IP Library › Granted Patent US 8,318,748

Granted Patent B2

US 8,318,748 · App. 13/115,462 · Granted Nov 27, 2012

Cathepsin cysteine protease inhibitors

Assignees: Merck, Sharp & Dohme Corp.; Axys Pharmaceuticals, Inc.

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Quick Facts

Patent No.: US 8,318,748
App. No.: 13/115,462
Granted: Nov 27, 2012
Kind: B2

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Abstract

This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

Claims (647)

1. A method of treating osteoporosis in a mammal in need thereof by administering to the mammal a therapeutically effective amount of a compound of the following chemical formula:

wherein R 1 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C 3-6 cycloalkyl, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —OR 9 , —N(R 12 ) 2 , aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;

R 2 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C 3-6 cycloalkyl, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —OR 9 , —N(R 12 ) 2 , aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;

or R 1 and R 2 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl or heterocyclyl ring wherein said ring system is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, hydroxyalkyl, haloalkyl, or halo;

R 3 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C 3-6 cycloalkyl or one to six halo;

R 4 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C 3-6 cycloalkyl or one to six halo;

or R 3 and R 4 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl ring, C 5-8 cycloalkenyl ring, or five to seven membered heterocyclyl wherein said cycloalkyl, cycloalkenyl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;

R 5 is selected from hydrogen or C 1-6 alkyl substituted with 1-6 halo;

R 6 is aryl, heteroaryl, C 1-6 haloalkyl, arylalkyl or heteroarylalkyl, wherein said aryl, heteroaryl, arylalkyl and heteroarylalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, haloalkoxy, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —N(R 10 )(R 11 ), cyano, or aryl which is optionally substituted with —SO 2 R 12 ;

each D is independently C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, aryl, heteroaryl, C 3-8 cycloalkyl or heterocyclyl wherein each said aryl, heteroaryl, cycloalkyl and heterocyclyl groups, which may be monocyclic or bicyclic, is optionally substituted on either the carbon or the heteroatom with one to five substituents independently selected from C 1-6 alkyl, haloalkyl, halo, keto, alkoxy, —SR 9 , —SR 12 , —OR 9 , —OR 12 , N(R 12 ) 2 , —SO 2 R 9 , or —SO 2 R 10 ;

R 7 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkyloxy, halo, nitro, cyano, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, —C(O)OR 10 , —C(O)OSi[CH(CH 3 ) 2 ] 3 , —OR 9 , —OR 10 , —C(O)R 10 , —R 10 C(O)R 9 , —C(O)R 9 , —C(O)N(R a )(R b ), —C(O)N(R 12 )(R 12 ), —C(O)N(R 10 )(R 11 ), —C(R 10 )(R 11 )OH, —SR 12 , —SR 9 , —R 10 SR 9 , —R 9 , —C(R 9 ) 3 , —C(R 10 )(R 11 )N(R 9 ) 2 , —NR 10 C(O)NR 10 S(O) 2 R 9 , —SO 2 R 12 , —SO(R 12 ), —SO 2 R 9 , —SO m N(R c )(R d ), —SO m CH(R 10 )(R 11 ), —SO 2 N(R 10 )C(O)(R 12 ), —SO 2 (R 10 )C(O)N(R 12 ) 2 , —OSO 2 R 10 , —N(R 10 )(R 11 ), —N(R 10 )C(O)N(R 10 )(R 9 ), N(R 10 )CO(R 9 ), —N(R 10 )C(O)R 10 , —N(R 10 )C(O)OR 10 , —N(R 10 )SO 2 (R 10 ), —C(R 10 )(R 11 )NR 10 C(R 10 )(R 11 )R 9 , —C(R 10 )(R 11 )N(R 10 )R 9 , —C(R 10 )(R 11 )N(R 10 )(R 11 ), —C(R 10 )(R 11 )SC(R 10 )(R 11 )(R 9 ), R 10 S—, —C(R a )(R b )NR a C(R a )(R b )(R 9 ), —C(R a )(R b )N(R a )(R b ), —C(R a )(R b )C(R a )(R b )N(R a )(R b ), —C(O)C(R a )(R b )N(R a )(R b ), —C(R a )(R b )N(R a )C(O)R 9 , —C(O)C(R a )(R b )S(R a ), C(R a )(R b )C(O)N(R a )(R b ), —B(OH) 2 , —OCH 2 O— or 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl;

