyl 5109 2~pyridylmethyl X 1-indolylroethyl 3-pentyl 3-pentyl 5110 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-methylpentyl 5111 4 -py r idylmethy 1 3-pyridylmethyl 3,3-diroethallyl 3,3-dimethallyl 5112 cyclohexylmethy 1 4-pyridylroethyl 3,3- dimethylbutyl 3,3- dimethylbutyl 5113 2- thiophenylmethy 1 cyclohexylmethy 1 allyl allyl 5114 Λ <3,4- 2- cyclobutylmethy cyclobutylmethy methylenedioxyp henyl)roethyl thiophenylmethy 1 1 1 5115 2-thienylmethyl <3,4- methylenedioxyp henyl)methyl cyclopropyImeth yi cyclopropylmeth yi 5116 4- biphenylmethyl 2-thienylmethyl isobutyl isobutyl 5117 2- thiomethylethyl 4- biphenylmethyl n-butyl n-butyl 5118 p- hydroxyphenylme thyl 2- thiomethylethyl n-pentyl n-pentyl 5119 p- nitrophenyImeth yi p- hydroxyphenylme thyl propyl propyl f 5120 benzyl P" nit rophenyImeth yi benzyl 2-methallyl propyl 5121 l-pyrolylmethyl 4-methylpentyl 2-roethallyl 225labie 9 5122 1- l-pyrolylmethyl 3-roethallyl 4-methylpentyl pyra zolylnethyl • 5123 1- 1- 3-methylbutyl 3-methallyl imida zolylmethy 1 pyrazolylmethyl 5124 X l-indolylinethyl 1- 3-methylpentyl 3-methylbutyl imidazolylmethy Λ 5125 2-pyridylmethyl X l-indolylmethyl 3-pentyl 3-nethylpentyl 5126 3-pyridylmethyl 2-pyridylmethyl 4-xnethylpentyl 3-pentyl 5127 4-pyridylmethyl 3-pyridylmethyl 3,3-dimethallyl 4-methylpentyl 5128 cyclohexylmethy 4-pyridylmethy1 3,3- 3,3-dinvethallyl 1 dimethylbutyl 5129 2- cyclohexylmethy allyl 3,3- thiophenylaethy ļ 1 dlnethylbutyl 5130 <3,4- 2- cyclobutylmethy allyl methylenedioxyp thiophenylnvethy 1 henyl)methyl 1 5131 2-thienylmethyl <3,4- cyclopropylmeth cyclobutylmethy methylenedioxyp yi 1 henyl)methyl 5132 4- 2-thienylmethyl isobutyl cyclopropylmeth biphenylmethyl yi 5133 2- 4- n-butyl isobutyl thiomethylethyl biphenylmethyl 5134 p- 2- n-pentyl n-butyl hydroxyphenylme thiomethylethyl thyl 5135 p- p- propyl n-pentyl nitrophenylnveth hydroxyphenylme yi thyl 226LV 10096

Table 10 TABLE 10 R\ A R!a

hT

ILK&mplft Ei. El Eli Hambftg 5136 benzyl benzyl 2-methallyl 2-nvethallyl 5137 1-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 4-methylpentyl 5138 1- 1- 3-methallyl 3-methallyl pyrazolylmethyl pyrazolylroethyl 5139 l-imidazolyl- l-imidazolyl- 3-methylbutyl 3-roethylbutyl methyl roethyl 5140 l-indolylmethyl l-indolyLnethyl 3-methylpentyl 3-methylpentyl 5141 2-pyr idylroethyl 2-pyridylmethyl 3-pentyl 3-pentyl 5142 3 -pyridylmethy1 3-pyridylmethyl 4-methylpentyl 4-methylpentyl 5143 4-pyridylmethyl 4-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5144 cyclohexyl- cyclohexyl- 3,3- 3,3- methyl methyl diroethylbutyl diinethylbutyl 5145 2-thiophenyl- 2-thiophenyl- allyl allyl methyl methyl 5146 (3,4- (3,4-methylene- cyclobutylmethy cyclobutylmethy methylenedioxyp dioxyphenyl)met 1 1 henyl)methyl hyl 5147 2-thienyl®ethyl 2-thienylmethyl cyclopropylmeth cyclopropylmeth yi yi 5148 4- 4-biphenyl- isobutyl isobutyl biphenylmethyl methyl 5149 2- 2-thiomethyl- n-butyl n-butyl thiomethylethyl ethyl 5150 p-hydroxy- p-hydroxy- n-pentyl n-pentyl phenyl-methyl phenyl-methyl & 5151 p-nitrophenyl- p-nitrophenyl- propyl propyl methyl methyl 5152 benzyl benzyl 2-methallyl R 5153 l-pyrolylroethyl 1 -py rolylnvethyl 4-methylpenty1 H 51S4 1- 1- 3-methallyl H pyrazolylmethyl pyrazolylmethyl 227 515$ l-imidazolyl- labie lfl l-iirddazolyl- 3-»ethylbutyl H 5156 methyl l-indolylmethyl methyl 1-indolylmethy1 3-methylpeņtyl H 5157 2-pyridyl®ethyl 2-py r idy liaethy 1 3-pentyl H ' 5158 3 -py r idylroethy 1 3-pyridylaethyl 4-methylpentyl H 5159 4-pyridylmethyl 4-py r idy line thy 1 3,3-diwethallyl H 5160 ' cyclohexyl- cyclohexyl- 3,3- H 5161 methyl 2-thiophenyl- inethyl 2-thlophenyl- dimethylbutyl allyl H 5162 methyl (3,4-methylene- methyl (3,4-methylene- cyclobutyl- H 5163 dloxyphenyl) -m«thyl 2-thienylmethyl ioxyphenyl)- methyl 2-thienylmethyl methyl cyclopropyl- H 5164 4- 4- tnethyl isobutyl H 5165 biphenylmethyl 2- biphenylmethyl 2- n-butyl 5166 thiomethylethyl p- thiomethylethyl p- n-pentyl H 5167 hydroxyphenyl- methyl p-nitrophenyl- hydroxyphenyl- methyl p-nitrophenyl- propyl H 5168 methyl benzyl iftethyl p-nltrophenyl- 2-methallyl 2-methallyl 5169 1-pyrolyl»ethyl nethyl benzyl 4-methylpentyl 4-methylpentyl 5170 1- l-pyrolyl- 3-methallyl 3-methallyl 5171 pyrazolylmethyl 1- methyl l-pyrazolyl- 3-methylbutyl 3-roethylbutyl 5172 imidazolylmethy 1 l-indolylmethyl methyl l-imidazolyl- 3-methylpentyl 3-methylpentyl 5173 2-pyridylmethyl methyl l-indolylmethyl 3-pentyl 3-pentyl 5174 3-pyridylmethyl 2-pyridylroethyl 4-methylpentyl 4-methylpentyl 5175 4 -pyr idybnethyl 3-pyridylaethyl 3,3-dimethallyl 3,3-diraethallyl 5176 cyclohexyl- 4-pyridylmethyl 3,3- 3,3- 5177 methyl 2-thiophenyl- cyclohexyl- dimethylbutyl allyl dimethylbutyl allyl 5178 methyl (3/ 4- roethyl 2-thiophenyl- cyclobutyl®ethy cyclobutylmethy methylenedioxyp methyl 1 1 5179 henyl)methyl 2-thienyloethyl (3,4- cyclopropylmeth cyclopropy lmeth 5180 4- methylenedioxyp henyl)methyl 2-thienylmethyl yi iaobutyl yi isobutyl 5181 biphenylmethyl 2- 4- n-butyl n-butyl * 5182 thioroethylethyl p- biphenylmethyl 2— n-pentyl ii-pentyl hydroxyphenyl- methyl thiomethylethyl 226 LV 10096

labie. 1Q 5183 p-nitrophenyl- nethyl p- hydroxyphenyl- wethyl propyl propyl 51B4 benzyl p-nitrophenyl- methyl 2-nvethallyl 2-methallyl 5185 l-pyrolylmethyl benzyl 4-methylpentyl 4-methylpentyl 5186 • 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 5187 l-imidazolyl- methyl 1- pyrazolylmethyl 3-methylbutyl 3-roethylbutyl 5188 l-indolylmethyl 1- imidazoļylmethy 1 3-methylpentyl 3-methylpentyl 5189 2-pyridyImethyl X 1-indolylmethyl 3-pentyl 3-pentyl 5190 3-pyridylroethyl 2-pyridyl»ethyl 4-nvethylpentyl 4-methylpentyl 5191 4-pyridylmethyl 3-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5192 cyclohexyl- methyl 4-pyridylitvethyl 3,3- dimethylbutyl 3,3- dimethylbutyl 5193 2-thiophenyl- methyl cyclohexyl- methyl allyl- allyl 5194 (3,4- methylenedioxy- phenyl)methyl 2-thiophenyl- methyl cyclobutylmethy 1 cyclobutyl- methyl 5195 2-thienylwethyl (3,4- methylenedioxy- phenyl)methyl cyclopropyl- n\ethyl cyclopropyl- methyl 5196 4- biphenyljt>ethyl 2-thienylmethyl iaobutyl lsobutyl 5197 2- thiomethylethyl 4- biphenylmethyl n-butyl n-butyl 5198 p- hydroxyphenyl- methyl 2- thiomethylethyl n-pentyl n-pentyl 5199 p-nitrophenyl- nethyl p- hydroxyphenyl- jnethyl propyl propyl 5200 benzyl p-nit rophenyl-methyl 2-methallyl propyl 5201 l-pyrolylmethyl benzyl 4-methylpentyl 2-methallyl 5202 1- pyrazolylmethyl l-pyrolylmethyl 3-roethallyl 4-methylpentyl 5203 l-imidazolyl- methyl 1- pyrazoly!methyl 3-methylbutyl 3-inethallyl 5204 l-indolylmethyl l-imidazolyl- roethyl 3-methylpentyl 3-methylbutyl 5205 2-pyridylmethyl 1-indolylmethyl 3-pentyl 3-methylpentyl 5206 3 -py r idy lmethy 1 2-pyridylroethyl 4-methylpentyl 3-pentyl 5207 4-pyridylmethyl 3 -py r idy linethy 1 3,3-dimethallyl 4-methylpentyl 5208 cyclohexyl- methyl 4-pyridylmethyl 3,3- dimethylbutyl 3,3-dimetliallyl 5209 2-thiophenyl- roethyl cyclohexyl- methyl allyl 3,3- dimethylbutyl 5210 (3,4- methylenedioxyp henyl)methyl 2-thlophenyl- methyl cyclobutylroethy 1 allyl 229 labie ,1Q„ 5211 2-thienylmethyl <3,4- methylenedioxy- phenyl)methyl cyclopropylmeth n i cyclobutyl»ethy 1 5212 4- biphenylmethyl 2-thienylmethyl isobutyl cyclopropyl- nethyl 5213 2- thiomethylethyl 4- blphenylmethyl n-butyl isobutyl 5214 p- hydroxyphenyl- methyl 2- thiomethylethyl n-pentyl n-butyl 5215 p-nitrophenyl- methyl p- hydroxyphenyl- methyl propyl n-pentyl

