Haloalkyl containing compounds as cysteine protease inhibitors

1. A compound of Formula (I):

R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) cycloalkylene optionally substituted with one or two R b independently selected from alkyl, halo, alkylamino, dialkylamino, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, alkoxycarbonyl, or aryloxycarbonyl or (ii) heterocyclylalkylene optionally substituted with one to four R c which are independently selected from alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkyloxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, aminoalkyl, acyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, cycloalkylalkyl, —S(O) n2 R 14 , -alkylene-S(O) n2 —R 15 , —COOR 16 , -alkylene-COOR 17 , —CONR 18 R 19 , or -alkylene-CONR 20 R 21 (where n2 is 0-2 and R 14 -R 17 , R 18 and R 20 are independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, or heterocyclyl and R 19 and R 21 are independently hydrogen or alkyl) wherein the aromatic or alicyclic ring in the groups attached to cycloalkylene or heterocyclylalkylene is optionally substituted with one, two, or three substituents independently selected from alkyl, haloalkyl, alkoxy, hydroxy, haloalkoxy, halo, carboxy, alkoxycarbonyl, amino, monsubstituted amino, disubstituted amino, or acyl;

R 3 is hydrogen or alkyl;

R 4 is aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclylalkyl, or -alkylene-X 1 —R 22 (wherein X 1 is —NR 23 —, —O—, —S(O) n3 —, —CO—, —COO—, —OCO—, —NR 23 CO—, —CONR 23 —, —NR 23 SO 2 —, —SO 2 NR 23 —, —NR 23 COO—, —OCONR 23 —, —NR 23 CONR 24 , or —NR 23 SO 2 NR 24 — where R 23 and R 24 are independently hydrogen, alkyl, or acyl, n3 is 0-2, and R 22 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl) wherein said alkylene chain in R 4 is optionally substituted with one to six halo and wherein the aromatic or alicyclic ring in R 4 is optionally substituted with one, two, or three R d independently selected from alkyl, haloalkyl, alkoxy, hydroxy, haloalkoxy, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl, aralkyl, heteroaralkyl, amino, monsubstituted amino, disubstituted amino, or acyl;

R 5 is hydrogen or alkyl;

R 6 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or -alkylene-X 2 —R 25 (wherein X 2 is —NR 26 —, —O—, —S(O) n4 —, —CO—, —COO—, —OCO—, —NR 26 CO—, —CONR 26 —, —NR 26 SO 2 —, —SO 2 NR 26 —, —NR 26 COO—, —OCONR 26 —, —NR 26 CONR 27 —, or —NR 26 SO 2 NR 27 — where R 26 and R 27 are independently hydrogen, alkyl, or acyl, n4 is 0-2, and R 25 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl) wherein said alkylene chain in R 6 is optionally substituted with one to six halo and the aromatic or alicyclic rings in R 6 are optionally substituted by one, two, or three R e independently selected from alkyl, halo, hydroxy, alkoxy, haloalkyl, haloalkoxy, oxo, cyano, nitro, acyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, cycloalkyl, cycloalkylalkyl, carboxy, or alkoxycarbonyl and further where the aromatic or alicyclic rings in R e is optionally substituted by one, two or three R f independently selected from alkyl, alkoxy, haloalkyl, haloalkoxy, halo, hydroxy, carboxy, cyano, nitro, aryl or cycloalkyl;

R 7 is haloalkyl; and

R 8 is hydrogen, alkyl, alkoxyalkyl or haloalkyl; or

R 6 and R 8 together with the carbon atom to which they are attached form cycloalkylene or heterocyclylalkylene wherein said cycloalkylene is optionally substituted with one or two substituents independently selected from alkyl, haloalkyl, hydroxy, or alkoxy and heterocyclylalkylene is optionally substituted with one or two substituents independently selected from alkyl, haloalkyl, hydroxy, or alkoxy; or

a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein R 1 and R 2 together with the carbon atom to which they are attached form cycloalkylene optionally substituted with one or two R b independently selected from alkyl, halo, dialkylamino, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, alkoxycarbonyl, or aryloxycarbonyl.