wherein said groups are optionally substituted on either the carbon or the heteroatom with one to five substituents independently selected from C 1-6 alkyl, halo, keto, cyano, haloalkyl, hydroxyalkyl, —OR 9 , —NO 2 , —NH 2 , —NHS(O) 2 R 8 , —R 9 SO 2 R 12 , —SO 2 R 12 , —SO(R 12 ), —SR 12 , —SR 9 , —SO m N(R c )(R d ), —SO m N(R 10 )C(O)(R 12 ), —C(R 10 )(R 11 )N(R 10 )(R 11 ), —C(R 10 )(R 11 )OH, —COOH, —C(R a )(R b )C(O)N(R a )(R b ), —C(O)(R a )(R b ), —N(R 10 )C(R 10 )(R 11 )(R 9 ), —N(R 10 )CO(R 9 ), —NH(CH 2 ) 2 OH, —NHC(O)OR 10 , —Si(CH 3 ) 3 , heterocycyl, aryl or heteroaryl;

R 8 is hydrogen or C 1-6 alkyl;

or R 4 and R 8 or can be taken together with any of the atoms to which they may be attached or are between them to form a 4-10 membered heterocyclyl ring system wherein said ring system, which may be monocyclic or bicyclic, is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, keto, —OR 10 , —SR 10 or —N(R 10 ) 2 ;

R 9 is selected from the group consisting of hydrogen, aryl, aryl(C 1-4 )alkyl, heteroaryl, heteroaryl(C 1-4 )alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl(C 1-4 )alkyl, and heterocyclyl(C 1-4 )alkyl wherein said groups can be optionally substituted with one, two, or three substituents independently selected from halo, alkoxy or —SO 2 R 12 ;

R 10 is hydrogen or C 1-6 alkyl

R 11 is hydrogen or C 1-6 alkyl;

R 12 is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo, alkoxy, cyano, —NR 10 or —SR 10 ;

R a is hydrogen, C 1-6 alkyl, (C 1-6 alkyl)aryl, (C 1-6 alkyl)hydroxyl, —O(C 1-6 alkyl), hydroxyl, halo, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, wherein said alkyl, aryl, heteroaryl, C 3-8 cycloalkyl and heterocyclyl can be optionally substituted on either the carbon or the heteroatom with one, two, or three substituents independently selected from C 1-6 alkyl or halo;

R b is hydrogen, C 1-6 alkyl, (C 1-6 alkyl)aryl, (C 1-6 alkyl)hydroxyl, alkoxyl, hydroxyl, halo, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, wherein said alkyl, aryl, heteroaryl, C 3-8 cycloalkyl and heterocyclyl can be optionally substituted on either the carbon or the heteroatom with one, two, or three substituents independently selected from C 1-6 alkyl or halo;

or R a and R b can be taken together with the carbon atom to which they are attached or are between them to form a C 3-8 cycloalkyl ring or C 3-8 heterocyclyl ring wherein said 3-8 membered ring system may be optionally substituted with one or two substituents independently selected from C 1-6 alkyl and halo;

R c is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo or —OR 9 ;

R d is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo or —OR 9 ;

or R c and R d can be taken together with the nitrogen atom to which they are attached or are between them to form a C 3-8 heterocyclyl ring which is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, halo hydroxyalkyl, hydroxy, alkoxy or keto;

n is independently selected from an integer from one to three;

each m is independently selected from an integer from zero to two;

and the pharmaceutically acceptable salts and stereoisomers thereof.

2. The method of claim 1 wherein R 1 is hydrogen and R 2 is hydrogen, or R 1 and R 2 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl ring wherein said ring system is optionally substituted with one or two substituents selected from C 1-6 alkyl or halo, and the pharmaceutically acceptable salts and stereoisomers thereof.

3. The method of claim 2 wherein R 3 is C 1-6 alkyl which is optionally substituted with one to six halo and R 4 is hydrogen, and the pharmaceutically acceptable salts and stereoisomers thereof.

4. The method of claim 3 wherein R 3 is n-propyl, isobutyl, 2-fluoro-2-methylpropyl, 2-trifluoromethylpropyl, 3-fluoro-2-(2-fluoromethyl)propyl, 2,2-difluoroethyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, or 2,2-dichloroethyl and R 4 is hydrogen; and the pharmaceutically acceptable salts and stereoisomers thereof.

