IP Library › Granted Patent US 8,470,819

Granted Patent B2

US 8,470,819 · App. 13/126,086 · Granted Jun 25, 2013

Benzimidazole and aza-benzimidazole carboxamides

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Patent No.: US 8,470,819
App. No.: 13/126,086
Granted: Jun 25, 2013
Kind: B2

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Abstract

This invention provides compounds of Formula I which are PAFR antagonists: I and the pharmaceutically acceptable salts thereof. The compounds are useful for treating PAF-mediated disorders, and can be used in methods for treating atherosclerosis and preventing or reducing risk for atherosclerotic disease events. The compounds are also useful for treating or ameliorating pain, e.g. inflammatory pain and/or nociceptive pain, and for treating or ameliorating autoimmune and/or inflammatory diseases, among other conditions.

Claims (176)

1. A compound having structural Formula I:

and the pharmaceutically acceptable salts thereof wherein:

R 1 is selected from the group consisting of

(a) a 5-membered heterocyclic ring containing 1 to 4 heteroatoms selected from 1 to 4 of N, 0 (zero) to 1 of O, and 0 (zero) to 1 of S, wherein the ring is optionally substituted with R 4 , and

(b) a 6-membered heterocyclic ring containing 1 to 2 of N, wherein the ring is optionally substituted with R 4 ;

R 2 is selected from the group consisting of

(a) —C 1-6 alkyl optionally substituted with one or more substituents selected from the group consisting of:

(i) fluoro,

(ii) hydroxy,

(iii) Hetcy optionally substituted with one or more substituents selected from the group consisting of —F, —OH and methyl, and

(iv) phenyl optionally substituted with one or more substituents selected from the group consisting of —F, —Cl, —OH, —CN, —OC 1-4 alkyl optionally substituted with one or more substituents selected from the group consisting of fluoro and cyano, and —C 1-4 alkyl optionally substituted with one or more substituents selected from the group consisting of fluoro, cyano and —OC(O)C 1-4 alkyl,

(b) —C 3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of:

(i) fluoro,

(ii) hydroxy, and

(iii) —C 1-4 alkyl optionally substituted with one or more of fluoro,

(c) —N(C 1-3 alkyl) 2 optionally substituted with one or more substituents selected from the group consisting of fluoro and hydroxy,

(d) phenyl optionally mono- or di-substituted with R 5 ,

(e) Hetcy optionally substituted with one or more substituents selected from the group consisting of fluoro, hydroxy and methyl

(f) a 5-membered heterocyclic ring containing 1 to 4 heteroatoms selected from 1 to 4 of N, 0 (zero) to 1 of O, and 0 (zero) to 1 of S, wherein the ring is optionally mono- or di-substituted with R 5 , and

(g) a 6-membered heterocyclic ring containing 1 to 2 of N, wherein the ring is optionally mono- or di-substituted with R 5 ;

R 3 is selected from the group consisting of

(a) —C 1-6 alkyl optionally substituted with one or more substituents selected from the group consisting of:

(i) fluoro,

(ii) hydroxy, and

(iii) phenyl optionally substituted with one or more substituents selected from the group consisting of —F, —Cl, —CN, —OH, —OMe, —OC(O)C 1-4 alkyl, —CF 3 and —OCF 3 ,

(b) —C 3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of:

(i) fluoro,

(ii) hydroxy,

(iii) —C 1-4 alkyl optionally substituted with one or more of fluoro, and

(iv) —OC 1-4 alkyl optionally substituted with one or more of fluoro,

(d) a 6-membered heterocyclic ring containing 1 to 2 of N, wherein the ring is optionally mono- or di-substituted with R 5 ;

R 4 is selected independently at each occurrence from the group consisting of (a) —F, (b) —Cl, (c) hydroxy, (d) cyano, (e) oxo, (f) amino, (g) —C 1-6 alkyl optionally substituted with one or more of fluoro, (h) —C 3-6 cycloalkyl optionally substituted with one or more of fluoro, and (i) —OC 1-6 alkyl optionally substituted with one or more of fluoro;

R 5 is selected independently at each occurrence from the group consisting of (a) —F, (b) —Cl, (c) —OH, (d) —OC(O)C 1-4 alkyl, (e) —NR a R b , (f) —CN, (g) —C 1-4 alkyl optionally substituted with one or more of fluoro and (h) —OC 1-4 alkyl optionally substituted with one or more of fluoro;