3. The compound of claim 1 where R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene, cyclopentylene, or cyclohexylene.

4. The compound of claim 1 wherein R 1 and R 2 together with the carbon atom to which they are attached form pyrrolidinyl, piperidin-4-yl substituted at the 1-position with methyl, ethyl, propyl, n-butyl, or 2,2,2-trifluoroethyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothiopyran-4-yl-1-oxide, or tetrahydrothiopyran-4-yl-1,1-dioxide.

5. The compound of claim 1

wherein:

R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene and R 4 is aralkyl, heteroaralkyl, heterocyclylalkyl, or -alkylene-X 1 —R 22 (wherein X 1 is —NR 23 —, —O—, —S(O) n3 —, —CO—, —COO—, —OCO—, —NR 23 CO—, —CONR 23 —, —NR 23 SO 2 —, —SO 2 NR 23 —, —NR 23 COO—, —OCONR 23 —, —NR 23 CONR 24 , or —NR 23 SO 2 NR 24 — where R 23 and R 24 are independently hydrogen, alkyl, or acyl, n3 is 0-2, and R 22 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl) wherein said alkylene chain in R 4 is optionally substituted with one to six halo and further wherein the aromatic or alicyclic ring in R 4 is optionally substituted with one, two, or three R d independently selected from alkyl, haloalkyl, alkoxy, hydroxy, haloalkoxy, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl, aralkyl, heteroaralkyl, amino, monsubstituted amino, disubstituted amino, or acyl; and

R 3 and R 5 are hydrogen.

6. The compound of claim 2

wherein:

R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene;

R 4 is ethylthiomethyl, ethylsulfinylmethyl, ethylsulfonylmethyl, isopropylthiomethyl, 2-methylthioethyl, 2-methylsulfinylethyl, 2-methysulfonylethyl, 2-methylpropylsulfonylmethyl, isobutylsulfanylmethyl, tert-butylthiomethyl, benzenesulfonylmethyl, 2-phenylsulfanylethyl, 2-phenylsulfonylethyl, naphth-2-ylmethanesulfonylmethyl, biphenyl-2-ylmethanesulfonylmethyl, biphenyl-4-ylmethanesulfonylmethyl, phenylmethanesulfanylmethyl, phenylmethanesulfinylmethyl, phenylmethanesulfonylmethyl, 2-phenylmethanesulfonylethyl, 4-tert-butylphenylmethanesulfonyl-methyl, 2-fluorophenylmethanesulfanylmethyl, 2-fluorophenyl-methanesulfonylmethyl, 3-fluorophenylmethanesulfonylmethyl, 4-fluorophenylmethanesulfonylmethyl, 2-chlorophenyl-methanesulfanylmethyl, 2-chlorophenylmethanesulfonylmethyl, 3-chlorophenylmethanesulfonyl-methyl, 4-chlorophenylmethanesulfonylmethyl, 2-methoxyphenylmethanesulfonylmethyl, 4-methoxyphenylmethanesulfonylmethyl, 2-trifluoromethoxyphenylmethanesulfonylmethyl, 3-trifluoromethoxyphenylmethane-sulfonylmethyl, 4-trifluoromethoxyphenylmethane-sulfonylmethyl, 2-trifluoromethylphenylmethanesulfanylmethyl, 2-trifluoromethylphenylmethane-sulfonylmethyl, 3-trifluoromethylphenylmethane-sulfonylmethyl, 4-trifluoromethylphenylmethane-sulfonylmethyl, 2-cyanophenylmethane-sulfanylmethyl, 2-cyanophenylmethanesulfonylmethyl, 3-cyanophenylmethanesulfonylmethyl, 2-bromophenylmethanesulfonylmethyl, 2-nitrophenyl-methanesulfanylmethyl, 2-nitrophenyl-methanesulfonylmethyl, 2-methylphenylmethane-sulfonylmethyl, 3-methylphenylmethane-sulfonylmethyl, 4-methylphenylmethanesulfonylmethyl, 2-(4-trifluoromethoxy-benzenesulfonyl)ethyl, 2-(3-trifluoromethoxybenzenesulfonyl)-ethyl, 2-(2-trifluoromethoxy-benzenesulfonyl)ethyl, 2-difluoromethoxyphenylmethanesulfonylmethyl, 3-difluoromethoxyphenylmethane-sulfonylmethyl, 4-difluoromethoxyphenylmethane-sulfonylmethyl, 2-(4-difluoromethoxybenzenesulfonyl)ethyl, 2-(2-difluoromethoxybenzene-sulfonyl)ethyl, 2-(3-difluoromethoxybenzenesulfonyl)ethyl, 3-chloro-2-fluorophenylmethane-sulfonylmethyl, 3,5-dimethylphenylmethanesulfonylmethyl, 3,5-bis-trifluoromethylphenyl-methanesulfonylmethyl, 2,5-difluorophenylmethanesulfonylmethyl, 2,6-difluorophenyl-methanesulfonylmethyl, 2,3-difluorophenylmethanesulfonylmethyl, 3,4-difluorophenyl-methanesulfonylmethyl, 2,4-difluorophenylmethanesulfonylmethyl, 2,5-dichloro-phenylmethane-sulfonylmethyl, 3,4-dichlorophenylmethanesulfonylmethyl, 2,6-dichlorophenylmethane-sulfonylmethyl, 2-fluoro-3-methylphenylmethanesulfonylmethyl, 4-fluoro-2-trifluoromethoxy-phenylmethanesulfonylmethyl, 2-fluoro-6-trifluoromethylphenyl-methanesulfonylmethyl, 2-fluoro-3-trifluoromethylphenyl-methanesulfonylmethyl, 2-fluoro-4-trifluoromethylphenyl-methanesulfonylmethyl, 2-fluoro-5-trifluoromethyl-phenylmethanesulfonylmethyl, 4-fluoro-3-trifluoromethyl-phenylmethanesulfonylmethyl, 2-chloro-5-trifluoromethylphenyl-methanesulfonylmethyl, 2,4,6-trifluorophenylmethane-sulfonylmethyl, 2,4,5-trifluorophenylmethanesulfonylmethyl, 2,3,4-trifluorophenylmethane-sulfonylmethyl, 2,3,5-trifluorophenylmethanesulfonylmethyl, 2,5,6-trifluorophenylmethane-sulfonyl-methyl, 3,4,5-trimethoxyphenylmethanesulfonylmethyl, pyridin-2-ylmethanesulfonyl-methyl, pyridin-3-ylmethanesulfonylmethyl, pyridin-4-ylmethanesulfonylmethyl, 2-(pyridin-2-ylsulfonyl)ethyl, 2-(pyridin-4-ylsulfonyl)ethyl, oxypyridin-2-ylmethane-sulfonylmethyl, cyclohexylmethanesulfanylmethyl, cyclohexylmethanesulfinylmethyl, cyclohexylmethane-sulfonylmethyl, 2-cyclohexylethanesulfonylmethyl, cyclohexylmethanesulfonylmethyl, thiophene-2-sulfonylmethyl, 5-chlorothien-2-ylmethane-sulfonylmethyl, or 3,5-dimethyl-isoxazol-4-ylmethanesulfonylmethyl; and R 3 and R 5 are hydrogen.

7. The compound of claim 6

wherein:

R 6 is alkyl, haloalkyl, cycloalkyl, phenyl, benzyl, naphthyl, alkylSO 2 alkyl, cycloalkylSO 2 alkyl, arylSO 2 alkyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, indolinyl, pyranyl, thiopyranyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyridinyl, isoxazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, quinolinyl, benzofuranyl, benzthienyl, benzimidazolyl, benzthiazolyl, benzoisoxazolyl, benzoxazolyl or amino; wherein the aromatic or alicyclic ring in R 6 is optionally substituted by one, two, or three R e ;

each R e is independently alkyl, halo, hydroxy, oxo, carboxy, cyano, nitro, cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, alkoxy, —COR (where R is alkyl), alkoxycarbonyl, aryloxycarbonyl where the aromatic or alicyclic rings in R e may be further optionally substituted by one, two or three R f independently selected from alkyl, alkoxy, haloalkyl, haloalkoxy, halo, hydroxy, carboxy, cyano, nitro, aryl or cycloalkyl.

8. The compound of claim 7 wherein:

R 6 is methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, benzyl, naphthyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, furanyl, thienyl, thiazolyl, imidazolyl, pyridinyl, or pyrazinyl wherein the aromatic or alicylic rings in R 6 are optionally substituted with one, two, or three R e independently selected from methyl ethyl, fluoro, chloro, bromo, iodo, hydroxy, oxo, carboxy, cyano, nitro, cyclopropyl, phenyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, thienyl, imidazolyl, methoxy, acetyl, or methoxycarbonyl wherein the aromatic or alicyclic rings in R e are further optionally substituted with one, two, or three R f independently selected from methyl, cyclopropyl, phenyl, methoxy, fluoro, chloro, hydroxy, or carboxy.

9. The compound of claim 7 wherein:

R 6 is phenyl, 4-methoxyphenyl, 4-chlorophenyl, 2-fluorophenyl 4-fluorophenyl, 2-fluoro-4-chlorophenyl, naphthyl, piperidin-4-yl, furanyl, thienyl, pyridin-4-yl, or pyrazinyl and R 8 is hydrogen or haloalkyl.

10. The compound of claim 9 wherein R 7 is trifluoromethyl and R 8 is hydrogen.

11. The compound of claim 1 wherein:

R 6 and R 8 together with the carbon to which they are attached form cycloalkylene.

12. The compound of claim 1 wherein:

R 6 and R 8 together with the carbon to which they are attached form heterocyclylalkylene.

13. A compound of Formula (I):

wherein:

R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) cycloalkylene optionally substituted with one or two R b independently selected from alkyl, halo, alkylamino, dialkylamino, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, alkoxycarbonyl, or aryloxycarbonyl, (ii) a four atom heterocyclylalkylene ring, or (iii) heterocyclylalkylene optionally substituted with one to four R c independently selected from alkyl, haloalkyl, hydroxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkyloxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, aminoalkyl, acyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, cycloalkylalkyl, —S(O) n2 R 14 , -alkylene-S(O) n2 —R 15 , —COOR 16 ,

-alkylene-COOR 17 , —CONR 18 R 19 , or -alkylene-CONR 20 R 21 (where n2 is 0-2 and R 14 -R 17 , R 18 and R 20 are independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, or heterocyclyl and R 19 and R 21 are independently hydrogen or alkyl) wherein the aromatic or alicyclic ring in the groups attached to cycloalkylene or heterocyclylalkylene is optionally substituted with one, two, or three substituents independently selected from alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryloxycarbonyl, alkoxy, hydroxy, haloalkoxy, halo, carboxy, alkoxycarbonyl, amino, monsubstituted amino, disubstituted amino, or acyl;

R 3 is hydrogen or alkyl;

R 4 is -alkylene-S(O) 2 —R 22 where R 22 is aralkyl, heteroaryalkyl, or cycloalkylalkyl wherein the alkylene chain in R 4 is optionally substituted with one to six halo and further wherein the aromatic or alicyclic ring in R 4 is optionally substituted with one, two, or three R d independently selected from alkyl, haloalkyl, alkoxy, hydroxy, haloalkoxy, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl, aralkyl, heteroaralkyl, amino, monsubstituted amino, disubstituted amino, or acyl;

R 5 is hydrogen or alkyl;

R 6 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or -alkylene-X 2 —R 25 (where X 2 is —NR 26 —, —O—, —S(O) n4 —, —CO—, —COO—, —OCO—, —NR 26 CO—, —CONR 26 —, —NR 26 SO 2 —, —SO 2 NR 26 —, —NR 26 COO—, —OCONR 26 —, —NR 26 CONR 27 —, or —NR 26 SO 2 NR 27 — where R 26 and R 27 are independently hydrogen, alkyl, or acyl, n4 is 0-2, and R 25 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl) wherein said alkylene chain in R 6 is optionally substituted with one to six halo and the aromatic or alicyclic rings in R 6 are optionally substituted by one, two, or three R e independently selected from alkyl, halo, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkoxyalkyl, alkoxyalkyloxy, haloalkyl, haloalkoxy, oxo, cyano, nitro, acyl, aryl, aralkyl, aryloxy, aralkyloxy, arylsulfonyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkyloxy, heteroarylsulfonyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, cycloalkylalkyl, carboxy, alkoxycarbonyl, alkylsulfonyl, aminosulfonyl, or aminoalkyl and further where the aromatic or alicyclic rings in R e is optionally substituted with one, two or three R f independently selected from alkyl, alkoxy, haloalkyl, haloalkoxy, halo, hydroxy, carboxy, cyano, nitro, aryl or cycloalkyl;

R 7 is haloalkyl optionally substituted with alkoxy or alkoxyalkyloxy; and R 8 is hydrogen, alkyl, alkoxyalkyl or haloalkyl; or

R 6 and R 8 together with the carbon atom to which they are attached form cycloalkylene or heterocyclylalkylene wherein said cycloalkylene is optionally substituted with one to four substituents independently selected from alkyl, halo, haloalkyl, hydroxy, or alkoxy and heterocyclylalkylene is optionally substituted with one or two substituents independently selected from alkyl, halo, haloalkyl, cycloalkyl, hydroxy, or alkoxy; or

a pharmaceutically acceptable salts thereof.

14. The compound of claim 13 wherein:

R 1 and R 2 are hydrogen or R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene;

R 3 is hydrogen;

R 4 is —CH 2 —S(O) 2 —R 22 where R 22 is aralkyl, heteroaryalkyl, or cycloalkylalkyl wherein the the aromatic or alicyclic ring in R 4 is optionally substituted with one, two, or three R d independently selected from alkyl, haloalkyl, alkoxy, hydroxy, haloalkoxy, halo, nitro, cyano, carboxy, alkoxycarbonyl, amino, monsubstituted amino, disubstituted amino, or acyl;

R 5 is hydrogen;

R 6 is aryl or heteroaryl wherein the aromatic or alicyclic rings in R 6 are optionally substituted by one, two, or three R e independently selected from alkyl, halo, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkoxyalkyl, alkoxyalkyloxy, haloalkyl, haloalkoxy, oxo, cyano, nitro, acyl, carboxy, alkoxycarbonyl, arylsulfonyl, alkylsulfonyl, aminosulfonyl, or aminoalkyl;

R 7 is haloalkyl; and

R 8 is hydrogen.

15. The compound of claim 14 wherein:

R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene;

R 4 is phenylmethanesulfonylmethyl, 4-tert-butylphenylmethanesulfonylmethyl, 2-fluorophenylmethanesulfonylmethyl, 3-fluorophenylmethanesulfonylmethyl, 4-fluorophenylmethanesulfonylmethyl, 2-chlorophenylmethanesulfonylmethyl, 3-chlorophenylmethanesulfonylmethyl, 4-chlorophenylmethanesulfonylmethyl, 2-methoxyphenylmethanesulfonylmethyl, 4-methoxyphenylmethanesulfonylmethyl, 2-trifluoromethoxyphenylmethanesulfonylmethyl, 3-trifluoromethoxyphenylmethane-sulfonylmethyl, 4-trifluoromethoxyphenylmethane-sulfonylmethyl, 2-trifluoromethylphenylmethanesulfonylmethyl, 3-trifluoromethylphenylmethanesulfonyl-methyl, 4-trifluoromethylphenylmethanesulfonylmethyl, 2-cyanophenylmethanesulfonyl-methyl, 3-cyanophenylmethanesulfonylmethyl, 2-bromophenylmethanesulfonylmethyl, 2-nitrophenylmethanesulfonylmethyl, 2-methylphenylmethanesulfonylmethyl, 3-methylphenylmethanesulfonylmethyl, 4-methylphenylmethanesulfonylmethyl, 2-difluoromethoxyphenylmethanesulfonylmethyl, 3-difluoromethoxyphenylmethane-sulfonylmethyl, 4-difluoromethoxyphenylmethane-sulfonylmethyl, 3-chloro-2-fluorophenyl-methane-sulfonylmethyl, 3,5-dimethylphenylmethanesulfonylmethyl, 3,5-bis-trifluoromethylphenyl-methanesulfonylmethyl, 2,5-difluorophenylmethane-sulfonylmethyl, 2,6-difluorophenylmethanesulfonylmethyl, 2,3-difluorophenylmethane-sulfonylmethyl, 3,4-difluorophenylmethanesulfonylmethyl, 2,4-difluorophenylmethane-sulfonylmethyl, 2,5-dichlorophenylmethanesulfonylmethyl, 3,4-dichlorophenylmethane-sulfonylmethyl, 2,6-dichlorophenylmethanesulfonylmethyl, 2-fluoro-3-methylphenylmethane-sulfonyl-methyl, 4-fluoro-2-trifluoromethoxyphenylmethane-sulfonylmethyl, 2-fluoro-6-trifluoromethylphenylmethanesulfonylmethyl, 2-fluoro-3-trifluoromethylphenyl-methanesulfonylmethyl, 2-fluoro-4-trifluoromethylphenylmethanesulfonylmethyl, 2-fluoro-5-trifluoromethyl-phenylmethanesulfonylmethyl, 4-fluoro-3-trifluoromethyl-phenylmethanesulfonylmethyl, 2-chloro-5-trifluoromethylphenylmethane-sulfonylmethyl, 2,4,6-trifluorophenylmethanesulfonylmethyl, 2,4,5-trifluorophenylmethanesulfonylmethyl, 2,3,4-trifluorophenylmethanesulfonylmethyl, 2,3,5-trifluorophenylmethanesulfonylmethyl, 2,5,6-trifluorophenylmethanesulfonyl-methyl, 3,4,5-trimethoxyphenylmethanesulfonylmethyl, pyridin-2-ylmethanesulfonylmethyl, pyridin-3-ylmethanesulfonylmethyl, pyridin-4-ylmethanesulfonylmethyl, N-oxypyridin-2-ylmethanesulfonylmethyl, 2-trifluoropyridin-6-ylmethanesulfonylmethyl, pyrazin-2-ylmethanesulfonylmethyl, cyclohexylmethanesulfonyl-methyl, cyclopropylmethanesulfonylmethyl, thiophene-2-sulfonylmethyl, 5-chloro-thien-2-ylmethanesulfonylmethyl, or 3,5-dimethylisoxazol-4-ylmethanesulfonylmethyl.

16. The compound of claim 14 wherein:

R 1 and R 2 together with the carbon atom to which they are attached form cyclopropylene;

R 4 phenylmethanesulfonylmethyl, 4-fluorophenylmethanesulfonylmethyl, cyclopropylmethanesulfonylmethyl, pyridin-2-ylmethanesulfonylmethyl, 2-trifluoromethyl-pyridin-6-ylmethanesulfonylmethyl, 2-difluoromethoxyphenylmethanesulfonylmethyl, or pyrazin-2-ylmethanesulfonylmethyl; and

R 6 is furan-2-yl, indol-3-yl, thiophen-2-yl, 1-methylpyrrol-2-yl, 1-phenylsulfonylpyrrol-2-yl, pyridin-2-yl, or phenyl optionally substituted with one, two, or three R e independently selected from alkyl, hydroxyl, or halo.

17. The compound of claim 16 wherein:

R 6 is furan-2-yl, indol-3-yl, thiophen-2-yl, 1-methylpyrrol-2-yl, 1-phenylsulfonyl-pyrrol-2-yl, pyridin-2-yl, phenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 3-chloro-4-hydroxyphenyl, 3-bromophenyl, 4-fluorophenyl, 3,4-difluorophenyl, or 3,4,5-trifluorophenyl; and

R 7 is trifluoromethyl or difluoromethyl.

18. A compound selected from the group consisting of:

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethylamino)-propionamide;

N-(4-cyano-1-ethylpiperidin-4-yl)-3-(phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenyl-ethylamino)propionamide;

N-(4-cyano-1,1-dioxohexahydro-1λ 6 -thiopyran-4-yl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethylamino)-propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(S)-4-hydroxyphenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-furan-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-furan-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-3-bromophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-indol-3-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-indol-3-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-methylethylamino)-propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-1-methylpyrrol-2-yl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(S)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(R)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-phenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(S)-2-hydroxyphenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(R)-4-hydroxyphenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-phenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(S)-4-hydroxyphenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-chlorophenyl)-2(S)-(2,2,2-trifluoro-1(RS)-phenylethylamino)-propionamide;

N-(1-cyanocyclopropyl)-3-(2-chlorophenyl)-2(S)-(2,2,2-trifluoro-1(RS)-4-fluorophenyl-ethylamino)-propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-hydroxyphenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(R)-3-chloro-4-hydroxy-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(S)-3-chloro-4-hydroxy-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-3-chloro-4-hydroxy-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-3-chloro-4-hydroxy-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2-difluoro-1(R)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2-difluoro-1(RS)-thiophen-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-methylcyclopentyl)-2(S)-(2,2,2-trifluoro-1(S)-3-fluoro-4-hydroxy-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-pyridin-2-ylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-4-pyridin-2-ylsulfanyl-2(S)-(2,2,2-trifluoro-1(RS)-4-fluorophenyl-ethylamino)butyramide;

N-(1-cyanocyclopropyl)-4-pyridin-2-ylsulfonyl-2(S)-(2,2,2-trifluoro-1(RS)-4-fluorophenyl-ethylamino)butyramide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-pyridin-2-yl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-phenylmethanesulfonyl-2(R)-(2,2-difluoro-1(R)-thiophen-2-yl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-difluoromethoxyphenylmethanesulfanyl)-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-difluoromethoxyphenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(R)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-thiophen-3-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-yl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-thiophen-2-yl-ethylamino)propionamide;

N-(1-cyanotetrahydropyran-4-yl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-3,4-difluoro-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-1-methylpyrrol-2-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-1-oxo-1-methyl-pyrrol-2-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-3,4,5-trifluoro-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(4-fluorophenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluoro-phenylethylamino)propionamide;

N-(1-cyanotetrahydrothiopyran-4-yl)-3-(4-fluorophenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1cyanocyclopropyl)-3-(4-fluorophenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-3-phenoxy-phenylethylamino)propionamide;

N-(1-cyano-1,1-dioxohexahydro-1λ 6 -thiopyran-4-yl)-3-(4-fluorophenylmethane-sulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-difluoromethoxyphenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(RS)-1-phenylsulfonylpyrrol-2-ylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-difluoromethoxyphenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-trifluoromethylpyridin-6-ylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(RS)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(RS)-1-phenyl-sulfonylpyrrol-2-yl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanotetrahydropyran-4-yl)-3-(2-difluoromethoxyphenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)propionamide;

N-(1-cyano1,1-dioxohexahydro-1λ 6 -thiopyran-4-yl)-3-(2-difluoromethoxyphenyl-methanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-trifluoromethylpyridin-6-ylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(R)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(1-oxopyridin-2-ylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide; and

N-(1-cyanocyclopropyl)-3-(pyridin-2-ylmethanesulfonyl)-2-(2,2,2-trifluoro-1-phenyl-1-trifluoromethylethylamino)-propionamide; or

a pharmaceutically acceptable salt thereof.

19. The compound of claim 18 wherein:

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethyl-amino)propionamide;

N-(1-cyanocyclopropyl)-3-pyridin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-3,4-difluoro-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(4-fluorophenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluoro-phenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-(2-difluoromethoxyphenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)propionamide;

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-4-fluoro-phenylethylamino)propionamide; and

N-(1-cyanocyclopropyl)-3-pyrazin-2-ylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluoro-phenylethylamino)propionamide; and

N-(1-cyanocyclopropyl)-3-(2-trifluoromethylpyridin-6-ylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide; or

a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound of claim 1 in admixture with one or more suitable excipients.

21. A pharmaceutical composition comprising a compound of claim 18 in admixture with one or more suitable excipients.

22. A pharmaceutical composition comprising a compound of claim 19 in admixture with one or more suitable excipients.

23. A compound of claim 19 , wherein the compound is N-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide or a pharmaceutically acceptable salt thereof.