5. The method of claim 3 wherein R 5 is hydrogen and R 6 is aryl or heteroaryl wherein said aryl or heteroaryl are optionally substituted with one, two or three substituents selected from halo or —SO 2 R 12 ; and the pharmaceutically acceptable salts and stereoisomers thereof.

6. The method of claim 3 wherein R 5 is hydrogen and R 6 is C 1-6 haloalkyl; and the pharmaceutically acceptable salts and stereoisomers thereof.

7. The method of claim 6 wherein R 5 is hydrogen and R 6 is trifluoromethyl or 3,3,3,2,2-pentafluoroethyl; and the pharmaceutically acceptable salts and stereoisomers thereof.

8. The method of claim 6 wherein n is two, each D is independently aryl or heteroaryl and R 7 is —SO m CH(R 10 )(R 11 ) or —SO m (R c )(R d ), R c and R d are each independently hydrogen or C 1-6 alkyl; and the pharmaceutically acceptable salts and stereoisomers thereof.

9. The method of claim 1 wherein the compound is selected from:

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-phenylethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-fluoro-3-methylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-{[4-(2-fluoroethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-fluoroethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;

N 2 -[1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(3-hydroxy-3-methylbut-1-ynyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-hydroxy-3-methylbutyl)phenyl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4-pyridin-4-ylphenyl)propyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(1E)-3-hydroxy-3-methylbut-1-enyl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxidopyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(morpholin-4-ylcarbonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{[methoxy(methyl)amino]carbonyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-thien-3-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(hydroxymethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-cyano-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-difluoro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;

4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-2-carboxylic acid methyl ester;

4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-3-carboxylic acid methyl ester;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-dimethoxy-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(trifluoromethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-dichloro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-formyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)phenyl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[4-(5-bromopyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-indol-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-5-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-3-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid methyl ester;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-2-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-furyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[3-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[4-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 2 -{(1S)-1-[4′-(acetylamino)-3′-fluoro-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methylthien-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 2 -{(1S)-1-[4-(5-acetylthien-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(trifluoromethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5′-fluoro-2′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,5′-difluoro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′,3′,5′-trifluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

3-(4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-3-yl)-acrylic acid;

N 2 -{(1S)-1-[4-(9-anthryl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(4′-benzoyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(3′-acetyl-4′-hydroxy-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-1-[2′-(cyanomethyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-morpholin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(5-phenylthien-2-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-quinolin-8-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-2-ylphenyl)ethyl]-L-leucinamide;

N 2 -{1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(morpholin-4-ylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(isopropylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -((1S)-1-{4′-[(acetylamino)sulfonyl]-1,1′-biphenyl-4-yl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[1-(5-bromothien-2-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

4-(4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-yl)-piperazine-1-carboxylic acid tert-butyl ester;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-hydroxyethyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(1-{4-[(dimethylamino)carbonyl]phenyl}-2,2,2-trifluoroethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(1-{4-[(cyclopropylamino)carbonyl]phenyl}-2,2,2-trifluoroethyl)-L-leucinamide;

4-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-benzoic acid;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-fluoroethyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-thiazol-4-yl)phenyl]ethyl}-L-leucinamide;

N 2 -{1-[4-(3-tert-butyl-1,2,4-triazin-5-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{2-[3-(methylsulfonyl)phenyl]-1,3-thiazol-4-yl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[2-(1H-pyrazol-4-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(methylsulfonyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 2 -[1-(3-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-3-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(3-pyridin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-3-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-3-yl]ethyl}-L-leucinamide;

N-(cyanomethyl)-1-[(2,2,2-trifluoro-1-phenylethyl)amino]cyclohexanecarboxamide;

1-{[1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-N-(cyanomethyl)cyclohexanecarboxamide;

N-(cyanomethyl)-1-{[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]amino}cyclohexanecarboxamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-piperidin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(4-pyridin-2-ylpiperazin-1-yl)phenyl]ethyl}-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-3-cyclopropylalaninamide;

N 1 -(cyanomethyl)-3-cyclopropyl-N 2 -[2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]alaninamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-pyridin-4-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(1,3-thiazol-2-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-methoxyphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-pyridin-4-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-phenoxyphenyl)ethyl]-L-leucinamide;

N 2 [(1S)-1-(4′-bromo-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{(1S)-1-[4-(4-chloropyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{(1S)-1-[4′-(acetylamino)-2′-methyl-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4″-(methylsulfonyl)-1,1′:4′,1″-terphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-L-alaninamide;

N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;

N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 2 [(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(hydroxymethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-D-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-D-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(morpholin-4-ylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-D-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[(methylamino)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-D-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4-(1-oxidopyridin-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(1-oxidopyridin-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[6-(1-hydroxy-1-methylethyl)-1-oxidopyridin-3-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-piperazin-1-ylphenyl)ethyl]-L-leucinamide;

N 2 -{1-[3′-(acetylamino)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(4-propylpiperazin-1-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(piperazin-1-ylcarbonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}phenyl)ethyl]-L-leucinamide;

4-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-benzoic acid methyl ester;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(E)-2-quinolin-2-ylethenyl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]ethyl}-L-leucinamide;

N 2 -((1S)-1-{4-[3-(5-bromopyridin-3-yl)-1,2,4-oxadiazol-5-yl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(4-benzoylphenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(thien-2-ylcarbonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-ylcarbonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{(Z)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{(E)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-isobutyrylphenyl)ethyl]-L-leucinamide;

N 2 -{(1S)-1-[4-(4-bromo-1,3-thiazol-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-cyanophenyl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-ethynylphenyl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(2-methylquinolin-7-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(1H-indol-5-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{1-[4′-(dimethylamino)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-{[(cyanomethyl)amino]carbonyl}phenyl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1R)-1-(4-{[(cyanomethyl)amino]carbonyl}phenyl)-2,2,2-trifluoroethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid;

4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid methoxy-methyl-amide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-({[4-(methylsulfonyl)benzyl]thio}methyl)phenyl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[4-(5-chloropyridin-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{(1S)-1-[3′-(aminosulfonyl)-4′-bromo-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{(1S)-1-[4′-bromo-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-methyl-6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;

N 2 -[(1S)-1-(4-{5-chloro-3-[4-(methylsulfonyl)phenyl]pyridin-2-yl}phenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(phenylthio)methyl]phenyl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(trifluoromethyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{[(4-fluorobenzoyl)amino]methyl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(methylsulfonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 2 -((1S)-1-{4-[({[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)methyl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -((1S)-1-{4-[(9-chloro-3-methyl-4-oxoisoxazolo[4,3-c]quinolin-5(4H)-yl)methyl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[4″-chloro-4′-(methylsulfonyl)-1,1′:2′,1″-terphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methoxy-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[2′-chloro-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxyethyl)thio]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-fluoro-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxyethyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-({2-[methoxy(methyl)amino]-2-oxoethyl}sulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(4-bromophenyl)(2,4,6-trifluorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(4-pyridin-4-ylphenyl)(2,4,6-trifluorophenyl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[[4-(4-fluorobenzyl)phenyl](phenyl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{phenyl[4-(pyridin-3-ylmethyl)phenyl]methyl}-L-leucinamide;

N 2 -{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{[4-(methylsulfonyl)phenyl][4′-(methylthio)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(methylsulfonyl)phenyl]methyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2,2,2-trichloro-1-(4-glycoloylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[2-fluoro-1-(fluoromethyl)-1-phenylethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(pyrrolidin-1-ylacetyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(piperazin-1-ylcarbonyl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-3-(1-methylcyclopropyl)-N 2 -(2,2,2-trifluoro-1-{4-[1-(2-hydroxyethyl)prolyl]phenyl}ethyl)-L-alaninamide;

N 2 -[[4-(4-tert-butylpiperazin-1-yl)phenyl](pentafluorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N-(cyanomethyl)-1-{1-[4-(4-methylpiperazin-1-yl)phenyl]ethyl}piperidine-2-carboxamide;

N 2 -[[4-(4-tert-butylpiperazin-1-yl)phenyl](pyridin-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -{[4-(4-tert-butylpiperazin-1-yl)phenyl][5-(trifluoromethyl)pyridin-2-yl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;

(4S)—N-(cyanomethyl)-4-methyl-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;

(4S)—N-(cyanomethyl)-4-methyl-1-[(1R)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;

N-(cyanomethyl)-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;

N-(cyanomethyl)-1-[(1R)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;

N-(cyanomethyl)-4,4-difluoro-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-methylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-oxazol-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrazin-2-ylphenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-fluoro-4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(1-hydroxy-1-methylethyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]propyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 [(1S)-2,2,3,3,3-pentafluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -{(1S)-1-[3′-(aminosulfonyl)-4′-methoxy-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(5-methylpyridin-2-yl)phenyl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 ((1S)-2,2,2-trifluoro-1-{4-[5-(methylsulfonyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[5-(1H-pyrazol-3-yl)pyridin-2-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5-quinolin-5-ylpyridin-2-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5-quinolin-6-ylpyridin-2-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2-difluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,3,3,3-pentafluoropropyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1-ethoxyvinyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-acetylphenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-isopropylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-phenylethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-hydroxy-1-methylethyl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-methylcyclopropyl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′,4′,6′-trimethyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -{(1S)-1-[5-(4-acetylphenyl)pyridin-2-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -{(1S)-1-[6-(4-acetylphenyl)pyridin-3-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -{(1S)-1-[5-(3-acetylphenyl)pyridin-2-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(1-hydroxyethyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -(1-benzyl-2,2,2-trifluoroethyl)-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(1S)-1-(4-tert-butylphenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-4-methyl-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-methyl-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[2-(1H-pyrazol-4-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-thiazol-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -[(1S)-1-cyanoethyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -[(1S)-1-cyano-3-(methylthio)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -[(1S)-1-cyano-3-(methylsulfonyl)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]propyl}-L-leucinamide;

N 2 -[(1S)-1-(5-bromopyridin-2-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(methylsulfonyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(6′-methyl-3,3′-bipyridin-6-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-1,6-dihydropyridin-2-yl)phenyl]ethyl}-L-leucinamide;

(4S)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

(4S)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

(4S)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

(4S)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

(4S)—N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-5,5,5-trifluoro-L-leucinamide;

(4S)—N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide;

N 2 -{(1S)-1-[4-(6-aminopyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methylpyridin-3-yl)phenyl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methylpyridin-3-yl)phenyl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(2,2,2-trifluoro-1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]propyl}-L-leucinamide;

(4R)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

(4R)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(1,3-thiazol-2-yl)phenyl]propyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-1-(4-ethynylphenyl)-2,2,3,3,3-pentafluoropropyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,3,3,3-pentafluoropropyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(4,5-dimethyl-1,3-thiazol-2-yl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-alaninamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,3,3,3-pentafluoropropyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((1S)-2,2,3,3,3-pentafluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}propyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(isopropylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;

N 1 -(1-cyano-1-methylethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(trifluoromethoxy)phenyl]methyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-2-yl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-(4′-piperazin-4-ium-1-yl-1,1′-biphenyl-4-yl)(thien-2-yl)methyl]-L-leucinamide methanesulfonate;

N 1 -(cyanomethyl)-N 2 -{(S)-(4-fluorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(trifluoromethyl)phenyl]methyl}-L-leucinamide;

N 2 -{(S)-(4-chlorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 2 -[(S)-(4-bromophenyl)(thien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl](thien-2-yl)methyl]-L-leucinamide;

N 2 -{(R)-(4-bromophenyl)[4-(trifluoromethoxy)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl][4-(trifluoromethoxy)phenyl]methyl}-L-leucinamide;

N 2 -[(S)-(4-bromophenyl)(2-furyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-2-furyl[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-norvalinamide;

N 2 -{(R)-(4-bromophenyl)[4-(trifluoromethyl)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{1-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-norvalinamide;

N 2 -[(R)-(4-bromophenyl)(4-chlorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 2 -[(S)-(4-bromophenyl)(3-methylthien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(S)-(4-bromophenyl)(thien-3-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-(2,4-difluorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;

N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-5,5,5-trifluoro-L-norvalinamide;

N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 2 -[(S)-(4-bromophenyl)(3-methylthien-2-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -{(S)-3-furyl[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-norvalinamide N 2 -[(S)-(4-bromophenyl)(4-bromothien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 2 -[(S)-(4-bromophenyl)(thien-3-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(cyanomethyl)-N 2 -((S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]{4-[4-(methylsulfonyl)phenyl]thien-2-yl}methyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;

N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-norvalinamide;

N 2 -[(S)-(4-bromophenyl)(4-bromothien-2-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(S)-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 2 -[(S)-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-norvalinamide;

2-{[(4-Bromo-phenyl)-pyridin-4-yl-methyl]-amino}-pentanoic acid cyanomethyl-amide;

2-{[(4-Bromo-phenyl)-thiazol-2-yl-methyl]-amino+}-pentanoic acid cyanomethyl-amide;

(2S)-2-[(S)-1-(4′-Acetylbiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-[(S)-1-(2′,4′-Difluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-[(S)-1-(3′,4′-Difluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-[(S)-1-(3′-Chloro-4′-fluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid(1-cyano-cyclopropyl)-amide;

(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-methanesulfonylamino-biphenyl-4-yl)-ethylamino]-pentanoic acid(1-cyano-cyclopropyl)-amide;

(2S)-2-{(S)-[(4-Bromo-phenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid cyanomethyl-amide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-3′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-2′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

(2S)-2-{(S)-2,2,2-Trifluoro-1-[4-(1H-indol-5-yl)-phenyl]-ethylamino}-pentanoic acid(1-cyano-cyclopropyl)-amide;

(2S)-2-[(S)-2,2,2-Trifluoro-1-(3′-methanesulfonylamino-biphenyl-4-yl)-ethylamino]-pentanoic acid(1-cyano-cyclopropyl)-amide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-fluoro-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-fluoro-3′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-fluoro-4′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-trifluoromethoxy-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-methylbiphenyl-4-yl)-ethylamino]-pentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-[(S)-1-(4′-Cyanobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid(1-cyanocyclopropyl)-amide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(benzo[1,3]dioxol-5-yl)phenyl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methoxycarbonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

(2S)-2-{(S)-[(4-Bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-{(S)-[(4′-Methanesulfonyl-biphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methyl-pentanoic acid cyanomethyl-amide;

(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethylamino]-pentanoic acid(1-cyano-cyclopropyl)-amide;

(2S)-2-[(S)-2,2,2-Trifluoro-1-(2′-trifluoromethyl-biphenyl-4-yl)-ethylamino]-pentanoic acid(1-cyano-cyclopropyl)-amide;

(2S)-2-{(S)-[(2′,4′-Difluorobiphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid(1-cyanocyclopropyl)-amide;

(2S)-2-{(S)-[(4′-Methanesulfonylbiphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid(1-cyanocyclopropyl)-amide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxido-2,3-dihydro-1-benzothien-5-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-2,3-dihydro-1-benzothien-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(cyanomethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

(2S)—N-(cyanomethyl)-4,4-difluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)—N-(1-cyanocyclopropyl)-4,4-difluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)—N-(1-cyanocyclopropyl)-4,4-difluoro-2-({(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)—N-(cyanomethyl)-4,4-difluoro-2-({(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)-4,4-dichloro-N-(cyanomethyl)-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)-4,4-dichloro-N-(1-cyanocyclopropyl)-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)-4,4-dichloro-N-(1-cyanocyclopropyl)-2-({(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

(2S)-4,4-dichloro-N-(cyanomethyl)-2-({(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 2 -[(1S)-1-(2′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(methylsulfonyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{6-[4-(methylsulfonyl)phenyl]pyridin-3-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{6-[(methylsulfonyl)amino]pyridin-3-yl}phenyl)ethyl]-L-leucinamide;

N 1 -(cyanomethyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{6-[(methylsulfonyl)amino]pyridin-3-yl}phenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanobutyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyano-2-cyclopropylethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyano-2-pyridin-3-ylethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyano-3-hydroxy-3-methylbutyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,3-dimethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,3-diethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dimethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-diethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(1,1-dimethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(1,1-diethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(3,3-dimethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(3,3-diethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-2,5-dihydrofuran-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(2,2-dimethyl-5-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4(2,2-diethyl-5-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-oxo-2,5-dihydrofuran-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4(5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4(5,5-diethyl-2-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-4-oxaspiro[2.4]hept-6-en-7-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-5-oxaspiro[3.4]oct-7-en-8-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-4-oxaspiro[2.4]hept-6-en-6-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-5-oxaspiro[3.4]oct-7-en-7-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -[(1S)-1-cyano-3-(methylsulfonyl)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-methyl-6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[6-(1-hydroxy-1-methylethyl)-5-methylpyridin-3-yl]phenyl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylquinolin-7-yl)phenyl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-4,4-difluoro-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1S)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1R)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(trifluoroacetyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[5-(2-naphthyl)pyridin-2-yl]ethyl}-L-leucinamide;

N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;

N 2 -[(4-bromophenyl)(phenyl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 2 -{(1S)-1-[4-(5-chloropyridin-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(methylsulfonyl)amino]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;

N 2 -[(1S)-1-(4-bromophenyl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2-difluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-5-ylphenyl)ethyl]-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;

N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;

N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;