New bicyclic derivatives

Abstract

The invention provides novel compounds having the general formula (I) wherein R 1 , Y, A, W, R 2 , m, n, p and q are as described herein, compositions including the compounds and methods of using the compounds.

1 . A Compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is alkyl, haloalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted phenylalkynyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, naphtyl, substituted naphthyl, quinolyl, substituted quinolinyl, isoquinolyl, substituted isoquinolinyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl or substituted benzofuran-2-yl wherein substituted cycloalkyl, substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenylalkyl, substituted phenylalkynyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl and substituted benzofuran-2-yl are substituted with R 8 , R 9  and R 10 ; 
         R 2  is: 
       
       
         
           
           
               
               
           
         
         Y is —OC(O)—, —NR 7 C(O)—, —C(O)—, —S(O) 2 —, 
       
       
         
           
           
               
               
           
         
         A is —N— or CR 5 —; 
         W is —O—, —S—, —NR 6 —, —C(O)—, —S(O) 2 —, —C(O)—NR 6 — or —CR 3 R 4 —; 
         R 3  and R 4  are independently selected from H, halogen, alkyl and cycloalkyl; 
         R 5 , R 6  and R 7  are independently selected from H, alkyl and cycloalkyl; 
         R 8 , R 9  and R 10  are independently selected from H, alkyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkoxy, cycloalkoxyalkyl, cycloalkylalkoxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyhaloalkyl, alkoxyalkoxy, alkoxyalkoxyalkyl, phenyl, substituted phenyl, pyridinyl, substituted pyridinyl, pyrrolyl, substituted pyrrolyl, pyrrolydinyl, substituted pyrrolydinyl, tetrahydrofuranyl, substituted tetrahydrofuranyl, halogen, hydroxy, cyano, alkylsulfanyl, haloalkylsulfanyl, cycloalkylsulfanyl, alkylsulfinyl, haloalkylsulfinyl, cycloalkylsulfinyl, alkylcarbonyl, haloalkylcarbonyl, cycloalkylcarbonyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, substituted aminosulfonyl, substituted amino and substituted aminoalkyl, wherein substituted aminosulfonyl, substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl and cycloalkylcarbonyl, and wherein substituted phenyl, substituted pyrrolyl, substituted pyrrolydinyl, substituted tetrahydrofuranyl, and substituted pyridinyl are substituted with one to three substituents independently selected from alkyl, halogen, haloalkyl, alkoxy and haloalkoxy; 
         m, n, p and q are independently selected from 1 or 2; 
         R 11  is H, alkyl, haloalkyl or cycloalkyl; 
         R 12  is alkyl, halogen, haloalkyl and alkoxy; 
         R 2  is selected from the ring systems B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, X, Z, AA, AB, AC, AD, AE, AF, AG, AH, AI and AJ; 
         and pharmaceutically acceptable salts thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein:
 R 1  is alkyl, haloalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted phenylalkynyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl or substituted benzofuran-2-yl wherein substituted cycloalkyl, substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenylalkynyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted pyridinylalkynyl, substituted thiophenyl, substituted thiophenylalkyl, substituted thiophenylalkenyl, substituted thiophenylalkynyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl and substituted benzofuran-2-yl are substituted with R 8 , R 9  and R 10 .   
     
     
         3 . The compound of  claim 1 , wherein:
 R 1  is substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, naphtyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, or substituted 1H-indol-2-yl, wherein substituted cycloalkylalkyl, substituted piperazinyl, substituted piperidinyl, substituted indanyloxyalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl and substituted 1H-indol-2-yl are substituted with R 8 , R 9  and R 10 .   
     
     
         4 . The compound of  claim 1 , wherein:
 R 1  is substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted pyridinylalkenyl or substituted 1H-indol-2-yl, wherein substituted cycloalkylalkyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted pyridinylalkenyl, and substituted 1H-indol-2-yl are substituted with R 8 , R 9  and R 10 .   
     
     
         4 . The compound of  claim 1 , wherein:
 R 1  is substituted phenylalkyl or substituted phenylalkenyl, wherein substituted phenylalkyl and substituted phenylalkenyl are substituted with R 8 , R 9  and R 10 .   
     
     
         5 . The compound of  claim 1 , wherein R 1  is phenylalkyl substituted with R 8 , R 9  and R 10 . 
     
     
         6 . The compound of  claim 1 , wherein Y is —OC(O)—, —C(O)—, —S(O) 2 — or 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1 , wherein Y is —OC(O)— or —C(O)—. 
     
     
         8 . The compound of  claim 1 , wherein Y is —OC(O)—. 
     
     
         9 . The compound of  claim 1 , wherein Y is —C(O)—. 
     
     
         10 . The compound of  claim 1 , wherein A is —N—. 
     
