Cyanoalkylamino derivatives as protease inhibitors

1. A compound of Formula I:

wherein:

X 1 is —S(O) 2 —;

R 1 is hydrogen or (C 1-6 )alkyl;

R 2 is hydrogen or (C 1-6 )alkyl;

R 3 is hydrogen or (C 1-6 )alkyl;

R 6 and R 6a together with the carbon atoms to which they are attached form:

(i) (C 3-7 )monocyclic cycloalkylene;

R 4 and R 5 are each independently hydrogen or (C 1-6 )alkyl; and

Ar is selected from the group consisting of:

(i) —(C 0-3 )alkylene-Ar 1 where Ar 1 is phenyl;

(ii) —(C 0-3 )alkylene-Ar 1 —X 4 —Ar 2 where Ar 1 is as defined above;

(iii) —(C 0-3 )alkylene-Ar 1 —X 4 —Ar 2 —X 5 —Ar 3 where Ar 1 is as defined above; and

(iv) —(C 0-3 )alkylene-Ar 1 —X 4 —Ar 2 —X 5 —Ar 3 —X 6 —Ar 4 where Ar 1 is as defined above;

wherein:

X 4 , X 5 and X 6 are independently selected from the group consisting of a bond,

(C 1-6 )alkylene, —X 7 NR 15 X 8 —, —X 7 NR 15 C(O)X 8 —, —X 7 C(O)NR 15 X 8 —, —X 7 NR 15 C(O)OX 8 —, —X 7 OC(O)NR 15 X 8 —, —X 7 NR 15 C(O)NR 15 X 8 —, —X 7 NR 15 C(NR 15 )NR 15 X 8 —, —X 7 OX 8 —, —X 7 C(O)X 8 , —X 7 C(O)OX 8 —, —X 7 OC(O)X 8 —, —X 7 S(O) 2 NR 15 X 8 —, —X 7 SX 8 —, —X 7 S(O)X 8 —, —X 7 S(O) 2 X 8 —, —X 7 NR 15 S(O) 2 X 8 —, and heteroalkylene, and X 4 and X 7 can additionally be (C 2-6 )alk-1-ynyl, wherein X 7 and X 8 independently are a bond or (C 1-6 )alkylene and each R 15 is hydrogen or (C 1-6 )alkyl; and

Ar 2 , Ar 3 and Ar 4 are independently selected from the group consisting of:

(i) (C 3-8 )cycloalkyl;

(ii) (C 3-8 )cycloalkenyl;

(iii) heterocycloalkyl;

(iv) heterocycloalkenyl;

(v) (C 6-14 )aryl; and

(vi) heteroaryl;

provided that only one of Ar 1 , Ar 2 , Ar 3 , and Ar 4 can be cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl having more than six ring atoms;

and furthermore when Ar 2 , Ar 3 , and Ar 4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl it is optionally substituted with one, two, or three groups independently selected from the group consisting of (C 1-6 )alkyl, (C 1-6 )alkylidene, (C 1-6 )alkylimino, cyano, halo, halo-substituted (C 1-4 )alkyl, imino, nitro, oxo, thioxo, —X 9 NR 16 R 16 , —X 9 NR 16 C(O)R 16 , —X 9 C(O)NR 16 R 16 , —X 9 NR 16 C(O)OR 16 , —X 9 OC(O)NR 16 R 16 , —X 9 NR 16 C(O)NR 16 R 16 , —X 9 NR 16 C(NR 16 )NR 16 R 16 , —X 9 OR 16 , —X 9 C(O)R 16 , —X 9 C(O)OR 16 , —X 9 OC(O)R 16 , —X 9 S(O) 2 NR 16 R 16 , —X 9 P(O)(OR 16 )OR 16 , —X 9 OP(O)(OR 16 )OR 16 , —X 9 SR 16 , —X 9 S(O)R 17 , —X 9 S(O) 2 R 17 , and —X 9 NR 16 S(O) 2 R 17 , wherein X 9 is a bond, (C 1-6 )alkylene, or (C 2-6 )alk-1-ynyl, R 16 at each occurrence independently is hydrogen, (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl, and R 17 is (C 1-6 )alkyl or halo-substituted (C 1-3 )alkyl; and