R a and R b are independently selected from the group consisting of (a) hydrogen, (b) —C 1-4 alkyl optionally substituted with one or more substituents selected from the group consisting of (i) fluoro, (ii) hydroxy and (iii) phenyl optionally substituted with one or more substituents selected from the group consisting of —F, —Cl, —OCH 3 , —CF 3 and —OCF 3 , and (c) —C 3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of fluoro, hydroxy and —C 1-4 alkyl;

or R a and R b together with the nitrogen to which they are both attached represent azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl, each optionally substituted with one or more substituents selected from —OH and —F;

m is the integer 1;

W is selected from N and CH;

y is selected from a bond and —CR 6a R 6b —;

z is selected from the group consisting of hydrogen, fluoro, hydroxy, and —C 1-4 alkyl optionally substituted with one or more of —OH and —F;

R 6a and R 6b are independently selected from the group consisting of (a) —H, (b) hydroxy, (c) —C 1-4 alkyl optionally substituted with one or more of fluoro, (d) —OC 1-4 alkyl optionally substituted with one or more of fluoro and (e) —OC(O)C 1-4 alkyl;

or R 6a and R 6b are joined together with the carbon to which they are both attached to form a —C 3-6 cycloalk-diyl ring; and

Hetcy is selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl.

2. The compound of claim 1 wherein y is a bond.

3. The compound of claim 1 having a structural Formula selected from the group consisting of:

and the pharmaceutically acceptable salts thereof.

4. The compound of claim 3 wherein R 1 is selected from the group consisting of pyridyl, pyrimidinyl, oxadiazolyl, tetrazolyl, triazolyl, pyrazolyl, thiazolyl, and isoxazolyl, each of which is optionally substituted with R 4 .

5. The compound of claim 4 wherein R 1 is selected from the group consisting of pyridyl optionally substituted with R 4 , and oxadiazolyl optionally substituted with R 4 .

6. The compound of claim 4 having a structural Formula selected from the group consisting of:

and pharmaceutically acceptable salts thereof, wherein R 4 is absent or is independently selected at each occurrence from the group consisting of fluoro, chloro, hydroxy, oxo, methyl, —CF 3 , methoxy, ethoxy and cyano.

7. The compound of claim 6 wherein R 3 is selected from the group consisting of —C 1-4 alkyl optionally substituted with phenyl, wherein the phenyl is optionally substituted with 1 to 2 substituents selected from the group consisting of —F, —Cl and —OCF 3 ; —C 3-6 cycloalkyl optionally substituted with methyl; pyridinyl optionally mono- or di-substituted with R 5 ; and phenyl optionally mono- or di-substituted with R 5 .

8. The compound of claim 7 wherein R 2 is selected from the group consisting of optionally substituted —C 1-4 alkyl; optionally substituted —C 3-6 cycloalkyl; optionally substituted Hetcy; and phenyl optionally mono- or di-substituted with R 5 .

9. The compound of claim 8 wherein Hetcy is selected from optionally substituted pyrrolidinyl, optionally substituted piperidinyl and optionally substituted morpholinyl.

10. The compound of claim 9 wherein R 5 is absent or is independently selected at each occurrence from —F, —Cl, -Me, —OMe, —OEt, —CF 3 and —OCF 3 .

11. The compound of claim 10 wherein R 3 is selected from isopropyl; t-butyl; cyclobutyl; cyclopropyl optionally substituted with methyl; and phenyl optionally mono- or di-substituted with R 5 .

12. The compound of claim 11 wherein R 2 is selected from the group consisting of isopropyl; branched butyl; cyclopropyl optionally substituted with methyl; cyclobutyl optionally substituted with methyl; morpholinyl; pyrrolidinyl optionally mono- or di-substituted with fluoro; piperidinyl optionally substituted with hydroxy or fluoro; and phenyl optionally mono- or di-substituted with R 5 .

13. The compound of claim 6 wherein:

a) R 2 is selected from the group consisting of phenyl, 5-membered heterocycle and 6-membered heterocycle, and R 3 is selected from the group consisting of —C 1-6 alkyl and —C 3-6 cycloalkyl, wherein R 2 and R 3 are each optionally substituted; or

b) R 2 is selected from the group consisting of —C 1-6 alkyl, —C 3-6 cycloalkyl, —N(C 1-3 alkyl) 2 and Hetcy, and R 3 is selected from the group consisting of phenyl and 6-membered heterocycle, wherein R 2 and R 3 are each optionally substituted.