     
         11 . The compound of  claim 1 , wherein W is —O—, —NR 6 —, —C(O)—, —S(O) 2 —, —C(O)—NR 6 — or —CR 3 R 4 —. 
     
     
         12 . The compound of  claim 1 , wherein W is —C(O)—, —C(O)—NR 6 — or —CR 3 R 4 —. 
     
     
         13 . The compound of  claim 1 , wherein W is —C(O)—. 
     
     
         14 . The compound of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 1 , wherein R 3  and R 4  are H. 
     
     
         19 . The compound of  claim 1 , wherein R 5  is H. 
     
     
         20 . The compound of  claim 1 , wherein R 6  is H or alkyl. 
     
     
         21 . The compound of  claim 1 , wherein R 8 , R 9  and R 10  are independently selected from H, alkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, haloalkoxy, alkoxyhaloalkyl, phenyl, pyridinyl, halogen, cyano, haloalkylsulfanyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, pyrrolyl substituted with one alkyl, pyrrolydinyl, tetrahydrofuranyl, alkylcarbonyl, and aminosulfonyl substituted on the nitrogen atom with one to two substituents independently selected from H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl and cycloalkylcarbonyl. 
     
     
         22 . The compound of  claim 1 , wherein R 8 , R 9  and R 10  are independently selected from H, alkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, haloalkoxy, alkoxyhaloalkyl, phenyl, pyridinyl, halogen, cyano, haloalkylsulfanyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl substituted on the nitrogen atom with one to two substituents independently selected from H, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl and cycloalkylcarbonyl. 
     
     
         23 . The compound of  claim 1 , wherein R 8 , R 9  and R 10  are independently selected from H, alkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, haloalkoxy, alkoxyhaloalkyl, phenyl, pyridinyl, halogen, cyano, haloalkylsulfanyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl and aminosulfonyl substituted on the nitrogen atom with two alkyl. 
     
     
         24 . The compound of  claim 1 , wherein R 8 , R 9  and R 10  are independently selected from H, alkyl, haloalkyl, haloalkoxy, halogen and alkylsulfonyl. 
     
     
         25 . The compound of  claim 1 , wherein R 8  is H, alkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, haloalkoxy, alkoxyhaloalkyl, phenyl, pyridinyl, halogen, cyano, haloalkylsulfanyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, pyrrolyl substituted with one alkyl, pyrrolydinyl, tetrahydrofuranyl, alkylcarbonyl, or aminosulfonyl substituted on the nitrogen atom with two alkyl. 
     
     
         26 . The compound of  claim 1 , wherein R 8  is haloalkyl, haloalkoxy, halogen or alkylsulfonyl. 
     
     
         27 . The compound of  claim 1 , wherein R 8  is haloalkoxy or halogen. 
     
     
         28 . The compound of  claim 1 , wherein R 8  is halogen. 
     
     
         29 . The compound of  claim 1 , wherein R 9  is H, alkyl, haloalkyl, cycloalkyl, cycloalkoxy, alkoxy, haloalkoxy, alkoxyalkoxy, cyano or halogen. 
     
     
         30 . The compound of  claim 1 , wherein R 9  is H, alkyl, haloalkyl, alkoxy or halogen. 
     
     
         31 . The compound of  claim 1 , wherein R 9  is H, alkyl or halogen. 
     
     
         32 . The compound of  claim 1 , wherein R 8  and R 9  are halogen. 
     
     
         33 . The compound of  claim 1 , wherein R 10  is H, alkyl, alkoxy or halogen. 
     
     
         24 . The compound of  claim 1 , wherein R 10  is H or alkyl. 
     
     
         25 . The compound of  claim 1 , wherein R 10  is H. 
     
     
         26 . The compound of  claim 1 , wherein R 11  is haloalkyl. 
     
     
         37 . The compound of  claim 1 , wherein m is 1. 
     
     
         38 . The compound of  claim 1 , wherein n is 1. 
     
     
         39 . The compound of  claim 1 , wherein m and n are 1. 
     
     
         40 . The compound of  claim 1 , wherein p and q are 1. 
     
     
         41 . The compound of  claim 1 , wherein m, n, p and q are 1. 
     
     
         42 . The compound of  claim 1 , selected from:
 6-((3aR,6aS)-5-(3-(3,5-dichlorophenyl)propanoyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzo[d]oxazol-2(3H)-one;   (3aSR,6 SR,7aSR)-6-{(3aR,8aS)-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-hexahydro-benzooxazol-2-one;   trans-3,5-Dichlorobenzyl 2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-carbonyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5 (6H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   6-{(3aS,8aR)-6-[(E)-3-(4-trifluoromethxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-3H-benzooxazol-2-one;   6-[(3aR,6aR)-2-[3-[4-(trifluoromethoxy)phenyl]propanoyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-3H-1,3-benzoxazol-2-one;   (3aS,6aS)-5-(2-oxo-2,3-dihydro-benzooxazole-6-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aR,5s,6aS)-3,5-Dichlorobenzyl 5-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yloxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate;   (3aR,5r,6aS)-3,5-Dichlorobenzyl 5-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yloxy)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate;   (3aR,5r,6aS)-3,5-Dichlorobenzyl 5-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-ylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-((2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   6-(((3aR,6aS)-5-(3-(3,5-dichlorophenyl)propanoyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methyl)benzo[d]oxazol-2(3H)-one;   (3aR,6aS)-3,5-Dichlorobenzyl 5-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-ylsulfonyl)hexa-hydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,5s,6aS)-5-[(3H-[1,2,3]triazol-4-ylmethyl)-carbamoyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid 3,5-dichloro-benzyl ester;   (3aS,6aR)-5-[(1H-[1,2,3]triazol-4-ylmethyl)-carbamoyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 3,5-dichloro-benzyl ester;   (3aR,8aS)—N-((1H-1,2,3-Triazol-5-yl)methyl)-6-((E)-3-(4-(trifluoromethoxy)phenyl)-acryloyl)octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-6-((E)-3-(4-(trifluoromethoxy)phenyl)acryloyl)-octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aS,6aR)-5-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid (1H-[1,2,3]triazol-4-ylmethyl)-amide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-6-((E)-3-(3-fluoro-4-(trifluoromethoxy)phenyl)acryloyl)octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aS,8aR)-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carboxylic acid (4H-[1,2,4]triazol-3-ylmethyl)-amide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-N-methyl-6-((E)-3-(4-(trifluoromethoxy)phenyl)acryloyl)octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aS,8aR)-6-[3-(3-chloro-phenyl)-2,2-dimethyl-propionyl]-octahydro-pyrrolo[3,4-d]azepine-2-carboxylic acid (3H-[1,2,3]triazol-4-ylmethyl)-amide;   (3aR,8aS)—N-(2-(1H-1,2,3-triazol-5-yl)ethyl)-6-((E)-3-(4-(trifluoromethoxy)phenyl)acryloyl)-octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aR,6aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-N-methyl-5-(3-(4-(trifluoromethoxy)phenyl)propanoyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxamide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-6-((E)-3-(3-fluoro-4-(trifluoromethoxy)phenyl)acryloyl)-N-methyloctahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-N-methyl-6-(3-(4-(trifluoromethoxy)phenyl)-propanoyl)octahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aR,8aS)—N-((1H-1,2,3-triazol-5-yl)methyl)-6-(3-(3-fluoro-4-(trifluoromethoxy)phenyl)-propanoyl)-N-methyloctahydropyrrolo[3,4-d]azepine-2(1H)-carboxamide;   (3aS,8aR)-6-[3-(4-trifluoromethoxy-phenyl)-propionyl]-octahydro-pyrrolo[3,4-d]azepine-2-carboxylic acid [2-(3H-[1,2,3]triazol-4-yl)-ethyl]-amide;   (3aS,6aS)-5-(1,4,6,7-tetrahydro-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 3-chloro-5-methanesulfonyl-benzyl ester;   (3aR,6aS)-3,5-Dichlorobenzyl 5-(4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (E)-1-[(3aS,8aR)-2-(1,4,6,7-tetrahydro-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-en-1-one;   (E)-1-[(3aS,8aR)-2-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-en-1-one;   (E)-1-[(3aS,6aR)-5-(1,4,6,7-tetrahydro-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-en-1-one;   (E)-1-[(3aR,6aR)-5-(1,4,6,7-tetrahydro-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-en-1-one;   1-[(3aR,6aR)-5-(1,4,6,7-tetrahydro-[1,2,3]triazolo[4,5-c]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propan-1-one;   cis-5-((3aR,8aS)-6-((E)-3-(4-(trifluoromethoxy)phenyl)acryloyl)decahydropyrrolo[3,4-d]azepine-2-carbonyl)hexahydrooxazolo[5,4-c]pyridin-2(1H)-one;   (3aR,7aR)-5-{(3aS,8aR)-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-hexahydro-oxazolo[5,4-c]pyridin-2-one;   (3aR,7aR)-5-{(3aR,6aR)-5-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carbonyl}-hexahydro-oxazolo[5,4-c]pyridin-2-one; and   (3aR,7aR)-5-{(3aR,6aR)-5-[3-(4-trifluoromethoxy-phenyl)-propionyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carbonyl}-hexahydro-oxazolo[5,4-c]pyridin-2-one;   
     
     
         43 . A pharmaceutical composition comprising a compound of  claim 1  and a therapeutically inert carrier.