when Ar 1 , Ar 2 , Ar 3 , and Ar 4 is aryl or heteroaryl it is optionally substituted with one, two, or three groups independently selected from the group consisting of (C 1-6 )alkyl, cyano, halo, halo-substituted (C 1-4 )alkyl, nitro, —X 9 NR 16 R 16 , —X 9 NR 16 C(O)R 16 , —X 9 C(O)NR 16 R 16 , —X 9 NR 16 C(O)OR 16 , —X 9 OC(O)NR 16 R 16 , —X 9 NR 16 C(O)NR 16 R 16 , —X 9 NR 16 C(NR 16 )NR 16 R 16 , —X 9 OR 16 , —X 9 C(O)R 16 , —X 9 C(O)R 16 , —X 9 OC(O)R 16 , —X 9 S(O) 2 NR 16 R 16 , —X 9 P(O)(OR 16 )OR 16 , —X 9 OP(O)(OR 16 )OR 16 , —X 9 SR 16 , —X 9 S(O)R 17 , —X 9 S(O) 2 R 17 , —OS(O) 2 R 17 , —X 9 NR 16 S(O) 2 R 17 , and heteroalkyl wherein X 9 is a bond or (C 1-6 )alkylene, R 16 at each occurrence independently is hydrogen, (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl, and R 17 is (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl; and

individual isomers and mixtures of isomers; and pharmaceutically acceptable salts thereof provided that there are no more than 5 ring systems in a compound of Formula I.

2. The compound of claim 1 wherein R 6 and R 6a together with the carbon atoms to which they are attached form (C 3-7 )monocyclic cycloalkylene, which is optionally substituted with hydroxy or (C 1-3 )alkyl.

3. The compound of claim 1 wherein R 6 and R 6a together with the carbon atoms to which they are attached form:

4. The compound of claim 2 wherein R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen.

5. The compound of claim 4 wherein X 1 is —SO 2 —; and Ar is Ar 1 where Ar 1 is phenyl is optionally substituted with one or two substituents independently selected from (C 1-6 )alkyl, cyano, halo, halo-substituted (C 1-4 )alkyl, nitro, —NR 16 R 16 , —NR 16 C(O)R 16 , —X 9 OR 16 , —X 9 C(O)OR 16 , —SR 16 , —S(O) 2 R 17 and —NR 7 S(O) 2 R 17 .

6. The compound of claim 4 wherein X 1 is —SO 2 —; and Ar is Ar 1 where Ar 1 is phenyl substituted with heteroalkyl.

7. The compound of claim 4 wherein X 1 is —SO 2 —; and Ar is Ar 2 —X 4 —Ar 1 — where Ar 1 is phenyl; and X 4 is a bond, —(C 1-6 )alkylene, —X 7 NR 15 C(O)X 8 —, —X 7 C(O)NR 15 X 8 —, —X 7 OX 8 —, —X 7 SX 8 —, —X 7 S(O)X 8 —, or —X 7 S(O) 2 X 8 .

8. The compound of claim 4 wherein X 1 is —SO 2 —; and Ar is Ar 2 —X 4 —Ar 1 — where Ar 1 is phenyl; and X 4 is heteroalkylene.

9. The compound of claim 4 wherein —Ar 1 —X 4 —Ar 2 is 4-(morpholin-4-yl)phenyl, 4-(1-methylpyrrolidin-2-ylmethoxy)phenyl, 4-(1-methylpiperidin-4-yloxy)phenyl, 4-[2-(morpholin-4-yl-N-oxide)ethoxy]phenyl, 4-(4-thiolphenylsulfanyl)-phenyl, 4-(4-methylpiperazin-1-yl)phenyl, 4-[2-(morpholin-4-yl)ethoxy]phenyl, 4-(4-tert-butoxycarbonylpiperidin-4-yloxy)phenyl, 4-piperidin-4yloxyphenyl, 4-thien-2-ylphenyl, 4-(3-aminophenyl)phenyl, 4-(pyridin-4-ylsulfanyl)phenyl, 4-(2-phenylethylsulfinyl)phenyl, 4-(4-methoxyphenylsulfanyl)phenyl, 4-[2-(phenyl)ethylsulfanyl]-phenyl, 4-(2-aminophenylsulfanyl)-phenyl, 4-(2-chlorophenylmethyl-sulfanyl)phenyl, 4-(2-methylphenylmethylsulfanyl)phenyl, 4-(pyridin-2-ylsulfanyl)phenyl, 4-(4-chlorophenylmethylsulfanyl)phenyl, 4-(3-aminophenyl-sulfanyl)-phenyl, 4-(pyridin-3-ylmethyl-aminocarbonylmethylsulfanyl)phenyl, 4-[2-(2-chloropyridin-3-ylcarbonylamino)-ethylsulfanyl]phenyl, 4-(4-aminophenylsulfanyl)phenyl, 4-[2-(pyridin-4-yl-carbonylamino)-ethylsulfanyl]phenyl, 4-(4-dimethylaminophenylmethylamino-carbonylmethylsulfanyl)phenyl, 4-(thien-2-ylsulfanyl)phenyl, 4-(furan-2-ylmethylsulfanyl)-phenyl, 4-(pyridin-4-ylmethylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(furan-2-yl)ethylaminocarbonylmethylsulfanyl)-phenyl, 4-[2-(pyridin-4-yl)ethylaminocarbonylmethylsulfanyl]phenyl, 4-(1-methylpiperidin-4-ylsulfanyl)phenyl, 4-(2-chlorophenylmethylaminocarbonylmethylsulfanyl)-phenyl, 4-(4-methoxyphenylmethylaminocarbonylmethylsulfanyl)phenyl, 4-(furan-2-ylmethylaminocarbonyl-methylsulfanyl)phenyl, 4-(4-chlorophenylmethylaminocarbonyl-methylsulfanyl)phenyl, 3-fluoro-4-(1-methylimidazol-2-ylsulfanyl)phenyl, 4-(3-dimethylaminophenylmethylaminocarbonyl-methylsulfanyl)phenyl, 3-fluoro-4-[2-(phenyl)ethylsulfanyl]phenyl, 3-fluoro-4-(pyrimidin-2-ylsulfanyl)phenyl, 4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(1-tert-butylpiperazin-1-ylcarbonylmethylsulfanyl)phenyl, 4-[2-(phenyl)ethylsulfonyl]phenyl, 3-fluoro-4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(4-tert-butylpiperazin-1-ylcarbonylmethoxy)phenyl, 4-(2-phenylethoxy)phenyl, 4-[2-(thien-2-yl)ethylaminocarbonylmethylsulfonyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfonyl]phenyl, 3-fluoro-4-[2-(phenyl)ethylsulfonyl]phenyl, 4-[2-(pyridin-4-yl)ethylaminocarbonylmethyl-oxy]phenyl, 4-(3-methyl-[1,3,5]oxadiazol-4-ylmethylamino-carbonylmethylsulfanyl)phenyl, 4-[(2-morpholin-4-ylcarbonylamino)-ethylsulfanyl]phenyl, 4-[2-(pyridin-3-yloxy)ethylsulfanyl]-phenyl, 4-(piperidin-3-ylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(morpholin-4-ylcarbonylamino)-ethyloxy]phenyl, 4-[2-(morpholin-4-yl)ethylaminocarbonyl-methylsulfanyl]-phenyl, 4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(4-isopropylpiperazin-4-ylcarbonylmethylsulfanyl)phenyl, 4-(furan-2-ylmethylaminocarbonylmethyl)phenyl, 4-[2-(furan-2-ylmethylaminocarbonyl)-ethyl]phenyl, 4-benzylsulfanylmethylphenyl, 4-(benzylsulfonyl-methyl)phenyl, 4-[3-(furan-2-ylmethylaminocarbonyl)propyl]phenyl, 4-[2-(pyridin-2-yl)-ethylsulfanylmethyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfonylmethyl]phenyl, 4-(thien-2-ylethylaminocarbonylmethylsulfonyl)-phenyl, or 4-(furan-2-ylmethylaminocarbonyl)phenyl.

10. The compound of claim 1 wherein R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen;

R 6 and R 6a together with the carbon atoms to which they are attached form (C 3-7 )monocyclic cycloalkylene; where monocycloalkylene is optionally substituted with alkyl;

X 1 is —S—, or SO 2 —; and

Ar is:

(i) phenyl optionally substituted with one or two substituents independently selected from (C 1-6 )alkyl, cyano, halo, halo-substituted (C 1-4 )alkyl, nitro, —X 9 NR 16 R 16 , —C(O)R 16 , —NR 16 C(O)R 16 , —X 9 OR 16 , —X 9 C(O)OR 16 , —SR 16 , —S(O) 2 R 17 , —OS(O) 2 R 17 and —NR 7 S(O) 2 R 17 where X 9 is a bond or (C 1-6 )alkylene, R 16 at each occurrence independently is hydrogen, (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl, and R 17 is (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl; or

(ii) phenyl optionally substituted with heteroalkyl; or

(iii) —Ar 1 —X 4 —Ar 2 where Ar 1 is phenyl, X 4 is selected from the group consisting of a bond, —X 7 NR 15 C(O)X 8 —, —X 7 OX 8 —, —X 7 SX 8 —, —X 7 S(O)X 8 —, and —X 7 S(O) 2 X 8 — wherein X 7 and X 8 independently are a bond or —(C 1-6 )alkylene and R 15 is hydrogen or —(C 1-6 )alkyl; or X 4 is heteroalkylene; and Ar 2 is phenyl optionally substituted with (C 1-6 )alkyl, —OR 16 , halo, or —NR 16 R 16 ; or heteroaryl containing five or six ring atoms wherein one, two or three rings atoms are heteroatoms selected from the group consisting of nitrogen, oxygen or sulfur and wherein the heteroaryl ring is optionally substituted with a group selected from halo; or heterocycloalkyl ring of six ring atoms wherein one or two ring atoms are independently selected from nitrogen or oxygen and wherein said heterocycloalkyl ring is optionally substituted with a substituent selected from (C 1-6 )alkyl, or —OC(O)R 16 where R 16 at each occurrence independently is hydrogen, (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl; or

(iv) Ar 3 —X 5 —Ar 2 —X 4 —Ar 1 — where Ar 1 is phenyl; X 4 is bond or —COCH 2 S—; Ar 2 is 5 or 6 membered heteroaryl ring containing one or two heteroatoms selected from nitrogen or sulfur or 6 membered heterocycloalkyl ring containing one or two nitrogen atoms; X 5 is bond, —O—, or alkylene; and Ar 3 is phenyl optionally substituted with halo; a 6 membered heterocycloalkyl ring containing one or two nitrogen atoms and optionally substituted with (C 1-6 )alkyl, or —OC(O)R 16 where R 16 at each occurrence independently is hydrogen, (C 1-6 )alkyl, or halo-substituted (C 1-3 )alkyl; or a 5 or 6 membered heteroaryl ring containing one or two heteroatoms selected from nitrogen or sulfur.

11. The compound of claim 10 wherein R 6 and R 6a form:

12. The compound of claim 11 wherein Ar is 4-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-(-NHCOCH 3 )phenyl., 4-nitrophenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-methylsulfanylphenyl, 4-methylsulfonylphenyl, 4-hydroxyphenyl, 4-aminophenyl, 2-chlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2-methylphenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-chlorophenyl, 4-dimethylaminophenyl, 3-methylphenyl, 4-trifluoromethoxyphenyl, 3-methoxyphenyl, 3,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 4-thiolphenyl, 4-isopropyloxyphenyl, 3-trifluoromethylphenyl, 3-(-NHCOCH 3 )phenyl, 3-fluorophenyl, 3-aminophenyl, 3-carboxymethylphenyl, 4-carboxyphenyl, 3-hydroxyphenyl, 3-formylaminophenyl, 3-trifluoroacetylaminophenyl, 4-hydroxymethylphenyl, 4-trifluorosulfonyloxyphenyl, 3-carboxylphenyl, 4-ethylsulfanylphenyl, 3-methylsulfonylaminophenyl, 3,4-dimethylsulfanylphenyl, 3,4-difluorophenyl, 4-tert-butylsulfanylphenyl, 2,4-difluorophenyl, 3-fluoro-4-methylsulfanylphenyl, 4-(3-carboxypropyl)phenyl, 4-(2-carboxyethyl)phenyl, 4-carboxymethyl-phenyl, 4-iodophenyl, 4-(2,2,2-trifluoroethylsulfanyl)phenyl, 4-difluoromethoxyphenyl, 4-difluoromethylsulfanylphenyl, 4-ethoxycarbonylmethylsulfanylphenyl, 3-hydroxypropylsulfanylphenyl, 2-aminoethylsulfanylphenyl, 4-(2-tert-butoxycarbonylaminoethylsulfanyl)phenyl, 4-[2-(2,2,2-trifluoroethylamino)-ethylsulfanyl]phenyl, 4-methylaminocarbonylmethylsulfanylphenyl, 4-[2-(acetylamino)ethoxy]-phenyl, 4-[2-aminoethylsulfanyl]phenyl, 4-[2-(acetylamino)ethylsulfanyl]phenyl, 3-fluoro-4-[2-(ethylsulfonylamino)ethylsulfanyl]phenyl, 3-fluoro-4-[2-(dimethylaminosulfonylamino)-ethylsulfanyl]phenyl, 4-[2-(methylsulfonyloxy)ethylsulfanyl]phenyl, 4-[2-hydroxyethyl-sulfanyl]phenyl, 4-methoxycarbonylmethoxyphenyl, 4-[1-ethoxycarbonylethylsulfanyl]phenyl, 4-trifluoromethylsulfonyloxyphenyl, or 4-[2-bromoethylsulfanyl]phenyl, 4-(morpholin-4-yl)phenyl, 4-(1-methylpyrrolidin-2-ylmethoxy)phenyl, 4-(1-methylpiperidin-4-yloxy)phenyl, 4-[2-(morpholin-4-yl-N-oxide)ethoxy]phenyl, 4-(4-thiolphenylsulfanyl)-phenyl, 4-(4-methylpiperazin-1-yl)phenyl, 4-[2-(morpholin-4-yl)ethoxy]phenyl, 4-(4-tert-butoxycarbonylpiperidin-4-yloxy)phenyl, 4-piperidin-4-yloxyphenyl, 4-thien-2-ylphenyl, 4-(3-aminophenyl)phenyl, 4-(pyridin-4-ylsulfanyl)phenyl, 4-(2-phenylethylsulfinyl)phenyl, 4-(4-methoxyphenylsulfanyl)phenyl, 4-[2-(phenyl)ethylsulfanyl]-phenyl, 4-(2-aminophenylsulfanyl)-phenyl, 