B « ' 230 LV 10096

Table 11 7abi· 11

Exampl· Kmabez ΈΛ E2 m B21 5216 benzyl benzyl 2-methallyl 2-methallyl 5217 l-pyrolylaethyl l-pyrolyln»thyl 4-a»thylpentyl 4-a»thylpentyl 5218 1- pyrazolylmethyl 1- pyrazolyla»thyl 3-o»thallyl 3-nethallyl 5219 1- iaddazolyla»thy 1 1- inddazolylmethy 1 3-xr»tbylbutyl 3-nethylbutyl 5220 l-indolylmethyl l-indolylroethyl 3-methylpentyl 3-a»thylpentyl 5221 2-pyridyln»thyl 2-pyridylmethyl 3-pentyl 3-pentyl 5222 3-pyridyla»thyl 3-pyridyla»thyl 4-n»tbylpentyl 4-oethylpentyl 5223 4-pyridylmethyl 4-pyridylmethyl 3;3-dimethallyl 3,3-dimethallyl 5224 cyclohexyl- n»thyl cyclohexyl- methyl 3,3- dimetbylbutyl 3,3- din»tbylbutyl 5225 2-thiophenyl- methyl 2-thiophenyl- methyl allyl allyl 5226 (3,4-methylene-dioxyphenyl)-nethyl (3,4-methylene-dioxyphenyl)-methyl cyclobutyloethy 1 cyclobutyl- inethyl 5227 2-thienylnethyl 2-thienylmethyl cyclopropyl- methyl cyclopropylmeth yi 5228 4- blphenyla»thyl 4- biphenylmethyl isobutyl isobutyl 5229 2- thion»thylethyl 2- thiomethylethyl n-butyl n-butyl 5230 p- hydroxyphenyl- methyl p- hydroxyphenyl- methyl n-pentyl n-pentyl 5231 p-nitrophenyl- roethyl p-nit rophenyl-methyl propyl ptopyl » · 5232 benzyl benzyl 2-methallyl H 5233 1-py rolyln»thyl 1-pyrolyla»thyl 4 -methylpentyl H 5234 1- pyra zolylroethyl l-pyrazolyl- methyl 3-roetballyl U 5235 1-laidazolyl-metbyl l-imidazolyl- methyl 3-methylbutyl. B 231JableUl 5236 l-indolylmethyl l-indolyl»ethyl 3-methylpentyl H 5237 2-pyridylmethyl 2-pyridyl»ethy1 3-pentyl H 5238 3 -py r idy laethy 1 3-pyridylmethyl 4-methylpentyl H 5239 4 -py ridylmethyl 4-pyridy lmethy1 3,3-diaethallyl H 5240 _ cyclohexyl- cyclohexyl- 3,3- H methyl methyl dimethylbutyl 5241 2-thiophenyl- 2-thiophenyl- allyl H methyl »ethyl 5242 (3,4-jnethylene- (3,4-aethylene- cyclobutyl- K dioxyphenyl) - dioxyphenyl)- methyl nvethyl nethyl 5243 2-thienylmethyl 2-thienylmethy1 cycloptopyl- nvethyl H 5244 4- 4- isobutyl H biphenylmethyl biphenylmethyl 5245 2- 2- n-butyl thiomethylethyl thiomethylethyl 5246 p- P" n-pentyl H hydroxyphenyl- hydroxyphenyl» nethyl aethyl 5247 p-nitrophenyl- p-nitrophenyl- propyl H nvethyl methyl 5248 benzyl p-nitrophenyl- methyl 2-methallyl 2-aethallyl 5249 l-pyrolylmethyl benzyl 4-methylpentyl 4-aethylpentyl 5250 1- pyrazolylroethyl l-pyrolylaethyl 3-methallyl 3-aethallyl 5251 l-imidazolyl- 1- 3-n>ethylbutyl 3-methylbutyl aethyl pyrazolylmethyl 5252 l-indolylroethyl l-imidazolyl- tnethyl 3-methylpentyl 3-aethylpentyl 5253 2-pyridylaethyl l-indolylmethyl 3-pentyl 3-p«ntyl 5254 3-pyridylnethyl 2-pyridylmethyl 4-methylpentyl 4-aethylpentyl 5255 4-pyridylmethyl 3-pyridylaethyl 3,3-dimethallyl 3,3-diaethallyl 5256 cyclohexyl- 4-pyridylaethy1 3,3- 3/3- methyl diaethylbutyl diaethylbutyl 5257 2-thiophenyl- cyclohexyl- allyl allyl methyl methyl 5258 <3,4- 2-thiophenyl- cyclobutyl- cyclobutyl- methylenedioxy- phenyl)methyl oethyl methyl aethyl cyclopropyl- 5259 2-thienylaethyl (3,4-methylene- cyclopropyl- dioxyphenyl)-jnethyl methyl aethyl 5260 4- biphenylmethyl 2-thienylaethyl iaobutyl isobutyl 5261 2- 4- n-butyl n-butyl thlomethylethyl biphenylaethyl 5262 p- 2- n-pentyl n-pentyl : hydroxyphenyl- methyl thiomethylethyl 5263 p-nitrophenyl- p- propyl propyl methyl hydroxyphenyl- methyl 2-aethallyl 5264 benzyl p-nit rophenyl- 2-methallyl methyl 232 Table-11 LV 10096 5265 l-pyrolyl»ethyl benzyl 4-methylpentyl 4-xnethylpentyl 5266 1- pyrazolybnethyl l-pyrolylmethyl 3-roethallyl 3-methallyl 5267 l-imidazolyl- methyl 1- pyrazolylmethyl 3-methylbutyl 3~methylbutyl 5268 1-indolylmethyl 1- imlda zolylmethy 1 3-methylpentyl 3-methylpentyl 5269 2-pyridylnethy1 l-indolylmethyl 3-pentyl 3-pentyl 5270 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-methylpentyl 5271 4-pyridyl»ethyl 3-pyridylmethyl 3,3-diavethallyl 3,3-diinethallyl 5272 cyclohexyl- methyl 4-pyridylroethyl 3,3- dimethylbutyl 3,3- dimethylbutyl 5273 2-thiophenyl- »ethyl cyclohexy- lmethyl allyl ailyi. 5274 (3,4- 2-thiophenyl- cyclobutyl- cyclobutyl- methylenedioxyp henyl)methyl methyl methyl methyl 5275 2-thienylmethyl <3,4- methylenedioxyp henyl)methyl cyclopropyl- methyl cyclopropyl- methyl 5276 4- biphenylroethyl 2-thienylmethyl iaobutyl isobutyl 5277 2- thioroethylethyl 4- biphenylmethyl n-butyl n-butyl 5278 p- hydroxyphenyl- methyl 2 - thiomethylethyl n-pentyl n-pentyl 5279 p-nitrophenyl- methyl p- hydroxyphenyl- »ethyl propyl propyl 5280 benzyl p-nitrophenyl- methyl 2-methallyl propyl 5281 l-pyrolylmethyl benzyl 4-wethylpentyl 2-methallyl 5282 1- pyrazolylmethyl 1-pyrolylmethyl 3-methallyl 4-methylpentyl 5283 1- imidazolylnethy 1 1- pyrazolylmethyl 3-methylbutyl 3-methallyl 5284 JL l-lndolylmethyl l-imidazolyl- methyl 3-methylpentyl 3-roethylbutyl 5285 2-pyridylmethyl l-indolylmethyl 3-pentyl 3-methylpentyl 5286 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 3-pentyl 5287 4-pyridylmethyl 3-pyridylnvethyl 3,3-dimethallyl 4-methylpentyl 5288 cyclohexyl- xnethyl 4-pyridylmethyl 3,3- dimethylbutyl 3,3-dlroethallyl 5289 2-thiophenyl- cyclohexyl- allyl 3,3- roethyl methyl dimethylbutyl 5290 (3,4- 2-thiophenyl- cyclobutylnvethy allyl n>ethylenedioxy- phenyl)methyl methyl 1 cyclobutyl- methyl 5291 2-thienylmethyl (3,4- methylenedioxy- phenyl)jnethyl cyclopropyl- methyl 5292 4- biphenylroethyl 2-thienylmethyl isobutyl cyclopropyl- roethyl 233 5293 2- Table 11 4- n-butyl isobutyl 5294 thiomethylethyl ρ- biphenylmethyl 2- n-pentyl n-butyl 5295 hydroxyphenyl- nvethyl p-nitrophenyl- thiomethylethyl p— propyl n-pentyl nethyl hydroxyphenylme thyl Ρ 234 LV 10096

Table 12 TABLE 12

Example E1 BJ R22 E21 Number 5296 benzyl benzyl 2-methallyl 2-methallyl 5297 l-pyrolylmethyl l-pyrolylmethyl 4-methylpenty1 4-methylpentyl 5298 1- 1- 3-methallyl 3-oethallyl pyrazolylmethyl pyra zolylroethyl 5299 1- 1- 3-methylbutyl 3-methylbutyl imidazolylmethy 1 imidazolylmethy 5300 l-indolyln>ethyl l-indolylmethyl 3-methylpentyl 3-oethylpentyl 5301 2-pyridylmethyl 2-pyridylmethyl 3-pentyl 3-pentyl 5302 3-pyridylmethyl 3-pyridylmethyl 4 -methylpenty1 4-methylpentyl 5303 4-pyridylmethyl 4-pyridylmethyl 3,3-diroethallyl 3,3-dimethallyl 5304 Cyclohexylmethy cyclohexylmethy 3,3- 3,3- 1 1 dimethylbutyl dimethylbutyl 5305 2- 2- allyl allyl • thiophenylxnethy ļ thiophenylmethy 1 5306 (3,4- (3,4- cyclobutylmethy cyclobutylmethy methylenedioxyp methylenedioxyp 1 1 henyl)methyl henyl)inethyl 5307 2-thienylmethyl 2-thienylinethyl cyc lop ropylneth cyclopropylmeth yi yi 5308 4- 4- isobutyl isobutyl biphenylmethyl biphenylnvethyl 5309 2- 2- n-butyl n-butyl thiomethylethyl thiomethylethyl 5310 p- p- n-pentyl n-pentyl hydroxyphenylme hydroxyphenylme thyl thyl LV 10096 235 labie 12 5311 p- p- propyl propyl nitrophenylmeth nitrophenylmeth yi yi 5312 benzyl benzyl 2-methallyl H 5313 1-pyro ly lmethy 1 l-pyrolylmethyl 4-methylpentyl H 5314 1- 1- 3-methallyl H pyrazolylmethy1 pyrazolylmethyl 5315 1- 1- 3-methylbutyl H imida zolylmethy imidazolylmethy 1 5316 l-indolylmethyl l-indolylmethyl 3-methylpentyl H 5317 2-pyridylmethyl 2-pyridylmethyl 3-pentyl H 5318 3-pyridylmethyl 3-pyridylmethyl 4-methylpentyl H 5319 4-pyridylmethyl 4-pyridylmethy1 3,3-dimethallyl K 5320 cyc1ohexylmethy cyclohexylmethy 3,3- H 1 1 dimethylbutyl 5321 2- 2- allyl H thiophenylmethy ļ thiophenylmethy i 5322 (3,4- (3,4- cyclobutylmethy H methylenedioxyp xnethylenedioxyp 1 henyl)inethyl henyl)methyl 5323 2-thienylmethyl 2-thienylmethyl cyclopropylmeth yi iaobutyl H 5324 4- 4- H biphenylmethyl biphenylmethyl 5325 2- 2- n-butyl thiomethylethyl thiomethylethyl 5326 p- p- n-p«ntyl H hydroxyphenylme hydroxyphenylme thyl thyl 5327 p- p- propyl H nitrophenylmeth nitrophenylmeth yi yi 5328 benzyl p- nitrophenylmeth yi benzyl 2-methallyl 2-methallyl 5329 1-pyrolylroethy1 4-roethylpentyl 4-methylpentyl 5330 1- pyra zolylmethyl l-pyrolylmethyl 3-roethallyl 3-methallyl 5331 1- 1- 3-methylbutyl 3-methylbutyl imida zo ly lme thy * pyrazolylmethyl 5332 l-indolylmethyl 1- imidazolylmethy 1 3-methylpentyI 3-methylpentyl 5333 2-pyridylmethyl X l-indolylmethyl 3-pentyl 3-pentyl 5334 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-methylpentyl 5335 4-pyridylmethyl 3-pyridylmethyl ' 3,3-dimethallyl 3,3-dimetltallyl 5336 cyclohexylmethy 4-pyridylroethyl 3,3- 3,3- 1 diroethylbutyl dimethylbutyl 5337 2- cyclohexylmethy allyl allyl thiophenylmethy 1 1 236labie 12 5338 <3,4- 2- cydobutylmethy cyclobutyLnethy methylenedioxyp t h i ophe ny lrnethy 1 1 henyl)methyl 1 f 5339 2-thienylmethyl <3,4- ®ethylenedioxyp henyl)methyl cyclopropylmeth yi eyclopropylmeth yi 5340 4- biphenylmethyl 2-thienylmethyl lsobutyl isobutyl 5341 2- thiomethylethyl 4- biphenylnvethyl n-butyl n-butyl 5342 t>- hydroxyphenylroe thyl 2- thiomethylethyl n-pentyl n-pentyl 5343 p- nitrophenylmeth yi p- hydroxyphenylne thyl propyl propyl 5344 benzyl P“ nitrophenylmeth yi benzyl 2-nethallyl 2-methallyl 5345 l-pyrolylrnethyl 4-methylpentyl 4-methylpentyl 5346 1- pyra zolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 5347 1- imidazolylmethy 1 1- pyrazolylroethyl 3-methylbutyl 3-methylbutyl 5348 X l-indolylnvethyl 1- imidazolylmethy 1 3-roethylpentyl 3-methylpentyl 5349 2-pyridylmethy1 X l-indolylmethyl 3-pentyl 3-pentyl 5350 3-pyridylmethyl 2-pyridylnvethyl 4-methylpentyl 4-n»ethylpentyl 5351 4-pyridylmethyl 3-pyridylmethyl 3,3-diroethallyl 3,3-dimethallyl 5352 cyclohexylmethy 4-pyridy lmethyl 3,3- 3,3- 1 dinethylbutyl dimethylbutyl 5353 2- thiophenylmethy ļ cyclohexylmethy 1 . allyl allyl 5354 <3,4- 2- cyclobutyl®ethy cyclobutylmethy methylenedioxyp henyl)methyl thiophenylnvethy 1 1 1 5355 2-thienylmethyl <3,4- methylenedioxyp henyl)methyl cyclopropyloeth yi cyclopropylmeth yi 5356 4- biphenylmethyl 2-thienylmethyl isobutyl isobutyl 5357 2- thiomethylethyl 4- biphenylmethyl n-butyl n-butyl 5358 p- hydroxyphenylme thyl 2- thiomethylethyl n-pentyl n-pentyl 5359 p- nitrophenylmeth yi P“ hydroxyphenylme thyl propyl propyl 5360 benzyl p- nitropheny lmeth yi benzyl 2-methallyl propyl 5361 1-pytolylmethy1 4-methylpentyl 2-»ethallyl 237labie 12 LV 10096 5362 1- pyrazolylmethyl l-pyrolylmetbyl 3-methallyl 4-methylpentyl 5363 1- 1- 3-methylbutyl 3-roethallyl lmldazolylmethy 1 pyrazolylmethyl 5364 X l-indolylmethyl 1- 3-oethylpentyl 3-roethylbutyl _ iraida zolylioethy 1 5365 2-pyridy lmethyl X l-indolyl®ethyl 3rpentyi 3-methylpentyl 5366 3-pyridylmethyl 2-pyridylmethyl 4-oethylpentyl 3-pentyl 5367 4-pyridylmethy1 3-pyridylmethyl 3,3-dimethallyl 4-methylpentyl 5368 cyclohexylnethy 4-pyr idy lmethyl 3,3- 3,3-dimethallyl 1 dimethylbutyl 5369 2- cyclohexylmethy allyl 3,3- thiophenylnethy 1 1 diroethylbutyl 5370 <3,4- 2- cyclobutylmethy allyl methylenedioxyp thiophenylmethy 1 henyl)methyl 1 5371 2-thienyln>ethyl <3,4- cyclopropylroeth cyclobutylmethy methylenedioxyp henyl)methyl yi 1 5372 4- 2-thienylmethyl isobutyl cyclopropylmeth biphenylmethyl yi 5373 2- 4- n-butyl isobutyl thiomethylethyl biphenylroethyl 5374 p- 2- n-pentyl n-butyl hydroxyphenylme thyl thiomethylethyl 5375 p- p- propyl n-pentyl nitrophenylneth hydroxyphenylme yi thyl 238 labie 13 TABLE 13

gxample BJL L2 R22 Eaarcpla 537« benzyl benzyl 2-methallyl 2-methallyl 5377 l-pyrolylmethyl l-pyrolylroethyl 4-methylpentyl 4-methylpentyl 5378 1- 1- 3-methallyl 3-methallyl pyrazolylmethyl pyrazolylmethyl 5379 1- 1- 3-methylbutyl 3-methylbutyl imida zolylmethy imida zolylmethy 1 5380 l-indolylmethyl l-indolylmethyl 3-methylpentyl 3-»ethylpentyl 5381 2-pyridylmethyl 2-pyridylmethyl 3-pentyl 3-pentyl 5382 3-pyridylmethyl 3-pyridylmethyl 4-roethylpentyl 4-methylpentyl 5383 4-pyridylmethyl 4-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5384 cyclohexylmethy cyclohexylmethy 3,3- 3,3- 1 1 dimethylbutyl dimethylbutyl 5385 2- 2- allyl allyl thiophenylmethy ļ thiophenylmethy 1 5386 (3,4- (3,4- cyclobutylmethy cyclobutylmethy methylenedioxyp inethylenedioxyp 1 1 henyl}methyl henyl)nethyl 5387 2-thienylmethyl 2-thienylmethyl cyclopropylineth cyclopropylmeth yi yi 5388 4- 4- isobutyl isobutyl biphenylmethyl biphenylmethyl 4 5389 2· 2- n-butyl n-butyl thloxnethylethyl thiomethylethyl 5390 p- p- n-pentyl n-pentyl hydroxyphenylme hydroxyphenylme thyl thyl 239 LV 10096

Table 13 5391 p- p- propyl propyl nitrophenylmeth nitrophenylmeth yi yi 5392 benzyl benzyl 2-methallyl H 5393 1-pyrolylaethy1 l-pyrolylmethyl 4-methylpenty1 H 5394 1- 1- 3-methallyl H pyrazolylmethyl pyrazolylmethyl 5395 1- 1- 3-methylbutyl H imidazolylmethy 1 imida zolylmethy 1 5396 X l-indolylmethyl X 1-indolylmethy1 3-methylpentyl H 5397 2 -pyridylmethyl 2-pyridylmethyl 3-pentyl H 5398 3-pyridylmethyl 3-pyridylmethyl 4-methylpentyl K 5399 4-pyridylroethyl 4-pyridylmethyl 3,3-dimethallyl H 5400 cyclohexylmethy cyclohexylmethy 3,3- H 1 1 dimethylbutyl 5401 2- 2- allyl H thiophenylmethy 1 thiophenylmethy 1 5402 (3,4- (3,4- cyclobutylmethy H methylenedioxyp methylenedioxyp 1 henyl)methyl henyl)methyl 5403 2-thienylmethyl 2-thienylmethyl cyclopropy lmeth yi isobutyl H 5404 4- 4- H biphenylmethyl biphenylmethyl 5405 2- 2- n-butyl thiomethylethyl thiowethylethyl 5406 p- p- n-pentyl H hydroxyphenylme hydroxyphenylme thyl thyl 5407 P“ p- ptopyl H nitrophenylmeth n i trophenylmeth yi yi 5408 benzyl p- nitropheny lmeth yi benzyl 2-roethallyl 2-methallyl 5409 l-pyrolylmethyl 4-methylpentyl 4-methylpentyl 5410 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 3-methallyl 5411 1- 1- 3-roethylbutyl 3-methylbutyl imidazolylmethy pyrazolylmethyl 5412 X l-indolylroethyl 1- imidazolylmethy 3-methylpentyl 3-methylpentyl 5413 2-pyridylmethyl X l-indolylmethyl 3-pentyl 3-pentyl 5414 3-pyridylmethyl 2-pyridylmethyl, 4-methylpentyl 4-methylpentyl 5415 4-pyridylmethy1 3-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5416 cyclohexylmethy 4-pyridylmethyl 3,3- 3,3- 1 dimethylbutyl dlmethylbutyl 5417 2- cyelohexylmethy allyl allyl thiophenylmethy 1 - 1 240

Tahle 13 5418 <3,4- 2- cyclobutylmethy cyclobutylmethy methylenedioxyp thiophenylnvethy 1 1 henyl)methyl 1 5419 2-thienylmethyl <3,4- cyclopropyln»eth cyclopropylmeth methylenedioxyp henyl)methyl yi yi 5420. 4- biphenylmethyl 2-thieny lmethyl isobutyl isobutyl 5421 2- 4- n-butyl n-butyl thiomethylethyl biphenylmethyl 5422 p- 2- n-pentyl n-pentyl hydroxyphenylme thiomethylethyl thyl ’ 5423 p- p- propyl propyl nitrophenylaeth hydroxyphenylme yi thyl 5424 benzyl p- nitrophenylmeth yi benzyl 2-methallyl 2-methallyl 5425 l-pyrolylfliethyl 4 -inethy lpenty 1 4-methylpenty 1 5426 1- pyrazolyl®ethyl 1-pyrolylmethyl 3-methallyl 3-nethallyl 3-methylbutyl 5427 1- 1- 3-methylbutyl imida zolylmethy pyrazolylxnethyl 5428 «L l-indolyl»ethyl 1- imida zo ly linethy 1 3-methylpentyl 3 -ine thy lpent y 1 5429 2-pyridylmethyl X 1-indolylmethyl 3-pentyl 3-pentyl 5430 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 4-©ethylpentyl 5431 4-pyridylmethyl 3-pyridylmethyl 3,3-dimethallyl 3,3-dimethallyl 5432 cyclohexylmethy 4-pyridylmethyl 3,3- 3,3- 1 dimethylbutyl dinethylbutyl 5433 2- cyclohexylmethy allyl allyl thiophenylmethy 1 5434 <3,4- 2- cyclobutylmethy cyclobutyljnethy methylenedioxyp thiophenylmethy 1 1 henyl)methyl 1 5435 2-thienylroethyl (3, 4- cyclopropylmeth cyclopropylmeth methylenedioxyp henyl)methyl yi y! 5436 4- biphenylmethyl 2 -thieny lirvethyl lsobutyl iaobutyl 5437 2- 4- n-butyl n-butyl thiomethylethyl biphenylmethyl 5438 p- 2- n-pentyl n-pentyl hydroxyphenylme thyl thiomethylethyl 5439 p- p- propyl propyl * nitrophenylmeth hydroxyphenylme yi thyl 5440 benzyl p- nltcophenylmeth yi benzyl 2-methallyl propyl S441 l-pyrolylmethyl 4-roethylpentyl 2-methallyl 241 LV 10096 Iafale-13 5442 1- pyrazolylmethyl l-pyrolylmethyl 3-methallyl 4-methylpentyl 3-methallyl 5443 1- 1- 3-methylbutyl imidazolylmethy pyrazolylmethyl 5444 4 l-indolylmethyl 1- 3-methylpentyl 3-methylbutyl iroidazolylmethy 1 5445 2-pyridylmethyl l-indolyliftethyl 3-pentyl 3-methylpentyl 5446 3-pyridyLnethyl 2-pyridylmethy1 4-methylpentyl 3-pentyl 5447 4-pyridylmethyl 3-pyridylxnethyl 3, 3-dimethallyl 4-methylpentyl 5448 cyclohexylnethy 4-pyridyl»ethyl 3,3- 3,3-dimethally; 1 dimethylbutyl 5449 2· cyclohexylmethy allyl 3,3- thiophenylnethy ļ 1 diinethylbutyl 5450 (3,4- 2- cyclobutylmethy allyl . nethylenedioxyp thiophenylmethy 1 henyl)methyl 1 5451 2-thienylmethy 1 (3,4- cyclopropylmeth cyclobutylmeth ntethylenedioxyp henyl)methyl yi 1 S452 4- 2-thienylmethyl iaobutyl cyclopropylmet biphenylmethyl yi 5453 2- 4- n-butyl isobutyl thiomethylethyl biphenylmethyl 5454 p- 2- n-pentyl n-butyl hydroxypheny lae thyl thiomethylethyl 5455 p- p- propyl n-pentyl nitrophenylmeth hydroxyphenylme yi thyl 242

Table 14 TABLE 14 0

Example E2 R22 Humfees 5456 benzyl benzyl 2-methallyl 5457 l-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 5458 l-pyrazolylmethyl l-pyrazolylmethyl 3-methallyl 5459 1- imidazolylmethyl 1- imidazolylaethyl 3-methylbutyl 5460 l-indolylmethyl l-indolylaethyl 3-methylpentyl 5461 2-pyridylmethyl 2-pyridyl»ethyl 3-pentyl 5462 3-pyridylmethyl 3-pyridylmethyl 4-methylpentyl 5463 4-pyridylwethyl 4-pyridylmethyl 3,3-diinethallyl 5464 cyclohexylaethyl cyc1ohe xyl»ethy1 3,3-dimethylbutyl 5465 2- thiophenylxaethyl 2- thiophenylmethyl allyl 5466 <3,4- methylenedioxyphe nyl)methyl <3,4- methylenedioxyphe nyl)methyl cyclobutylaethyl 5467 2-thienylmethyl 2-thienylmethyl cyclopropylmethyl 5468 4-biphenylmethyl 4-biphenylroethyl lsobutyl 5469 2-thlomethylethyl 2-thiomethylethyl n-butyl 5470 p- hydroxyphenylmeth yi p- hydroxyphenylmeth yi n-pentyl 5471 p- nitropheny lmethy1 p- nltrophenylmethyl propyl 5472 benzyl benzyl 2-<nethallyl S473 l-pyrolylmethyl 1-pyrolylmethy1 4-methylpentyl 5474 1-pyr a zoly lmethyl l-pyrazolylmethyl 3-methallyl 5475 1- imidazolylmethyl 1- imida z oly lmethyl 3-methylbutyl 5476 l-indolylmethyl l-indolylmethyl 3-methylpentyl

labie _1A 5477 2-pyridylmethyl 2-pyridylmethyl 3-pentyl 5478 3-pyridylmethyl 3-pyridylmethyl 4-methylpentyl 5479 4-pyridylmethyl 4-pyridylraethyl 3,3-dimethallyl 5480 cyclohexylmethyl cyclohexylmethyl 3,3-dimethylbutyl 5481 2- 2- allyl thiophenylmethyl thiophenylmethyl 5482 (3,4- (3,4- cyclobutylmethyl methylenedioxyphe nethylenedioxyphe nyl)methyl nyl)methyl 5483 2-thienylmethyl 2-thienylmethyl cyclopropylmethyl 5484 4-biphenylroethyl 4-biphenylmethy1 isobutyl 5485 2-thiomethylethyl 2-thiomethylethyl n-butyl 5486 p- p- n-pentyl hydroxyphenylmeth hydroxyphenylmeth yi yi propyl 5487 p- p- nit rophenylmethyl nitrophenylnvethyl 5488 benzyl p- nitrophenylmethyl 2-methallyl 5489 l-pyrolylmethyl benzyl 4-methylpentyl 5490 1-py r a zolylmethyl l-pyrolylmethyl 3-methallyl 5491 1- imida z o ly lme thy 1 l-pyrazolylmethyl 3-methylbutyl 5492 1-indolylmethyl 1- imida zolylmethyl 3-methylpentyl 5493 2-pyridylmethyl l-indolylmethyl 3-pentyl 5494 3-pyridylmethyl 2-pyridylmethyl 4-methylpentyl 5495 4-pyridylmethyl 3-pyridylmethy1 3,3-dimethallyl 5496 cyclohexylmethyl 4-pyridylmethyl 3,3-dimethylbutyl 5497 2- thiophenylmethyl cyclohexylmethyl allyl 5498 (3,4- 2- cyclobutylmethyl methylenedioxyphe nyl)methyl ‘ thiophenylmethy1 5499 2-thienylmethyl (3,4- methylenedioxyphe nyl)methyl cyclopropylmethyl 5500 4-biphenylaethyl 2-thienylmethyl isobutyl 5501 2-thiomethylethyl 4-biphenylmethyl n-butyl 5502 p- hydroxyphenylmeth yi p- 2-thiomethylethyl n-pentyl 5503 p- hydroxyphenylmeth yi p- propyl nit rophenylmethyl 5504 benzyl 2-methallyl nit rophenylmethyl 5505 l-pyrolylmethyl benzyl 4-methylpentyl 5506 1-pyrazolylmethyl 1-pyrolylmethy1 3-oethallyl 5507 1- imlda z o ly la» thy 1 l-pyrazolylmethyl 3-methylbutyl 5508 l-lndolylnethyl 1- imldazolylmethyl 3-methylpentyl 5509 2-pyr idyl®ethy1 l-indolylmethyl 3-pentyl 244

Table 14 5510 3-pyridyl©ethyl 2-pyridylmethyl 4-jnethylpentyl 5511 4“pyridyln*thyl • 3-pyridylmethyl 3,3-diroethallyl 5512 cyclohexylmethy1 4-pyridylmethy1 3,3-dimethylbutyl 5513 2- thiophenylmethyl cyclohexylmethyl allyl 5514 <3,4- 2- cyclobutylmethyl nethylenedioxyphe nyl)wethyl thiophenylmethyl 5515 2-thienylmethyl €3,4- methylenedioxyphe nyl)nethyl cyclopropylnethy1 5516 4-biphenylmethyl 2-thienylmethyl lsobutyl 5517 2-thiomethylethyl 4-biphenylmethy1 n-butyl 5518 P“ hydroxyphenylmeth yi p- 2-thlomethylethyl n-pentyl 5S19 p- hydroxyphenylmeth yi p- propyl nitrophenylmethyl 5520 benzyl 2-tnethallyl nitrophenylmethyl 5521 l-pyrolylmethyl benzyl 4-methylpentyl 5522 l-pyrazolylmethyl l-pyrolylmethyl 3-methallyl 5523 1- imida zolylnethyl l-pyra zolylmethyl 3-®ethylbutyl 5524 l-indolylmethyl 1- imida z o ly lme thy 1 3-»ethylpentyl 5525 2-pyridyl®ethyl 1 -indo ly lmet hy 1 3-pentyl 5526 3-pyridybnethyl 2-pyridylmethyl 4-methylpentyl 5527 4-pyridylmethyl 3-pyridylmethyl 3,3-diroethallyl 5528 cyclohexyl»ethyl 4-pyridyl»ethyl 3,3-dimethylbutyl 5529 2- thiophenylmethyl cyclohexyla>ethyl allyl 5530 <3,4- 2- cyclobutyloethyl jnethylenedioxyphe nyl)methyl thlophenylmethyl 5531 2-thienylmethyl €3,4- methylenedioxyphe nyl)methyl cyclopropylmethyl 5532 4-biphenylmethyl 2-thienylmethyl iaobutyl 5533 2-thiomethylethyl 4-biphenylmethy1 n-butyl 5534 p- hydroxyphenylmeth yi p- 2-thiomethylethyl n-pentyl 5535 p- propyl nitropheny lmethy1 hydroxyphenylmeth yi 4 245 LV 10096 TABLE 15

EgAmplA EJ. Itf E21 Numbeg 5536 benryl benzyl 2>methallyl 5537 l-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 5538 l-pyrazolylmethyl l-pyrazolylmethyl 3-methallyl 5539 1- 1- 3-methylbutyl imidazolylmethyl imida zolylmethyl 5540 l-indolylmethyl 1-indolylmethy1 3-methylpentyl 5541 2-pyridylroethyl 2-pyridylmethyl 3-pentyl 5542 3-pyridylmethyl 3-pyridylmethyl 4-methylpentyl 5543 4-pyridylmethyl 4-pyridylmethyl 3,3-dimethallyl 5544 cyclohexylmethyl cyclohexylmethyl 3,3-dimethylbutyl 5545 2· 2- allyl thiophenylmethyl thiophenylmethyl 5546 (3, 4- (3,4- cyclobutylmethyl methylenedioxyphe methylenedioxyph« nyl)roethyl nyl)methyl 5547 2-thienylmethyl 2-th ienylmethyl cyclopropylmethy1 5548 4-biphenyl»ethyl 4-biphenylmethy1 isobutyl 5549 2-thiomethylethyl 2-thioroethylethyl n-butyl 5550 p- p- n-pentyl hydroxyphenylmeth hydroxyphenylmeth yi yi 5551 p- p- propyl nitrophenylmethyl nit rophenylmethyl 5552 benzyl benzyl 2-methallyl 5553 l-pyrolylmethyl l-pyrolylmethyl 4-methylpentyl 5554 1-pyrazolylmethyl l-pyra zolylinethyl 3-methallyl 5555 1- 1- 3-n>ethylbutyl imida zoly lmethyl imida zolylmethyl 55S6 l-indolylmethyl l-indolylroethyl 3-methylpentyl 246 lablg-15 5557 2-pyridylmethyl .2-pyridylmethyl 3-pentyl 5558 3-py r idyljne thy 1 3-pyridylwethyl ,· 4-methylpentyl 5559 4-pyridyl®ethyl 4-pyridyln»ethyl 3,3-dimethallyl 5560 cyclohexylmethyl cyclohexylmethyl 3,3-dimethylbutyl 5561 2- 2- allyl thiophenylmethyl thiophenylmethyl 5562 (3,4- (3,4- cyclobutylmethyl methylenedioxyphe methylenedioxyphe nyl)methyl nyl)methyl 5563 2-thienylmethyl 2-thienylmethyl cyclopropylmethyl 5564 4-biphenylmethyl 4-biphenylmethyl iaobutyl 5565 2 -1 h iome thyIethy1 2-thiomethylethyl n-butyl 5566 p- p- n-pentyl hydroxyphenylmeth hydroxyphenylmeth yi yi 5567 p- p- propyl nit rophenylnethyl nitrophenylmethyl 5568 benzyl p- nit rophenylmethyl 2-methallyl 5569 l-pyrolylxiethyl benzyl 4-methylpentyl 5570 l-pyrazolylmethyl l-pyrolylmethyl 3-methallyl 5571 1- imidazolylroethyl l-pyrazolylmethyl 3-methylbutyl 5572 l-indolylmethyl 1- inddazolylroethyl 3-roethylpentyl 5573 2-pyridylmethyl l-indolylmethyl 3-pentyl 5574 3-pyridylmethyl 2 -py r i dy lnvethyl 4-roethylpentyl 5575 4-pyridyLnethyl 3-pyridylmethyl 3,3-dimethallyl 5576 cyclohexylaethyl 4-pyridylmethyl 3,3-dimethylbutyl 5577 2- thiophenyla>ethyl cyclohexylmethyl allyl 5578 (3,4- 2- cyclobutylmethyl methylenedioxyphe nyl)methyl thiophenylmethyl cyclopropylavethyl 5579 2-thienyhnethyl (3,4- methylenedioxyphe nyl)methyl 5580 4 -biphenylmethyl 2-thienylxnethyl isobutyl 5581 2-thiomethylethyl 4-biphenylmethyl n-butyl 5582 p- hydroxyphenylmeth yi p- 2-thiomethylethyl n-pentyl 5583 p- hydroxyphenylmeth yi p- propyl nit r ophenylxnethyl 5584 benzyl 2-methallyl nit rophenylmethyl 5585 l-pyrolylmethyl benzyl 4-methylpentyl 5586 l-pyrazolylmethyl 1-pyrolylmethyl 3-roethallyl 5587 1- iraida zolylnethyl l-pyrazolylmethyl 3-methylbutyl 5588 l-indolylmethyl 1- imida zo ly lmethy 1 3-methylpentyl 5589 2-pyridy l®ethyl 1-iņdolylmethyl 3-pentyl 247 LV 10096

labie 1S 5590 3-pyridyln>ethyl 2-pyridylmethyl 4-methylpentyl 5591 4-pyridylmethyl 3-pyridylmethyl 3,3-dimethallyl 5592 cyclohexylmethyl 4-pyridylmethyl 3,3-dimethylbutyl 5593 2- thiophenylmethyl cyclohexylmethyl allyl 5594 <3,4- 2- cyclobutylroethyl methylenedioxyphe nyl)methyl. thiophenylmethyl 5595 2 -thienylmethyl (3,4- »ethylenedioxyphe nyl)methyl cyclopropylmethyl 5596 4-biphenylmethy1' 2-thienylmethyl isobutyl 5597 2-thiomethylethyl 4-biphenylmethyl n-butyl 559B p- hydroxyphenylmeth yi p- 2-thiomethylethyl n-pentyl 5599 p- hydroxyphenylmeth yi p- propyl nitrophenylmethyl 5600 benzyl 2-methallyl nitrophenylmethyl 5601 l-pyrolylmethyl benzyl 4-methylpentyl 5602 l-pyrazolylmethyl l-pyrolylmethyl 3-methallyl 5603 1- imida zolylmethyl l-pyrazolylmethyl 3-methylbutyl 5604 l-indolyl»ethyl 1- imidazolylmethyl 3-methylpentyl 5605 2-pyridylmethyl 1-indolylmethyl 3-pentyl 5606 3-pyridylmethyl 2-pyridylroethyl 4-methylpentyl 5607 4-pyridylmethyl 3-pyridylmethyl 3,3-dimethallyl 5608 cyclohexylmethyl 4-pyridylmethyl 3,3-dimethylbutyl 5609 2- thiophenylmethyl cyclohexylmethyl allyl 5610 (3,4- 2- cyclobutyLnethyl methylenedioxyphe thiophenylmethyl 5611 nyl)methyl 2-thienylmethyl (3,4- methylenedioxyphe nyl)methyl cyclopropylirvethyl 5612 4 -biphenylmethyl 2-thienylmethyl isobutyl 5613 2-thiomethylethyl 4-biphenylmethyl n-butyl 5614 p- hydroxyphenylmeth yi p- 2-thioroethylethyl n-pentyl 5615 p- propyl nitrophenylrnethyl hydroxyphenylmeth yi 248

. « 249 LV 10096

GLAIMS WHAT IS CLAIMED IS: 1. A compound of the formula (I):

(I) or a pharmaceutically acceptable salt or prodrug form thereof wherein: R4 and R7 are independently selected from the following groups: hydrogen; Οχ-08 alkyl substituted with 0-3 R11; C2-C8 alkenyl substituted with 0-3 R11; C2-C8 alkynyl substituted with 0-3 R^; C3-C8 cycloalkyl substituted with 0-3 R1*; c6'c10 bicycloalkyl substituted with 0-3 R11; aryl substituted with 0-3 R12; a C6-C14 carbocyclic residue substituted with 0-3 r12; a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 250 R^a and R7A are independently selected from the following groups: hydrogen; C1-C4 alkyl substituted with halogen or C1-C2 alkoxy; benzyl substituted with halogen or C1-C2 alkoxy; R^ and R4A can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R12; R7 and R7a can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R12; n is 0/ 1, or 2; R5 is selected from fluoro, difluoro, =0, C1-C3 alkyl or -OR20; R®, when n is 1, is selected from: hydrogen, =0, fluoro, difluoro, C1-C3 alkyl or -OR21; R®, when n is 2, is independently selected from: hydrogen, =0, fluoro, difluoro, C1-C3 alkyl or -OR21; R^ and r6 can alternatively join to form an epoxide ring; R20 and R21 are independently selected from: hydrogen; C1-C6 alkyl substituted with 0-3 R11; C3-C6 alkoxyalkyl substituted with 0-3 R11; C1-C6 alkylcarbonyl substituted with 0-3 R11; C1-C6 alkoxycarbonyl substituted with 0-3 R11; benzoyl substituted with 0-3 R12; 251 LV 10096 phenoxycarbonyl substituted with 0-3 R12; phenylaminocarbonyl substituted with 0-3 R12;or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl; 5 R11 is selected from one or more of the follov/ing: keto, halogen, cyano, -NR13R14, -CO2R13. -0C(=0)R13, -OR13, C2-C6 alkoxyalkyl, -S(0)mR13, 10 -NHC (=NH) NHR13, -C(=NH)NHR13, -C(=0)NR13R14, -NR14C(=0)R13, =NOR14, -NR14C(=0)0R14, -0C(=0)NR13R14, -NR13C(=0)NR13R14, -NR14S02NR13R14, -NR14S02R13, -S02NR13R14, C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl; 15 1-3 amino acids, linked together via amide bonds and linked to R4 or R7 via the amine or carboxylate terminus; 20 a C5-C14 carbocyclic residue substituted with 0-3 R12; aryl substituted with 0-3 R12; or 25 a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 30 R12, when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C4 alkyl, C3-C6 35 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -NR13R14, C2-C6 alkoxyalkyl, C1-C4 252 hydroxyalkyl, methylenedioxy, ethylenedioxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylami.no, -S(0)jnR13, -S02NR13r14, 5 -NHSO2R*4, -OCH2CO2H, 2-(l-morpholino)ethoxy; or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms’selected from oxygen, nitrogen or sulfur; 10 or r!2 may be a 3- or 4- carbon chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6- membered ring being optionally substituted on the aliphatic carbons with 15 halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, or -NR13R14; or, when R1^ ļs attached to a saturated carbon atom, it may be carbonyl or thiocarbonyl; r12# when a substituent on nitrogen, is selected from 20 one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, -NR13R14, C2-C6 25 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl; r13 is H, phenyl, benzyl or C1-C6 alkyl; 3 0 R14 is H or C1-C4 alkyl; r!3 and Rl4 can alternatively join to form -(CH2)4-, -(CH2)5"» -CH2CH2N(R15)CH2CH2", or -CH2CH2OCH2CH2-; 3 5 R15 is H or CH3; 253 LV 10096 m is 0, 1 or 2; W is selected from: -N(R22)C(=Z)N(R23)-; -N(R22)S(=0)N(R23)-; -OC(=Z)0-; -N(R22)C(=Z)0-; -C(R25) (R26)C(=Z.)C(R27) (R28)-; -N(R22)C(=Z)C(R27)(R28)-; 10 -C{R25) (R26)C(=Z)0-; -N(R22)C(=0)C(=0)N(R23)-; 15 -C(R25)(R26)C(F2)C(R27)(R28)-; -C(R25)(R26)N(CH3)(O)C(R27)(R28) -C(R25) (R26)N(OR29)C(R27)(R28)-; -C(R25)(R26)C(=Z)S-; wherein: Z is 0, S, or NR24; 20 R22 and R23 are independently selected from the folloving: hydrogen; 25 C1-C8 alkyl substituted with 0-3 r11; C2-C8 alkenyl substituted with 0-3 R3·1; C2-C8 alkynyl substituted with 0-3 R3·3·; C3-C8 cycloalkyl substituted with 0-3 R3·3·; 30 C6-C10 bicycloalkyl substituted with 0-3 R3-3·; aryl substituted with 0-3 R3·2; a C6-C14 carbocyclic residue substituted with 0-3 R12; a heterocyclic ring system substituted with 0-2 R3·2, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 35 254 r24 is selected from: hydroxy; amino; C1-C4 alkyl; C1-C4 alkoxy; C1-C4 aminoalkyl; R25 and R27 are independently selected from the '5 follov/ing: hydrogen; C1-C8 alkyl substituted with 0-3 r11; C2-C8 alkenyl substituted with 0-3 R11; 10 C2-C8 alkynyl substituted with 0-3 R^; C3-C8 cycloalkyl substituted with 0-3 R11? C6-C10 bicycloalkyl substituted with 0-3 rH; aryl substituted with 0-3 R*2; a C6-C14 carbocyclic residue substituted with 0-3 15 R12; a heterocyclic ring system substituted with 0-2 R*2, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 20 R2® and R2® are independently selected from: hydrogen; C1-C4 alkyl substituted with halogen or C1-C2 alkoxy; 25 benzyl substituted with halogen or C1-C2 alkoxy; r29 is selected from: hydrogen; 30 C1-C4 alkyl substituted with halogen or C1-C2 alkoxy; benzyl substituted with halogen or C1-C2 alkoxy; 35 alternatively, R22, R2^, or R2®, independently, can join with R^ or R*a to form a five- or six-membered fused 256 C3-C4 alkenyl substituted with 0-3 R11; C3-C4 alkynyl substituted with 0-3 R11; r^A and R^A are hydrogen; 5 n is 0 or 1; R5 is selected from fluoro, difluoro, =0, or -OR2^; 10 r6 is selected from: hydrogen, =0, fluoro, difluoro, or -OR21; r2Ū and R21 are independently selected from: 15 hydrogen; C1-C6 alkylcarbonyl; C1-C6 alkoxycarbonyl; benzoyl; or any group that, when administered to a mammalian 2 0 subject, cleaves to form a free hydroxyl; R11 is selected from one or more of the following: 25 keto, halogen, cyano, -NR11R1^, -CO2R13# -OC(=0)R13, -OR13, C2-C4 alkoxyalkyl, -S(0)mR13, C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl; a C5-C14 carbocyclic residue substituted with 0-3 30 R12; aryl substituted with 0-3 R12; or a heterocyclic ring system substituted with 0-2 35 R12, composed of 5 to 10 atoms including at least one nitrogen, oxygen or sulfur atom; 255 LV 10096 heterocyclic, aromatic, or alicyclic ring substituted with 0-2 R1^; and alternatively, R^3, r27, or R28/ independently, can join 5 vith R7 or R7A to form a five- or six-membered fused heterocyclic, aromatic, or alicyclic ring substituted with 0-2 r12; provided that: 10 when is hydrogen, R7 is not hydrogen; when W is -0C(=Z)0-, R^ and R7 are not hydrogen; 15 when R* is hydrogen, at least one of the £ollowing is not hydrogen: R22, r23# r25# r26# r27 and r28^ 2. A compound of Claim 1 of formula (I): 20

(i) or a pharmaceutically acceptable salt or prodrug form 25 thereof wherein: R1 2 and R7 are independently selected from the following groups: 1 0 hydrogen; 2 C1-C4 alkyl substituted with 0-3 r11; 257 257 LV 10096 when a substituent on carbon, is selected from one or more of the following: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy# nitro, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -NR^R3·4, C2-C6 alkoxyalkyl, C1-C4 hydroxyalkyl, methylenedioxy, ethylenedioxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxycarbonylf C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylamino, -S(0)mR^* -S02NR13R14, -NHSO2R14? or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; or R1^ may be a 3- or 4- carbon Chain attached to adjacent carbons on the ring to form a fused 5- or 6-membered ring, said 5- or 6- membered ring being optionally substituted on the aliphatic carbons with halogen, C1-C4 alkyl, C1-C4 alkoxy, hydroxy, or -NrI3r1 4; or, when R3·^ is attached to a saturated carbon atom, it may be carbonyl or thiocarbonyl ; r!2, when a substituent on nitrogen, is selected from one or more of the following: phenyl, benzyl, phenethyl, hydroxy, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, -NR13R14, C2-C6 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyloxy, C1-C4 alkylcarbonyl; 258 R13 is H or C1-C6 alkyl; R*4 is H, C1-C4 alkyl, or benzyl; R13 and R14 can alternatively join to form -(CH2)4 -(CH2)5-. or -CH2CH20CH2CH2-

RlS is H or CH3; m is 0, 1 or 2; W is selected from: -N(r22)c(s:Z)N(R23)-; -N(r22)C(=Z)0-; -C(r25)(r26)c(=Z)c(r27) (r28)-· -N(r22)c(=z)C(r27)(r28)_. -C(r25){r26)c{=Z)0-; -N(R22)C(aO)C(=0)N(R23)-; -C(R25j(r26)C(F2)c(r27)(r28).; wherein: Z is 0; R22 and R23 are independently selected from the following: hydrogen; C1-C8 alkyl substituted with 0-3 R^·? C3-C8 alkenyl substituted with 0-3 R3·^·; C3-C8 alkynyl substituted with 0-3 r33; C3-C6 cycloalkyl substituted with 0-3 R11; r25 and R27 are independently selected from the following: 259 LV 10096 hydrogen; C1-C8 alkyl substituted with 0-3 R1·1; C2-C8 alkenyl substituted with 0-3 R^·; 5 C3-C8 alkynyl substituted with 0-3 R^·; r26 and R2** are hydrogen; provided that: 10 when R4 is hydrogen, R7 is not hydrogen; when w is -0C(=Z)0-, R4 and R7 are not hydrogen; 1 5 when R4 is hydrogen, at least one of the folloving is not hydrogen: R22, R22, R2^, R2^, R27 and R2®. 3. A compound of Claim 1 of formula (II): 20 R4

R7 (II) 25 or a pharmaceutically acceptable salt or prodrug form thereof wherein: R4 and R7 are independently selected from the following groups: hydrogen; C1-C4 alkyl substituted with 0-3 R1*; C3-C4 alkenyl substituted with 0-3 R1*; 5 260 R5 is -OR20; R6 is hydrogen or -OR2*; r20 and r21 are independently hydrogen or any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl; 10

Rll is selected from one or more of the following: keto, halogen, -NR^R1^ -ORC2-C4 alkoxyalkyl, C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl; 15 aryl substituted with 0-3 R*2; or a heterocyclic ring system substituted with 0-2 R12, composed of 5 to 10 atoms including at least 20 one nitrogen, oxygen or sulfur atom; R*2, when a substituent on carbon, is selected from one or more of the folloving: 25 phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, C1-C4 alkyl, C7-C10 arylalkyl, C1-C4 alkoxy, -NR13R14, methylenedioxy, C1-C4 haloalkyl, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylamino; or 30 a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; 35 R12, when a substituent on nitrogen, is selected from benzyl or methyl; 261 261 LV 10096

Rl3 is H or C1-C2 alkyl; R14 is H or C1-C2 alkyl; R13 and R14 can alternatively join to form -(CH2)4-, - (CH2) 5"* -CH2CH2N(R15)CH2CH2-, or -CH2CH2OCH2CH2-; W is selected from: -N(R22)C(=Z)N(R23)-; -C(R25) (R26)C(=Z)C(R27)(R28)-; -N(R22)C(=Z)C(R27)(R28)-; -C(R25)(R26)C{=Z)0-; wherein: Z is 0; R22 and R23 are independently selected from the following: hydrogen; C1-C4 alkyl substituted with 0-3 R1^; C3-C4 alkenyl substituted with 0-3 R11; R23 and R27 are independently selected from the following: hydrogen; C1-C4 alkyl substituted with 0-3 RŪ; C3-C4 alkenyl substituted with 0-3 R13·; R26 and R28 are hydrogen; provided that: 262 when R4 is hydrogen, R7 is not hydrogen; when R4 is hydrogen, at least one of the following is not hydrogen: R22, r23# r25# r26# r27 an(j r28# 4. A compound of Claim 3 wherein: R4 and R7 are independently selected from the following groups: hydrogen; C1-C3 alkyl substituted with 0-1 R11; R5 is -OR20; R6 is hydrogen or -0R2'!; R20 and R2! are independently hydrogen or any group thatj when administered to a mammaiian subject, cleaves to form a free hydroxyl;

Rll is selected from one or more of the following: halogen, -Or13, C1-C4 alkyl, C5-C6 cycloalkyl; aryl substituted with 0-2 R12; or a heterocyclic ring system chosen from pyridylf pyrimidinyl, triazinyl, furanyl, thienylf pyrrolyl, pyrazolyl# imidazolyl, tetrazolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl; 263 263 LV 10096 R*2, when a substituent on carbon, is selected from one or more of the following: benzyloxy, halogen, methyl, C1-C4 alkoxy,CF3, 2-(1-5 morpholino)ethoxy; or R^-2, when a substituent on nitrogen, is methyl;

Rl3 is H or methyl; 10 is H or methyl; R^·3 and R^ can alternatively join to form -(CH2)4-, ~(CH2)5"· -CH2CH2N(R15)CH2CH2-, or -CH2CH20CH2CH2-? 15 W is -N(R22)C(=0)N(R23)-; wherein: 20 R22 and R23 are independently selected from the following: hydrogen; C1-C4 alkyl substituted with 0-1 R1*; 25 C3-C4 alkenyl substituted with 0-1 R^; provided that: when R4 is hydrogen, R^ is not hydrogen; 30 when R4 is hydrogen, at least one of the following is not hydrogen: R22 and R23. 35 5. A compound of Claim 1 of formula (Ila): 264

(Ila) which is selected from the group consisting of: the compound of formula (Ila) v/herein R22 ļs h and R23 is H; the compound of formula (Ila) wherein R22 is allyl and 10 R23 is allyl; the compound of formula (Ila) wherein R22 is 3,7-dimethyl-l-octyl and R23 is 3,7-dimethyl-l-octyl; 15 the compound of formula (Ila) vherein R22 is CH2CH2OCH2CH2OCH3 and R23 is CH2CH2OCH2CH2OCH3; the compound of formula (Ila) wherein R22 is 3,7-dimethyl-l-octyl and R23 is H; 20 the compound of formula (Ila) wherein R22 is (CH2CH2O)3CH3 and R23 is H; the compound of formula (Ila) wherein R22 is 25 (CH2CH2O)3CH3 and R23 is (CH2CH20)3CH3; the compound of formula (Ila) wherein R22 is CH2CH2OH and R23 is CH2CH2NHCH(CH(CH3)2)C(=0)0-benzyl? 265 LV 10096 the compound of formula (Ila) wherein R22 is CH2CH2NHCH (CH (CH3) 2)C (=0)0-benzyl and R23 is 'CH2CH2NHCH(CH{CH3)2)c(=0)0-benzyl ; 5 the compound of formula (Ila) vherein R22 is propyl and r23 is propyl; the compound of formula (Ila) wherein R22 is methyl and r23 is methyl; 10 the compound of formula (Ila) vherein R22 is cyclopropylmethyl and R23 is cyclopropylmethyl; the compound of formula (Ila) wherein R22 is n-hexyl and 15 r23 ļs n-hexyl; the compound of formula (Ila) wherein R22 is n-butyl and R23 is n-butyl; 20 the compound of formula (Ila) wherein R22 is N- morpholinoethyl and R23 is N-morpholinoethyl; the compound of formula (Ila) wherein R22 is n-heptyl and R23 is n-heptyl; 25 the compound of formula (Ila) wherein R22 is CH2CH=CH(CH3)2 and R23 is CH2CH=CH(CH3)2» the compound of formula (Ila) wherein R22 is ethyl and 30 r23 ļg ethyl; the compound of formula (Ila) wherein R22 is CH2CH=CH(CH3)2 and R23 is H? the compound of formula (Ila) wherein R22 is i-pentyl and R23 is i-pentyl; 266 the compound of formula (Ila) wherein R22 is 4-pyridylmethyl and R23 is 4-pyridylmethyl; the compound of formula (Ila) wherein R22 is 2-methallyl and R23 is 2-methallyl; the compound of formula (Ila) wherein R22 ļs n-pentyl and R23 is n-pentyl; the compound of formula (Ila) wherein R22 is i-octyl and r23 is i-octyl; the compound of formula (Ila) wherein R22 is i-hexyl and R23 is i-hexyl; the compound of formula (Ila) wherein R22 is i-heptyl and R23 is i-heptyl; the compound of formula (Ila) wherein R22 is i-butyl and R23 is i-butyl; the compound of formula (Ila) wherein R22 is 3-propargyl and R23 is 3-propargyl; the compound of formula (Ila) vherein R22 is benzyl and R23 is benzyl; the compound of formula (Ila) wherein R22 is 2-pyridylmethyl and R23 is 2-pyridylmethyl; the compound of formula (Ila) wherein R22 is phenylpropyl and R23 is phenylpropyl; the compound of formula (Ila) vherein R22 is allyl and r23 is isoprenyl; 267 LV 10096 the compound of formula (Ila) vherein R22 is l-cinnamyl and R23 ļs l-cinnamyl. 5 6. A compound of Claim 1 of formula (Ila) :

(Ila) 10 which is selected from the group consisting of: the compound of formula (Ila) vherein R22 is allyl and r23 is allyl; 15 the compound of formula (Ila) vherein R22 is propyl and r23 is propyl; the compound of formula (Ila) vherein R22 is 20 cyclopropylmethyl and R23 is cyclopropylmethyl; the compound of formula (Ila) vherein R22 is n-hexyl and r23 is n-hexyl; 25 the compound of formula (ila) vherein R22 is n-butyl and r23 is n-butyl; the compound of formula (Ila) vherein R22 is CH2CH=CH(CH3)2 and R23 is CH2CH=CH (CH3) 2 * 30 268 the compound of formula CH2CH2CH(CH2)2 and R23 is H; the compound of formula 5 and R23 is i-pentyl; the compound of formula and R23 is 2-methallyl; ' 10 the compound of formula and R23 is n-pentyl; the compound of formula R23 is i-hexyl; 15 the compound of formula r23 is benzyl; the compound of formula 20 R23 is isoprenyl; the compound of formula and R23 is l-cinnamyl. (Ila) vherein R22 is (Ila) wherein R22 is i-pentyl (Ila) vherein R22 is 2-methallyl (Ila) vherein R22 is n-pentyl (Ila) vherein R22 is i-hexyl and (Ila) vherein R22 is benzyl and (Ila) vherein R22 is allyl and (Ila) vherein R22 is l-cinnamyl 25 7. A compound of Claim 1 of formula (Ila):

(Ila) vhich is selected from the group consisting of: 30 269 LV 10096 the compound of formula (Ila) vherein r22 is allyl and r23 is allyl; 5 the compound of formula (Ila) wherein r22 is cyclopropylmethyl and r23 is cyclopropylmethyl; the compound of formula (Ila) vherein r22 is n-butyl and r23 is n-butyl; 10 the compound of formula (Ila) wherein r22 is CH2CH=CH(CH3)2 and R23 is CH2CH=CH(CH3)2; the compound of formula (Ila) wherein r22 is propyl 15 and r23 is propyl; the compound of formula (Ila) vherein r22 is i-pentyl and r23 is i-pentyl; 20 the compound of formula (Ila) vherein r22 is benzyl and r23 is benzyl. 8. A method for the treatment of virai infections 25 vhich comprises administering to a host in need of such treatment a pharmaceutically effective amount of a compound of Claim 1. 9. A method for the treatment of virai infections 30 vhich comprises administering to a host in need of such treatment a pharmaceutically effective amount of a compound of Claim 2. 35 10. A method for the treatment of virai infections vhich comprises administering to a host in need of such 270 treatment a pharmaceutically effective amount of a compound of Claim 3. 5 11. A method for the treatment of virai infections which comprises administering to a host in need of such treatment a pharmaceutically effective amount of a compound of Claim 4. · 10 12. A method for the treatment of virai infections which comprises administering to a host in need of such treatment a pharmaceutically effective amount of a compound of Claim 5. 15 13. A method for the treatment of virai infections which comprises administering to a host in need of such treatment a pharmaceutically effective amount of a 20 compound of Claim 6. 14. A method for the treatment of virai infections which comprises administering to a host in need of such 25 treatment a pharmaceutically effective amount of a compound of Claim 7. 15. A pharmaceutical composition comprising a 3 0 pharmaceutically acceptable carrier and a pharmaceutically effective antiviral amount of a compound of Claim 1. 16. A pharmaceutical composition comprising a 35 pharmaceutically acceptable carrier and a 271 271 LV 10096 H i * pharmaceutically effective antiviral amount of a compound of Claim 2. 5 17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective antiviral amount of a compound of Claim 3. 10 18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective antiviral amount of a compound of Claim 4. 15 19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective antiviral amount of a 20 compound of Claim 5. 20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a 25 pharmaceutically effective antiviral amount of a compound of Claim 6. 21. A pharmaceutical composition comprising a 30 pharmaceutically acceptable carrier and a pharmaceutically effective antiviral amount of a compound of Claim 7.

Claims (21)

EN 10096 Claims of the Formula Compounds of the Formula (I) and fractions suitable for their pharmaceutical brands, or therapeutic formulations of formula (I): R 7 and R 7 are independently selected from the group consisting of: hydrogen; 11 C 1-6 alkyl substituted with 0-3 R; 11 C2-8 alkenyl substituted with 0-3 R; 11 C 2-8 alkynyl substituted with 0-3 R; C8-8-cycloalkyl substituted with 0-3 R ^; 11C-cycloalkyl substituted with 0-3 R; 0 " lU 12 12 2. aryl substituted with 0-3 R; A C 1-4 carboalkyl group substituted with 0-3 R; 12-0-2 R-substituted heterocyclic ring system containing 5-10 atoms, at least one of which is nitrogen, oxygen or sulfur; 4A 7A R and R are independently taken from the group: hydrogen; C 1-4 alkyl substituted with halogen or C 1-4 alkoxy; benzyl substituted with halogen or C 1-6 alkoxy; forming a 5-7 membered carbocycle, 4 4A R and R may also be bonded to 12 substituted with 0-2 R; forming a 5-7 membered carbocycle, 7 7A R and R may also be linked 12 substituted with 0-2 R; n is 0, 1 or 2; 5 n R is F, F 2, = O, C 1-4 alkyl or -R; 6,2 R when n = 1 is H, = O, F, F 1, C 1-3 alkyl or -OR; R6 when n = 2 is, independently of one another, H, O, F, F, 21, C1-3 alkyl or -OR; 3 EN 10096 R '' and R 'may be bonded to form an epoxy ring; 20 21 R and R are independently taken from the group: hydrogen; C 1-6 alkyl substituted with 0-3 R 10; 1-O 11 C 3-8 alkoxyalkyl substituted with 0-3 R; 11 C, -alkylcarbonyl substituted with 0-3 R; 1- o C, -alkoxycarbonyl substituted with 0-3 R **; lO-12 benzoyl substituted with 0-3 R; 12 phenoxycarbonyl substituted with 0-3 R; 12 phenylaminocarbonyl substituted with 0-3 R; or any group that converts into a mammalian hydroxyl group; R ** taken from one or more of the following groups: 13 14 13 ketogroup, halogen, cyano, -NR R, -C 00 R, -OC (= O) R 13, -OR 13, O, -alkoxyalkyl, -S (0) R13, Z-, -NHC (= NH) NHR13, -C (= NH) NHR13, -C (= O) NR13R14, -NR14C (= O) R13, 1414141314131314 = NOR, -NR C (= O) 0R10C (= O) NRR, -NR C (= O) NRR, 14131414131314 -NRA * SO2NRR, -NRA * SO2R, -SO2, C1-4alkyl , C '- alkenyl, C 1-6 cycloalkyl, C' - cycloalkylmethyl - Z - 4 'o In the group; 1-3 amino acids linked to amide bonds attached to R 7 and R 7 with an amine or carboxyl terminus; 12 C 8 -C 4 carbocyclic substituted with 0-3 R; 12 aryl substituted with 0-3 R; 12 with a 0-2 R R-substituted heterocyclic ring system containing 12 1 5-10 atoms, at least one of which is nitrogen, oxygen or sulfur; · R when it is at the carbon atom taken from one or more of the following groups: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1-6 alkyl, C 3 -C 8 cycloalkyl , C 1-4 cycloalkylmethyl, 13 14 C 1-10 alkylaryl, C 1-4 alkoxy, -NR R 2, C 2-8 alkoxyalkyl, C 1-4 hydroxyalkyl, methylenedioxy grur, ethylenedioxy, C 1-4 haloalkyl, C 1-4 haloalkyl; C1-6 haloalkoxy, C1-4alkoxycarbonyl, C1-6alkylcarbonyloxy, 13C1-6alkylcarbonyl, C1-6alkylcarbonylamino, -SfO1R, R02, NR13R14, -NHSO2R14, -OCH2C00H, 2 - (1-morpholino) ethoxy; 5-6 membered heterocycle containing 1-4 heteroatoms from the group: oxygen, nitrogen, sulfur; 12 R may also have a chain of 3-4 carbon atoms attached to adjacent ring carbon atoms to form a fused 5 or 6 membered ring which may be optionally substituted with aliphatic carbon atoms with halogen, C 1-4 alkyl, C 1-4 alkyl; -al-13 14 -carbyl, hydroxy, -NR R; 12 or in the case of carbonyl and thiocarbonyl when R is attached to a saturated carbon atom; 12 R at the nitrogen atom taken from one or more of the following groups: phenyl, benzyl, phenethyl, hydroxy, v. * C 1-6 alkyl, C 1-6 cycloalkyl, C 3-6 cycloalkylmethyl, 13 14 - NR R, C 2-8 -alkoxyalkyl, C 1-4 -hydroxyalkyl, C 1-6 -haloalkyl, C 1-6 -alkoxycarbonyl, C 1-4 -alkylcarbonyl, C 1-4 -alkylcarbonyloxy; C 1-4 -alkoxy, · 13 R is hydrogen, phenyl, benzyl, C 1-4 -alkyl; 14 R is hydrogen, C 1 -C 6 alkyl; 13 14 R and R can also be connected to form - (CH ") .-, - (CH«) r-, 6 4 L · l > -CH 2 CH 2 N (R 15) CH 2 CH 2 -, -CH 2 CH 2 OCH 2 CH 2 -; R13 is hydrogen, methyl; m is 0, 1 or 2; W is taken from the group: -N (R22) C (= Z) N (R23) -; -N (R 22) S (= O) N (R 23) -; -0C (= Z) 0-; -N (R22) C (= Z) 0-; -C (R25) (R26) C (= Z) C (R27) (R28) -; -N (R 22) C (= Z) C (R 27) (R 28) -; < -C (R25) (R26) C (= Z) 0-; -N (R 22) C (= O) C (= O) N (R 23) -; / -NCR 25) (R 26) CF 2 C (R 27) (R 28) -; -C (R 25) (R 26) N (OR 29) C (R 27) (R 28) -; -C (R25) (R26) C (= Z) S-; wherein: Z is 0, S or NR 24; '22 23 R and R are independently selected from the group: hydrogen; C 1-6 -alkyl substituted with 0-3 R **; 11 C2-8 alkenyl substituted with 0-3 R; C 2-8 alkynyl substituted with 0-3 R **; 11 C2-8-cycloalkyl substituted with 0-3 R; 11 C, -bicycloalkyl substituted with 0-3 R; 0 '1U 12 aryl substituted with 0-3 R; A 12 C 8 -C 4 carboalkyl group substituted with 0-3 R; 12 to 0-2 R substituted heterocyclic ring system containing 5 to 10 atoms, of which at least one is nitrogen, oxygen or sulfur; 24 R is taken from the group: hydroxyl; amino; C1-6alkyl; C 1 -C 10 alkoxy; C1-6 aminoalkyl; 25 27 R and R independently taken from the group: hydrogen; C.n-alkyl substituted with 0-3 R11; LV 10096 C 2-8 alkenyl substituted with 0-3 R 11; 11 C 2-8 alkynyl substituted with 0-3 R; C 1-6 cycloalkyl substituted with 0-3 R **; Cg10-cycloalkylalkyl substituted with 0-3 R **; 12 aryl substituted with 0-3 R; 12 C8-6carboalkyl substituted with 0-3R; 12-0-2 R-substituted heterocyclic ring system containing 5-10 atoms, at least one of which is nitrogen, oxygen or sulfur; 26 28 R and R are independently taken from the group: hydrogen; C 1-4 -alkyl substituted with halogen or C 1-4 -alkoxy or C 1-2 -alkoxy substituted with halogen or C 1-4 -alkoxy substituted benzyl; 29 R selected from the group: hydrogen; C 1-4 alkyl substituted by halogen or C 1-2 alkoxy; with halogen atom or C1-2 "alkyloxy substituted benzyl group 22 25 26 or, R, R and R independently of one another 4 4A with R or R to form 5 or 6 membered fused aromatic or 12 alicyclic heterocycles substituted with 0-2 R; 23 27 28 or, R, R and R, independently of one another, may be joined to 7 7A by R or R to form a 5 or 6 membered fused aromatic or 12 alicyclic heterocycle substituted with 0-2 R; provided that: 4 7 when R is hydrogen, then R is not hydrogen; 4 7 when W is -OC (= Z) 0-, then R and R are not hydrogen; if R 1 is hydrogen, then at least one of these substituents V is not hydrogen: R 22, R 22, R 22, R 2, R 27 n R 4. 2. A compound of claim 1 having the formula (I) or a salt suitable for pharmaceutical purposes, or a prodrug form, wherein: 4 7 · R and R are independently selected from the group consisting of: hydrogen; 11 C 1-4 alkyl substituted with 0-3 R; C 1-4 alkenyl substituted with 0-3 R 4; C3-4alkynyl substituted with 0-3 R11; R4A and R7A are hydrogen; n is 0 or 1; 5 20 R is taken from the group: F, F 2, = O, -R; 6 21 R is taken from the group: H, F, F2, = 0, -OR; 20 21 R and R, independently of one another, are taken from the group: * LV 10096 hydrogen; C 1-8 alkoxycarbonyl; C 1-6 alkylcarbonyl; benzoyl; any group that becomes a free hydroxyl group in a mammal; taken from one or more of the following groups: 13 14 13 ketogroup, halogen, cyano, -NR R, -C 00 R, -CO (= O) R 1, -OR * ^, C 0 -alkoxyalkyl, -S (O) R 1 C 1-6 -alkyl, C 1-4 -alkenyl, C 3-6 -cycloalkyl; A 12-C 1-6 -carbo-cyclic group substituted with 0-3 R; 12 aryl substituted with 0-3 R; 12-0-2 R-substituted heterocyclic ring system containing 5-10 atoms, at least one of which is nitrogen, oxygen or sulfur; 12 R at the carbon atom, taken from the group consisting of phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkylmethyl, 13 14 C7-10-arylalkyl, C1-6alkoxy, -NRR, C0-alkoxyalkyl, C-hydroxyalkyl, methylenedioxy, ethylenedioxy, C1-4 haloalkyl, C1-6 haloalkoxy, C1-4alkoxycarbonyl, C1-4alkylcarbonyloxy , 13 C 1-4 alkylcarbonyl, C 1-4 alkylcarbonylamino, -S (O) m R 12 -SO 2 NR 13 R 14, -NHSO 2 R 14; 5-6 membered heterocycle containing 1-4 heteroatoms from the group: oxygen, nitrogen, sulfur; R can also be a chain of 3-4 carbon atoms attached to adjacent ring carbon atoms to form a fused 5 or 6 membered ring, which may be optionally substituted with aliphatic carbon atoms with halogen, C 1-4 alkyl, C 1-4 -. alpha-13 14 -carbyl, hydroxy, -NR R; 12 or carbonyl and thiocarbonyl when R is attached to a saturated carbon atom; 12 R at the nitrogen atom taken from one or more of the following groups: phenyl, benzyl, phenethyl, hydroxy, N-alkyl, C 1-4 -cycloalkyl, C 36 -cycloalkylmethyl, 13 14 -NR R, C 26 -alkoxyalkyl, C 1-4 hydroxyalkyl, C 1-4 haloalkyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyl, C 1-4 alkylcarbonyloxy; C ^ _4oks alkoxy? 13 R is hydrogen, C 1-8 alkyl; 14 R is hydrogen, (1-4C) alkyl, benzyl; 13 14 R and R may also be joined to form - (CH 2 -, - (CH 2 g-, -CH 2 CH 2 N (R 15) CH 2 CH 2 -, -CH 2 CH 2 OCH 2 CH 2 -; Η LV 10096 1-5 R is hydrogen, methyl; is 0, 1 or 2; W is taken from the group: -N (R) C (= Z) N (R) -; -N (R 22) C (= Z) 0-; -C (R 25) (R 26) C (= Z) C (R27) (R28) -; -N (R22) C (= Z) C (R27) (R28) -; -C (R25) (R26) C (= Z) 0-; N (R22) C (= O) C (= O) N (R23) -; -N (R25) (R26) CF2C (R27) CR28) - wherein: Z is 0; the other selected from the group: hydrogen; 11 C 1-8 alkyl substituted with 0-3 R 11 C 2-8 alkenyl substituted with 0-3 R 11 C 2-8 alkynyl substituted with 0-3 R 11; C8-8-cycloalkyl substituted with 0-3 R; 25-27 R and R independently taken from the group: hydrogen; 11C-alkyl substituted with 0-3 R; 1'-C-alkenyl substituted with 0-3 R *; c # 0-O-alkynyl substituted with 0-3 R 10 O 26 28 R and R is hydrogen, provided that: 4 7 when R is hydrogen the rhine atom, then R is not hydrogen; 4 7 when W is -OC (= Z) 0-, then R and R are not hydrogen; 4 If R is hydrogen then at least one of these substituents _. * 4. b22 d23 d23 “26 _.27 n28 is not hydrogen: R, R, R, R, R and R. 3. A compound of claim 1 having the formula (II) (II) or a pharmaceutically acceptable salt thereof, or a prodrug, wherein: 4 7 R and R are independently selected from the group: hydrogen; 11 C 1-6 alkyl substituted with 0-3 R; C 1-4 alkenyl substituted with 0-3 R 1 -; 20 R is -R 1 R 4 and H or -R 1 R *; ο LV 10096? Q 21 κ and R independently taken from the group: hydrogen; or any group that converts to a hydroxyl group in a mammal; 11 R is taken from one or more of the following groups: 13 14 13 ketogroup, halogen, -NR R, -R 1, C 2-4 alkoxyalkyl, C 1-4 alkyl, C 1-4 alkenyl, C 1-4 cycloalkyl, 12 aryl substituted with 0-3 R; 12 with a 0 - 2 R substituted heterocyclic ring system containing 5-10 atoms, at least one of which is nitrogen, oxygen or serum; 12 R at the carbon atom taken from the following groups: phenyl, benzyl, phenethyl, halogen, 13 14 C 1-6 alkyl, C 1-4 alkoxy, -NR R, phenoxy, methylenedioxy, C 1-6 haloalkyl a group, a benzyloxy group, a C 7 -C 10 aralkyl group, a C 1-4 alkylcarbonyl group, a C 1-6 alkylcarbonylamino group; 5-6 membered heterocycle containing 1-4 heteroatoms from the group: oxygen, nitrogen, sulfur; 12 R when it is at the nitrogen atom is benzyl or methyl; 13 R is hydrogen, C 1-6 alkyl; 14H is hydrogen, C1-2 alkyl; R13 and R14 may also be joined to form -CH2CH2N (R15) CH2CH2-, -CH2CH20CH2CH2-; W is taken from the group: -N (R22) C (= 2) N (R23) -; -C (R25) (R26) C (= Z) C (R27) (R28) -; -N (R 22) C (= Z) C (R 27) (R 28) -; -C (R25) (R26) C (= Z) 0-; wherein: Z is 0; 22 23 R and R are independently selected from the group: hydrogen; C1-6 alkyl substituted with 0-3 R1; 11 C 1-4 alkenyl substituted with 0-3 R; 25 27 R and R independently taken from the group: hydrogen; C1-6 alkyl substituted with 0-3 R1; 11 C 1-4 alkenyl substituted with 0-3 R; 26 28 R and R are hydrogen; provided that: 4 7 when R is hydrogen, then R is not hydrogen; 4 if R is hydrogen, at least one of these substituents 1 is not hydrogen: R, R, R, R, R and R. A compound according to claim 3 wherein: 4 7 R and R are independently selected from the group: hydrogen; C1-6alkyl substituted with 0-3 R **; R5 is -OR20; R 1 is H or -OR 2 *; 20 21 R and R are independently taken from the group: hydrogen; or any group that converts into a mammalian hydroxyl group; R 1 * is taken from one or more of the following groups: 13 halogen, -RR, C 1-4 alkyl, C 1-4 cycloalkyl, 12 aryl substituted with 0-2 R; heterocyclic system of the group: pyridine, pyrimidine, triazine, furan, thiophene, pyrrole, pyrazole, imidazole, tetrazole, benzofuran, indole, quinoline. isoquinoline; 12 R when attached to a carbon atom, taken from the following groups: halogen, N-alkoxy, benzyloxy, -CF 1, methyl, 2- (1-morpholino) ethoxy; 12 R when it is at the nitrogen atom is methyl; 13 R is hydrogen or methyl; 14 R is hydrogen or methyl; R * 3 and R 4 may also be joined to form - (C 1-4) -CH 2 CH 2 N (R 15) CH 2 CH 2 -, -CH 2 CH 2 OCH 2 CH 2 -; W is -N (R 22) C (= O) N (R 23) -; where: 22 23 R and R are independently selected from the group: hydrogen; C 1-4 alkyl substituted with 0-3 R 1; C 2-8 alkenyl substituted with 0-3 R **; provided that: 4 7 when R is hydrogen, then R is not hydrogen; 4 22 23 if R is hydrogen, then at least one of R or R is not hydrogen. A compound of claim 1 having the formula (IIa) O (ila) taken from the group: 22 23 compound (IIa) wherein R is H, R is H; Compound 23 (IIa) wherein R is allyl, R is allyl; Compound (IIa) wherein R is 3,7-dimethyl-1-octyl, R23 is 3,7-dimethyl-1-octyl; Compound 22 (IIa) wherein R is -CH2CH2OCH2CH2OCH3, R23 is -CH2CH2OCH2CH2OCH3; 22 23 compound (IIa), wherein R is 3,7-dimethyl-1-octyl, R is H 2? A 2T compound (IIa) wherein R is - (CH2CH2O) 30CH3, R is H; Compound 22 (IIa) wherein R is - (CH2CH2O) 3CH3, R23 is - (CH2CH2O) 30CH3; Compound 22 (IIa) wherein R is -CH2 CH2 OH, R23 is -CH2CH2NHCH [CH (CH3) 21-C00-CH2C6H5; 2? a compound (IIa) wherein R is -CHOCHoNHCH [CH (CH2) o] -C00-CH2C6Hc, £ Z ό ΔZo5 23R is -CH2CH2NHCH1CH (CH3) 2) -C00-CH2C6H5; A compound of formula (IIa) wherein R is propyl, R is propyl; A compound of formula (IIa) wherein R is methyl, R is methyl; Compound 22 (IIa) wherein R is cyclopropylmethyl, 23 R is cyclopropylmethyl; Compound 22 (IIa) wherein R is n-hexyl, 23 R is n-hexyl; Compound 22 (IIa) wherein R is n-butyl, 23 R is n-butyl; Compound 22 (IIa) wherein R is N-morpholinoethyl, 23 R is N-morpholinoethyl; Compound 22 (IIa) wherein R is n-heptyl, R is n-heptyl; η compound (11a) wherein R22 is -CH2CH == CH (CH3) 2, R23 is -CH2CH = CH (CH3) 2; compound (11a) wherein R is ethyl, 23 R is ethyl; Compound 22 (11a) wherein R is -CH 2 CH = CH (CH 3) 2, R 23 is H; Compound 22 (IIa) wherein -R is isopentyl, 23 R-and isopentyl; Compound 22 (IIa) wherein R is 4-pyridylmethyl, R23 is 4-pyridylmethyl; Compound 22 (IIa) wherein R is 2-methyl, 23 R is 2-methyl; Compound 22 (IIa) having R is n-pentyl, 23 R is n-pentyl; Compound 22 (IIa) R is isooctyl, 23 R is isooctyl; Compound (IIa) having R is isoheptyl, 23 R is isoheptyl; Compound 22 (IIa) wherein R is isohexyl, 23 R is isohexyl; Compound 22 (IIa) wherein R is isobutyl, 23 R is isobutyl; Compound 22 (IIa) wherein R is 3-propargyl, 23 R is 3-propargyl; Compound 22 (IIa) wherein R is benzyl, 23 R is benzyl; Compound 22 (IIa) wherein R is 2-pyridylmethyl, 3 R is 2-pyridylmethyl; Compound 22 (IIa) wherein R is phenylpropyl, 23 R is phenylpropyl; Compound (11a) wherein R is allyl, 23 R is isoprenyl; Compound 22 (IIa). wherein R is 1-cinnamyl, 23 R is 1-cinnamyl. A compound according to claim 1 having the formula (IIa) (IIa) taken from the group: 2223 compound (IIa) wherein R is allyl, R is allyl; A compound of formula (IIa) wherein R is propyl, R is propyl; Compound 22 (IIa) wherein R is cyclopropylmethyl, 23 R is cyclopropylmethyl; Compound 22 (IIa) wherein R is n-hexyl, 23 R is n-hexyl; A compound of formula (IIa) wherein R is n-butyl, R is n-butyl; compound (IIa) wherein R22 is -CH2CH = C (CH3) 2, R23 is -CH2CH = C (CH3) 2; compound (IIa) wherein R22 is -CH2CH2CH (CH3) 2, R23 is H; Compound (IIa) wherein R is isopentyl, 23 R is isopentyl; Το compound (IIa) wherein R is 2-methyl, 23 R is 2-methyl; Compound 22 (IIa) wherein R is n-pentyl, 23 R is n-pentyl; Compound 22 (IIa) wherein R is isohexyl, 23 R is isohexyl; Compound 22 (IIa) wherein R is 1-cinnamyl, 23 R is i-cinnamyl; Compound 22 (IIa) wherein R is benzyl, R is benzyl; Compound (IIa) wherein R is allyl, R is isoprenyl. 7. A compound of claim 1 having the formula (IIa) (IIa) taken from the group: po po compound (IIa) wherein R is allyl, R is allyl; Compound 22 (IIa) wherein R is cyclopropylmethyl, 23 R is cyclopropylmethyl; A compound of formula (IIa) wherein R is n-butyl, R is n-butyl; compound (IIa) wherein R22 is -CH2CH = C (CH3) 2, R23 is -CH2CH = C (CH3) 2; I * EN 10096 22 23 compound (IIa) wherein R is propyl, R is propyl; Compound 22 (IIa) having R isopentyl, 23 R is isopentyl; 22 23 (IIa) wherein R is benzyl, R is benzyl. A method of treating a viral infection, characterized in that a therapeutically effective amount of the compound is administered to the infected subject according to claim 1. A method of treating a viral infection, characterized in that a therapeutically effective amount of a compound of claim 2 is administered to the infected. 10. A method of treating a viral infection, characterized in that a therapeutically effective amount of a compound of claim 3 is administered to the infected. A method of treating a viral infection, characterized in that. administering a therapeutically effective amount of the compound of claim 4 to the infected. 12. Ε®2® {2122§ for the treatment of a viral infection, characterized in that a therapeutically effective amount of the compound is administered to the infected subject according to claim 5. (13.? 22?! 5? ® 2 :: for the treatment of a viral infection, characterized in that the infectious agent is administered a 2-L effective amount of the compound of claim 6. A method of treating a viral infection, characterized in that a therapeutically effective amount of a compound of claim 7 is administered to the infected. 15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1. 16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 3. 18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 4. 19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 5. 20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 6. 21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 7.