14. The compound of claim 6 wherein z selected from the group consisting of —H and hydroxy.

15. The compound of claim 1 selected from the group consisting of:

2-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1,2-diisopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-isopropyl-2-(1-phenylethyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-isopropyl-2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(4-fluorophenyl)-1-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-[3,5-bis(trifluoromethyl)phenyl]-1-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

2-(2,4-difluorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

2-(2,4-dichlorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

2-(3,5-dichlorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-2-[3-(trifluoromethoxy)phenyl]-1H-benzimidazole;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(4-chlorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

2-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

2-pyridin-4-yl-5-[(3-pyrimidin-5-ylpyrrolidin-1-yl)carbonyl]-1-(2,2,2-trifluoroethyl)-1H-benzimidazole;

1-tert-butyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-(4-fluorobenzyl)-2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(2,4-difluorophenyl)-1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(2,4-dichlorophenyl)-1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(3,5-dichlorophenyl)-1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(4-chlorobenzyl)-1-(4-fluorobenzyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-(4-fluorobenzyl)-2-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-(4-fluorobenzyl)-2-pyridin-4-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclopropyl-2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclopropyl-2-(2,4-difluorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclopropyl-2-(2,4-dichlorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-cyclopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-[3,5-bis(trifluoromethyl)phenyl]-1-cyclopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-2-(2,4-difluorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-2-(2,4-dichlorophenyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-cyclobutyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(4-chlorobenzyl)-1-cyclobutyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-2-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-cyclobutyl-2-pyridin-4-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-(1-methylcyclopropyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-phenyl-1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(2,4-difluorophenyl)-1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(2,4-dichlorophenyl)-1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-(3,5-dichlorophenyl)-1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(4-chlorobenzyl)-1-pyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1,2-dipyridin-3-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-pyridin-3-yl-2-pyridin-4-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-methyl-1-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-[3,5-bis(trifluoromethyl)phenyl]-1-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-methyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-2-(trifluoromethyl)-1H-benzimidazole;

2-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-isobutyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-tert-butyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-cyclopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-cyclobutyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(1-methylcyclopropyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(1-methylcyclobutyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-2-(2,2,2-trifluoro-1-methylethyl)-1H-benzimidazole;

2-(1-phenylethyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-phenyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-2-[1-(trifluoromethyl)cyclopropyl]-1H-benzimidazole;

2-(1-fluoro-1-methylethyl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-sec-butyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-(2,4-dichlorophenyl)-2-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

1-(3,5-dichlorophenyl)-2-isopropyl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1H-benzimidazole;

2-isopropyl-5-{[3-(5-methylpyridin-3-yl)pyrrolidin-1-yl]carbonyl}-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-isopropyl-5-{[3-(5-fluoropyridin-3-yl)pyrrolidin-1-yl]carbonyl}-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-isopropyl-5-{[3-(5-methoxypyridin-3-yl)pyrrolidin-1-yl]carbonyl}-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-isopropyl-5-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)pyrrolidin-1-yl]carbonyl}-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-isopropyl-5-{[3-(4H-1,2,4-triazol-4-ylmethyl)pyrrolidin-1-yl]carbonyl}-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-pyridin-3-ylpyrrolidin-3-ol;

1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-(5-methylpyridin-3-yl)pyrrolidin-3-ol;

3-(5-fluoropyridin-3-yl)-1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)pyrrolidin-3-ol;

3-(5-chloropyridin-3-yl)-1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)pyrrolidin-3-ol;

1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-(5-methoxypyridin-3-yl)pyrrolidin-3-ol;

5-[3-hydroxy-1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)pyrrolidin-3-yl]nicotinonitrile;

1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-[5-(trifluoromethyl)pyridin-3-yl]pyrrolidin-3-ol;

1-({2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-(2-methoxypyridin-5-yl)pyrrolidin-3-ol;

5-[(3-fluoro-3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-isopropyl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-isopropyl-5-[(3-pyrimidin-5-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-isopropyl-5-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)pyrrolidin-1-yl]carbonyl}-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-({1-isopropyl-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-pyridin-3-ylpyrrolidin-3-ol;

5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-pyrrolidin-1-yl-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-(3,3-difluoropyrrolidin-1-yl)-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

2-morpholin-4-yl-5-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazole;

1-({1-(1-methylcyclopropyl)-2-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-pyridin-3-ylpyrrolidin-3-ol;

2-({1-(1-methylcyclopropyl)-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-pyridin-3-ylpyrrolidin-3-ol;

1-({2-(3,3-difluoropyrrolidin-1-yl)-1-[4-(trifluoromethoxy)phenyl]-1H-benzimidazol-5-yl}carbonyl)-3-pyridin-3-ylpyrrolidin-3-ol; and

3-isopropyl-6-[(3-pyridin-3-ylpyrrolidin-1-yl)carbonyl]-2-[4-(trifluoro methoxy)phenyl]-3H-imidazo[4,5-b]pyridine;

and the pharmaceutically acceptable salts thereof.

16. The compound of claim 1 selected from the group consisting of: