IP Library › Granted Patent US 8,592,426

Granted Patent B2

US 8,592,426 · App. 13/351,253 · Granted Nov 26, 2013

Aryl-benzocycloalkyl amide derivatives

Inventors: Johannes Aebi (Binningen, CH); Alfred Binggeli (Binningen, CH); Cornelia Hertel (Brislach, CH); Anish Ashok Konkar (Binningen, CH); Holger Kuehne (Loerrach, DE); Bernd Kuhn (Reinach BL, CH); Hans P. Maerki (Basel, CH); Haiyan Wang (Allschwil, CH)

Assignee: Hoffmann—La Roche Inc.

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Quick Facts

Patent No.: US 8,592,426
App. No.: 13/351,253
Granted: Nov 26, 2013
Kind: B2

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Abstract

The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , A 1 , A 2 and n are as described herein, compositions including the compounds and methods of using the compounds.

Claims (133)

1. A compound according to formula (I)

wherein

R 1 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkoxy, halocycloalkoxyalkyl, alkoxycarbonyl, cycloalkoxycarbonyl, haloalkoxycarbonyl, halocycloalkoxycarbonyl, cyano, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein substituted aryl and substituted heteroaryl are substituted with one to three substituents independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylalkoxyalkyl, cycloalkoxy, cycloalkoxyalkyl, alkylcycloalkylalkyl, halocycloalkyl, halocycloalkylalkyl, halogen, cyano, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, amino and substituted amino, wherein substituted amino is substituted with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;

R 2 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

R 3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

R 4 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

R 5 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

R 6 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

R 7 is selected from the group consisting of hydrogen, alkyl and cycloalkyl;

R 8 is selected from the group consisting of hydrogen, alkyl and cycloalkyl;

R 9 and R 10 together with the carbon they are attached to form a cycloalkyl or a oxetanyl;

R 11 is selected from the group consisting of hydrogen, alkyl and cycloalkyl;

R 12 is selected from the group consisting of hydrogen, alkyl, cycloalkyl and —C(O)—R 13 ;

R 13 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkoxy, cycloalkoxy, halocycloalkoxy, alkoxyalkyl, cycloalkoxyalkyl, haloalkyl, haloalkoxyalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkoxyalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein substituted aryl and substituted heteroaryl are substituted with one to three substituents independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylalkoxyalkyl, cycloalkoxy, cycloalkoxyalkyl, alkylcycloalkylalkyl, halocycloalkyl, halocycloalkylalkyl, halogen, cyano, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, hydroxyalkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, hydroxyhaloalkyl, amino and substituted amino, wherein substituted amino is substituted with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;

R 14 is selected from the group consisting of hydrogen, alkyl, alkoxy and cycloalkyl;

R 15 is selected from the group consisting of hydrogen, alkyl and cycloalkyl;

R 16 is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, cycloalkyl, cyano and halogen;

A 1 is selected from the group consisting of CR 14 , O, and S;

A 2 is CR 16 or N; and

n is 1;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein R 1 is selected from the group consisting of haloalkoxy, alkoxycarbonyl, cycloalkoxycarbonyl, haloalkoxycarbonyl, heteroaryl and substituted heteroaryl, wherein substituted heteroaryl is substituted with one to three alkyl.

3. A compound according to claim 1 , wherein R 2 is hydrogen or halogen.

4. A compound according to claim 1 , wherein R 3 is hydrogen.

5. A compound according to claim 1 , wherein R 4 is hydrogen or halogen.

6. A compound according to claim 1 , wherein R 5 is hydrogen.

7. A compound according to claim 1 , wherein R 6 is hydrogen.

8. A compound according to claim 1 , wherein R 7 is hydrogen or alkyl.

9. A compound according to claim 1 , wherein R 8 is hydrogen.

10. A compound according to claim 1 , wherein R 11 is hydrogen.

11. A compound according to claim 1 , wherein R 12 is selected from the group consisting of hydrogen, alkyl and cycloalkyl.

12. A compound according to claim 1 , wherein R 12 is —C(O)—R 13 .

13. A compound according to claim 1 , wherein R 13 is selected from the group consisting of

alkoxy, alkoxyalkyl, cycloalkoxyalkyl, haloalkyl, haloalkoxyalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkoxyalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein substituted aryl and substituted heteroaryl are substituted with one to three substituents independently selected from the group consisting of alkyl, cycloalkyl, halogen, cyano, haloalkyl, alkoxy, alkoxyalkyl, amino and substituted amino, wherein substituted amino is substituted with one to two substituents independently selected from alkyl and cycloalkyl.

14. A compound according to claim 1 , wherein A 2 is CR 16 .

15. A compound according to claim 1 , wherein A 2 is N.

16. A compound according to claim 1 , wherein R 14 is hydrogen.

17. A compound according to claim 1 , wherein R 15 is hydrogen.

18. A compound according to claim 1 , wherein R 16 is hydrogen or halogen.

19. A compound according to claim 1 , selected from the group consisting of

(rac)-2-(1-{[1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarbonyl]-amino}-indan-5-yl)-benzoic acid methyl ester;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-indan-1-yl}-amide;

(rac)-2-Chloro-6-(1-{[1-(2,2,2-trifluoro-acetylamino)-cyclopropanecarbonyl]-amino}-indan-5-yl)-benzoic acid methyl ester;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

2-Chloro-6-((S)-1-{[3-(2,2,2-trifluoro-acetylamino)-oxetane-3-carbonyl]-amino}-indan-5-yl)-benzoic acid methyl ester;

3-(2,2,2-Trifluoro-acetylamino)-oxetane-3-carboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

3-(2,2,2-Trifluoro-acetylamino)-oxetane-3-carboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-indan-1-yl}-amide;

and pharmaceutically-acceptable salts thereof.

20. A compound according to claim 1 , selected from the group consisting of

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl-}amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-yl-}amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-1-methyl-indan-1-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-1-methyl-indan-1-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzofuran-3-yl}-amide;

and pharmaceutically acceptable salts thereof.

21. A compound according to claim 1 , selected from the group consisting of

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-yl}-amide;

(1-{(S)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

1-Amino-cyclopropanecarboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

Pyrimidine-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

Pyridazine-4-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

Isoxazole-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

5-Methyl-[1,3,4]oxadiazole-2-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

and pharmaceutically acceptable salts thereof.

22. A compound according to claim 1 , selected from the group consisting of

(1-{(rac)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

1-Amino-cyclopropanecarboxylic acid{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-yl}-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

Pyridazine-4-carboxylic acid(1-{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

(1-{(rac)-3-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

1-Amino-cyclopropanecarboxylic acid{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl}-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

Pyridazine-4-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

and pharmaceutically acceptable salts thereof.

23. A compound according to claim 1 , selected from the group consisting of

Pyridazine-4-carboxylic acid(1-{(S or R)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

Isoxazole-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

(1-{(rac)-6-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

1-Amino-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-yl}-amide;

Pyridazine-4-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-ylcarbamoyl}-cyclopropyl)-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-2,3-dihydro-benzofuran-3-ylcarbamoyl}-cyclopropyl)-amide;

3-Amino-oxetane-3-carboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

Pyrimidine-5-carboxylic acid (3-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-amide;

and pharmaceutically acceptable salts thereof.

24. A compound according to claim 1 , selected from the group consisting of

Isoxazole-5-carboxylic acid (3-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-amide;

3-Methyl-isoxazole-5-carboxylic acid (3-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid (3-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-amide;

(1-{(rac)-3-[5-Chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

1-Amino-cyclopropanecarboxylic acid{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl}-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

Isoxazole-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

3-Methyl-isoxazole-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(rac)-3-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-ylcarbamoyl}-cyclopropyl)-amide;

(1-{(rac)-6-[5-Chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-ylcarbamoyl}-cyclopropyl)-carbamic acid tert-butyl ester;

and pharmaceutically acceptable salts thereof.

25. A compound according to claim 1 , selected from the group consisting of

1-Amino-cyclopropanecarboxylic acid{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-yl}-amide;

5-Methyl-[1,3,4]oxadiazole-2-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-ylcarbamoyl}-cyclopropyl)-amide;

Pyrimidine-5-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-ylcarbamoyl}-cyclopropyl)-amide;

Isoxazole-5-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(rac)-6-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)-phenyl]-2,3-dihydro-benzo[b]thiophen-3-ylcarbamoyl}-cyclopropyl)-amide;

and pharmaceutically acceptable salts thereof.

26. A compound according to claim 1 , selected from the group consisting of

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl}-amide;

1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid{(rac)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-7-fluoro-indan-1-yl}-amide;

2-Methoxy-pyrimidine-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4] oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

Pyridazine-4-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

3-Methoxy-isoxazole-5-carboxylic acid(1-{(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-cyclopropyl)-amide;

and pharmaceutically acceptable salts thereof.

27. A compound according to claim 1 , selected from the group consisting of