4-(2-chlorophenyl-methylsulfanyl)phenyl, 4-(2-methylphenylmethylsulfanyl)phenyl, 4-(pyridin-2-ylsulfanyl)phenyl, 4-(4-chlorophenylmethylsulfanyl)phenyl, 4-(3-aminophenyl-sulfanyl)-phenyl, 4-(pyridin-3-ylmethylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(2-chloropyridin-3-ylcarbonylamino)ethyl-sulfanyl]phenyl, 4-(4-aminophenylsulfanyl)phenyl, 4-[2-(pyridin-4-ylcarbonylamino)-ethylsulfanyl]phenyl, 4-(4-dimethylaminophenylmethylaminocarbonylmethylsulfanyl)phenyl, 4-(thien-2-ylsulfanyl)phenyl, 4-(furan-2-ylmethylsulfanyl)-phenyl, 4-(pyridin-4-ylmethylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(furan-2-yl)ethylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(pyridin-4-yl)ethylaminocarbonylmethylsulfanyl]phenyl, 4-(1-methylpiperidin-4-ylsulfanyl)phenyl, 4-(2-chlorophenylmethylaminocarbonylmethylsulfanyl)-phenyl, 4-(4-methoxyphenylmethylaminocarbonylmethylsulfanyl)phenyl, 4-(furan-2-ylmethylamino-carbonylmethylsulfanyl)phenyl, 4-(4-chlorophenylmethylaminocarbonyl-methylsulfanyl)phenyl, 3-fluoro-4-(1-methylimidazol-2-ylsulfanyl)phenyl, 4-(3-dimethylaminophenylmethylaminocarbonylmethylsulfanyl)phenyl, 3-fluoro-4-[2-(phenyl)ethylsulfanyl]phenyl, 3-fluoro-4-(pyrimidin-2-ylsulfanyl)phenyl, 4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(1-tert-butylpiperazin-1-ylcarbonylmethylsulfanyl)phenyl, 4-[2-(phenyl)ethylsulfonyl]phenyl, 3-fluoro-4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(4-tert-butylpiperazin-1-ylcarbonylmethoxy)phenyl, 4-(2-phenylethoxy)phenyl, 4-[2-(thien-2-yl)ethylaminocarbonylmethylsulfonyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfonyl]phenyl, 3-fluoro-4-[2-(phenyl)ethylsulfonyl]phenyl, 4-[2-(pyridin-4-yl)ethylaminocarbonylmethyl-oxy]phenyl, 4-(3-methyl-[1,3,5]oxadiazol-4-ylmethylamino-carbonylmethylsulfanyl)phenyl, 4-[(2-morpholin-4-ylcarbonylamino)-ethylsulfanyl]phenyl, 4-[2-(pyridin-3-yloxy)ethylsulfanyl]-phenyl, 4-(piperidin-3-ylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(morpholin-4-ylcarbonylamino)-ethyloxy]phenyl, 4-[2-(morpholin-4-yl)ethylaminocarbonyl-methylsulfanyl]-phenyl, 4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(4-isopropylpiperazin-4-ylcarbonylmethylsulfanyl)phenyl, 4-(furan-2-ylmethylaminocarbonylmethyl)phenyl, 4-[2-(furan-2-ylmethylaminocarbonyl)-ethyl]phenyl, 4-benzylsulfanylmethylphenyl, 4-(benzylsulfonyl-methyl)phenyl, 4-[3-(furan-2-ylmethylaminocarbonyl)propyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfanylmethyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfonylmethyl]phenyl, 4-(thien-2-ylethylaminocarbonylmethylsulfonyl)-phenyl, or 4-(furan-2-ylmethylaminocarbonyl)phenyl, 4-[2-(4-isopropylpiperazin-1-yl)thiazol-4-yl]phenyl, 4-[4-(tert-butoxycarbonylpiperazin-1-yl)-phenyl]phenyl, 4-[4-(piperazin-1-yl)phenyl]phenyl, 4-[4-(morpholin-4-yl)piperidin-1-yl]phenyl, 4-[4-(piperidin-1-yloxy)phenyl]phenyl, 4-[4-(pyridin-4-yl)piperazin-1-ylcarbonylmethylsulfanyl]phenyl, 4-[4-(pyridin-2-yl)piperazin-1-ylcarbonylmethylsulfanyl]phenyl, 4-[4-(pyrimidin-2-yl)piperazin-1-ylcarbonylmethylsulfanyl]phenyl, 4-[4-(4-bromophenyl)piperazin-1-ylcarbonylmethylsulfanyl]-phenyl, or 4-[4-benzylpiperidin-4-ylaminocarbonyl-methylsulfanyl]phenyl.

13. The compound of claim 11 wherein Ar is 4-[2-(pyridin-4-yl)ethylamino-carbonylmethylsulfanyl]phenyl, 4-[2-(morpholin-4-yl)ethylaminocarbonyl-methylsulfanyl]phenyl, 4-[2-(pyridin-2-yl)ethylsulfanyl]phenyl, 4-(2-phenylethylsulfanyl)phenyl, 4-(4-dimethylaminophenylmethylaminocarbonylmethyl-sulfanyl)phenyl, 4-[2-(pyridin-3-yloxy)ethylsulfanyl]phenyl, 4-(4-chlorophenylmethylaminocarbonylmethylsulfanyl)phenyl, 3-fluoro-4-(pyridin-2-ylethylsulfanyl)phenyl, 4-(piperidin-3-ylaminocarbonylmethylsulfanyl)-phenyl, 4-(2-chlorophenylmethylamino-carbonylmethylsulfanyl)phenyl, 4-(pyridin-3-ylmethylamino-carbonylmethylsulfanyl)phenyl, 4-[2-(thien-2-yl)ethylaminocarbonylmethyl-sulfanyl]phenyl, 4-(3-dimethylaminophenylmethylaminocarbonylmethylsulfanyl)phenyl, 4-[2-(pyridin-4-ylcarbonylamino)ethylsulfanyl]phenyl, 4-(4-methoxyphenylmethylaminocarbonylmethylsulfanyl)phenyl, 4-(4-isopropylpiperazin-1-ylcarbonylmethylsulfanyl)phenyl, or 4-(furan-2-ylmethylsulfanyl)phenyl, 4-hydroxyphenyl, 4-methylsulfanylphenyl, 4-[2-aminoethyl-sulfanyl]phenyl, 4-[2-(methylsulfonyloxy)ethylsulfanyl]-phenyl, 4-[2-tert-butoxycarbonyl-aminoethylsulfanyl]phenyl, or 4-[2-bromoethylsulfanyl]phenyl, 4-[4-(piperazin-1-yl)phenyl]-phenyl, 4-[4-(pyridin-4-yl)piperazin-1-ylcarbonylmethylsulfanyl]-phenyl, 4-[4-(piperidin-1-yloxy)phenyl]phenyl, or 4-[4-benzylpiperidin-4-ylaminocarbonyl-methylsulfanyl]phenyl.

14. A compound selected from the group consisting of:

trans-N-cyanomethyl-2-(4-fluorophenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-piperazin-1-ylphenyl)phenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-bromophenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-bromophenylsulfinylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-bromobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(phenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-chlorophenylsulfanylmethyl)cyclohexanecarboxamide;

trans N-cyanomethyl-2-(3,4-dichlorophenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylphenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methoxyphenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(morpholin-4-yl)phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(morpholin-4-yl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylcarbonylaminophenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(benzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-chlorobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(3,4-dichlorobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylbenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methoxybenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-nitrophenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-tert-butylphenylsulfanylmethyl)cyclohexanecarboxamide.

trans-N-cyanomethyl-2-(4-trifluoromethylphenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylsulfanylphenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-fluorobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylcarbonylaminobenzenesulfonylmethyl)-cyclohexane-carboxamide;

trans-N-cyanomethyl-2-(4-nitrobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-tert-butylbenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methylsulfonylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-hydroxyphenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-aminobenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-trifluoromethylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-hydroxybenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-{4-[2-(4-isopropylpiperazin-1-yl)thiazol-4-yl]benzenesulfonylmethyl}cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-thiolphenylsulfanyl)phenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-{4-[4-(4-tert-butoxycarbonylpiperazin-1-yl)phenyl]-phenylsulfanylmethyl}cyclohexanecarboxamide

trans-N-cyanomethyl-2-(2,4-dichlorobenzylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(2,4-dichlorophenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-methylpyrrolidin-2-ylmethyloxy)phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-dimethylaminophenylsulfanylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-dimethylaminobenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-trifluoromethoxyphenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(3,4-dimethoxyphenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-methylpiperidin-4-yloxy)phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(3-dimethylaminopropyloxy)phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-morpholin-4-ylethyloxy)benzenesulfonylmethyl]-cyclohexanecarboxamide N-oxide;

trans-N-cyanomethyl-2-[4-(1-methylpiperazinyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-morpholin-4-ylpiperidin-1-yl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methoxyphenylsulfanylmethyl)-cyclopentanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-tert-butoxypiperidin-4-yloxy)phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-tert-butoxypiperidin-4-yloxy)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-6-(4-fluorobenzenesulfonylmethyl)cyclohex-3-enecarboxamide;

trans-N-cyanomethyl-6-(4-methylsulfanylbenzenesulfonylmethyl)cyclohex-3-enecarboxamide;

trans-N-cyanomethyl-2-(3-carboxymethylphenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-thien-3-ylbenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(3-trifluoroacetylaminophenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(3-methylsulfonylaminophenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-ethoxycarbonylmethylsulfanylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-pyridin-4-yloxyphenyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(3-aminophenyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(pyridin-4-ylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-phenylethylsulfinyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-phenylethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-aminoethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-chlorophenylmethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-tert-butoxycarbonylaminoethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-(2,2,2-trifluoroethylamino)ethylsulfanyl)benzenesulfonyl-methyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(pyridin-3-ylmethylaminocarbonylmethylsulfanyl)benzene-sulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-(2-chloropyridin-3-ylcarbonylamino)ethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-pyridin-4-ylcarbonylaminoethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-acetylaminoethyloxy)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-dimethylaminophenylmethylaminocarbonylmethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[3-fluoro-4-(2-aminoethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(pyridin-4-ylmethylaminocarbonylmethylsulfanyl)benzene-sulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-thien-2-ylethylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-pyridin-4-ylethylaminocarbonylmethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[3-fluoro-4-(2-ethylsulfonylaminoethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-chlorophenylmethylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-methoxybenzylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(furan-2-ylmethylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-chlorophenylmethylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[3-fluoro-4-(2-dimethylsulfonylaminoethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-methylsulfonyloxyethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(3-dimethylaminobenzylaminocarbonylmethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-pyridin-4-ylpiperazin-1-ylcarbonylmethylsulfanyl)-benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-methoxycarbonylmethyloxybenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-ethyloxycarbonylethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-tert-butylpiperazin-4-ylcarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-pyridin-2-ylpiperazin-4-ylcarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-tert-butylpiperazin-4-ylcarbonylmethyloxy)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-pyrimidin-2-ylpiperazin-4-ylcarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-thien-2-ylethylaminocarbonylmethylsulfonyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-{4-[1-(4-bromophenyl)piperazin-4-ylcarbonylmethylsulfanyl]-benzenesulfonylmethyl}-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-pyridin-4-ylethylaminocarbonylmethyloxy)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(3-methyl-1,2,5-oxadiazol-4-ylmethylaminocarbonylmethyl-sulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-morpholin-4-ylcarbonylaminoethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(pyridin-3-yloxyethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-morpholin-4-ylcarbonylaminoethyloxy)-benzenesulfonyl-methyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(1-benzylpiperidin-4-ylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(furan-2-ylmethylaminocarbonylmethyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-furan-2-ylmethylaminocarbonylethyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-furan-2-ylmethylaminocarbonylethyl)-phenylsulfanylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(benzylsulfanylmethyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-bromoethylsulfanyl)-benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-2-(4-fluorophenylsulfanylmethyl)-4-methylcyclopentanecarboxylic acid cyanomethylamide;

trans-N-cyanomethyl-2-(4-fluorophenylsulfanylmethyl)-5-methylcyclohexanecarboxamide;

cis-N-cyanomethyl-2-(4-methylsulfanylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[1-(4-methylsulfanylbenzenesulfonyl)ethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-{4-[3-(2-morpholin-4-ylethylaminocarbonyl)propyl]-phenylsulfanylmethyl}cyclohexanecarboxamide;

(R,R)-N-cyanomethyl-2-(4-methylsulfanylbenzenesulfonylmethyl)cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-morpholin-4-ylethylaminocarbonylmethylsulfanyl)-benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-pyridin-2-ylethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

(1R/S,2R/S,5R/S)trans-N-cyanomethyl-2-(4-methylsulfanylbenzenesulfonylmethyl)-5-methylcyclohexane-carboxamide;

trans-N-cyanomethyl-2-(4-methylsulfanylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[3-fluoro-4-(2-pyridin-2-ylethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(piperidin-3-ylaminocarbonylmethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxamide;

trans-2-[4-(pyridin-2-ylethylsulfanyl)benzenesulfonylmethyl]cyclohexanecarboxylic acid (1-cyanocyclopropyl)amide;

trans-N-cyanomethyl-2-[4-(4-isopropylpiperazin-1-ylcarbonylmethylsulfanyl)benzene-sulfonylmethyl]cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(furan-2-ylmethylsulfanyl)benzenesulfonylmethyl]-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(3-hydroxypropylsulfanylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(4-thiolphenylsulfanyl)phenylsulfanylmethyl)-cyclohexanecarboxamide;

trans-2-{[(4-chlorophenyl)sulfanyl]methyl}-N-(cyanomethyl)cyclopentanecarboxamide;

trans-N-(cyanomethyl)-2-{[(4-fluorophenyl)sulfanyl]methyl}cyclopentanecarboxamide;

trans-2-{[(3-bromophenyl)sulfanyl]methyl}-N-(cyanomethyl)cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-{[(3-fluorophenyl)sulfanyl]methyl}cyclohexanecarboxamide;

trans-2-{[(3-aminophenyl)sulfanyl]methyl}-N-(cyanomethyl)cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-({[3-(trifluoromethyl)phenyl]sulfanyl}methyl)-cyclohexanecarboxamide;

3-{[(trans-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)methyl]sulfanyl}benzoic acid;

4-{[(trans-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)methyl]sulfanyl}benzoic acid;

trans-N-(cyanomethyl)-2-{[(3-hydroxyphenyl)sulfanyl]methyl}cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-({[3-(formylamino)phenyl]sulfanyl}methyl)-cyclohexanecarboxamide;

trans-2-({[3-(acetylamino)phenyl]sulfanyl}methyl)-N-(cyanomethyl)cyclohexanecarboxamide;

trans-2-[({3-[bis(methylsulfonyl)amino]phenyl}sulfanyl)methyl]-N-(cyanomethyl)-cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-{[(4-iodophenyl)sulfanyl]methyl}cyclopentanecarboxamide;

trans-N-(cyanomethyl)-2-{[4-iodobenzenesulfonyl]methyl}cyclopentanecarboxamide;

trans-N-(cyanomethyl)-2-{4-fluorobenzenesulfonylmethyl}cyclopentanecarboxamide;

trans-N-(cyanomethyl)-2-({4-methylsulfanylbenzenesulfonyl}methyl)-cyclopentanecarboxamide;

trans-N-(cyanomethyl)-2-{[(4-iodophenyl)sulfanyl]methyl}cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-{4-iodobenzenesulfonylmethyl}cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-[({4-[(2,2,2-trifluoroethyl)sulfanyl]benzene}sulfonyl)methyl]-cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-[({4-[(difluoromethyl)sulfanyl]phenyl}sulfanyl)methyl]-cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-[({4-[(difluoromethyl)sulfanyl]benzene}sulfonyl)methyl]-cyclohexanecarboxamide;

N-(cyanomethyl)-2-{4-fluorobenzenesulfonylmethyl}-4-methylcyclopentane-carboxamide;

N-(cyanomethyl)-4-methyl-2-({4-methylsulfanylbenzenesulfonyl}methyl)-cyclopentane-carboxamide;

N-(cyanomethyl)-2-{4-fluorobenzenesulfonylmethyl}-5-methylcyclohexane-carboxamide;

trans-N-(cyanomethyl)-2-({4-difluoromethoxybenzenesulfonyl}methyl)cyclohexane-carboxamide;

trans-N-(cyanomethyl)-2-{[4-(methylsulfanyl)phenoxy]methyl}cyclohexanecarboxamide;

trans-N-(cyanomethyl)-2-(1-{4-methylsulfanylbenzenesulfonyl}ethyl)cyclohexanecarboxamide;

trans-2-(4-methoxybenzylsulfonylmethyl)-cyclohexanecarboxylic acid cyanomethyl-amide;

trans-N-cyanomethyl-2-(4-carboxymethylsulfanylbenzenesulfonylmethyl)cyclohexane-carboxamide;

trans-N-(cyanomethyl)-2-({[4-(methylsulfanyl)phenyl]sulfanyl}-methyl)cyclopentane-carboxamide;

(1R,2R)-N-(cyanomethyl)-2-({[4-(methylsulfanyl)benzene]sulfonyl}methyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-(4-hydroxymethylbenzenesulfonylmethyl)-cyclohexanecarboxamide; and

trans-N-cyanomethyl-2-(4-benzylsulfonylmethylbenzenesulfonylmethyl)-cyclohexanecarboxamide;

trans-N-cyanomethyl-2-[4-(2-morpholin-4-ylethyloxy)phenylsulfanylmethyl]-cyclohexanecarboxamide;

a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable excipient.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 14 in combination with a pharmaceutically acceptable excipient.

17. A method of treating osteoporosis, which method comprises administering to a human a pharmaceutical composition comprising a therapeutically effective amount of compound of claim 1 in combination with a pharmaceutically acceptable excipient.