US2020339570A1PendingUtilityA1

Bicyclic derivatives

Assignee: HOFFMANN LA ROCHEPriority: Sep 25, 2012Filed: Mar 13, 2020Published: Oct 29, 2020
Est. expirySep 25, 2032(~6.2 yrs left)· nominal 20-yr term from priority
C07D 413/12A61P 1/16C07D 487/04A61P 25/00C07D 471/04C07D 519/00C07D 403/12A61P 37/06A61P 13/12
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Claims

Abstract

wherein R1, Y, A, W, R2, m, n, p and q are as described herein, compositions including the compounds and methods of using the compounds.

Claims

exact text as granted — not AI-modified
1 - 57 . (canceled) 
     
     
         58 . A compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenyl alkenyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, or substituted 1H-indol-2-yl, wherein the substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkenyl, substituted naphthyl, substituted quinolinyl, substituted isoquinolinyl, and substituted 1H-indol-2-yl are substituted with R 8 , R 9 , and R 10 ; 
 Y is —OC(O)—, —NR 7 C(O)—, or —C(O)—; 
 A is —N— or CR 5 —; 
 W is —O—, —NR 6 —, —C(O)—, —S(O) 2 —, —C(O)—NR 6 —, or —CR 3 R 4 —; 
 R 3  and R 4  are independently H, halogen, alkyl, or cycloalkyl; 
 R 5 , R 6 , and R 7  are independently H, alkyl, or cycloalkyl; 
 R 8 , R 9 , and R 10  are independently H, alkyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyhaloalkyl, alkoxyalkoxy, alkoxyalkoxyalkyl, phenyl, substituted phenyl, halogen, hydroxy, cyano, alkylsulfanyl, haloalkylsulfanyl, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, substituted aminosulfonyl, substituted amino, or 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 is substituted with one to three substituents independently selected from alkyl, halogen, haloalkyl, alkoxy, and haloalkoxy; 
 
 m, n, p, and q are each independently 1 or 2; 
 R 2  is the ring system B, C, E, G, H, L, M, O, P, R, S, T, U, V, X, Z, AA, AB, AC, AD, AE, AG, AH, AI, or AJ: 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         R 11  is H, alkyl, haloalkyl, or cycloalkyl; and 
         R 12  is alkyl, halogen, haloalkyl, or alkoxy. 
       
     
     
         59 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein:
 R 2  is ring system B, C, E, G, H, L, M, O, P, R, S, T, U, V, X, Z, AA, AB, AC, AD, or AE; and   R 1  is substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkenyl, or substituted 1H-indol-2-yl, wherein the substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkenyl, or substituted 1H-indol-2-yl is substituted with R 8 , R 9 , and R 10 .   
     
     
         60 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 1  is substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkenyl, or substituted 1H-indol-2-yl, wherein the substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkenyl, or substituted 1H-indol-2-yl is substituted with R 8 , R 9 , and R 10 . 
     
     
         61 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 1  is substituted phenylalkyl or substituted phenylalkenyl, wherein the substituted phenylalkyl or substituted phenylalkenyl is substituted with R 8 , R 9 , and R 10 . 
     
     
         62 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 1  is phenylalkyl substituted with R 8 , R 9 , and R 10 . 
     
     
         63 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein Y is —OC(O)— or —C(O)—. 
     
     
         64 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein Y is —OC(O)—. 
     
     
         65 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein Y is —C(O)—. 
     
     
         66 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein A is —N—. 
     
     
         67 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein W is —C(O)—, —C(O)—NR 6 — or —CR 3 R 4 —. 
     
     
         68 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein W is —C(O)—. 
     
     
         69 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 2  is ring system B, H, M, O, R, and AJ. 
     
     
         70 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 2  is ring system B, H, O, and R. 
     
     
         71 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 2  is ring system B. 
     
     
         72 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 3  and R 4  are H. 
     
     
         73 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 6  is H or alkyl. 
     
     
         74 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 8 , R 9 , and R 10  are independently selected from H, alkyl, haloalkyl, hydroxyhaloalkyl, alkoxy, haloalkoxy, alkoxyhaloalkyl, phenyl, halogen, cyano, haloalkylsulfanyl, haloalkylsulfinyl, alkyl sulfonyl, 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. 
     
     
         75 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 8 , R 9 , and R 10  are independently selected from H, alkyl, haloalkyl, haloalkoxy, halogen, and alkylsulfonyl. 
     
     
         76 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 8  is haloalkyl, haloalkoxy, halogen or alkylsulfonyl. 
     
     
         77 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 8  is haloalkoxy or halogen. 
     
     
         78 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 9  is H, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cyano, or halogen. 
     
     
         79 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 9  is H, alkyl, haloalkyl, alkoxy, or halogen. 
     
     
         80 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 9  is H, alkyl, or halogen. 
     
     
         81 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 8  and R 9  are halogen. 
     
     
         82 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 10  is H, alkyl, alkoxy or halogen. 
     
     
         83 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 10  is H or alkyl. 
     
     
         84 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein R 11  is haloalkyl. 
     
     
         85 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein m and n are 1. 
     
     
         86 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein p and q are 1. 
     
     
         87 . The compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, wherein m, n, p, and q are 1. 
     
     
         88 . A compound, wherein the compound is:
 6-((3aR,6aS)-5-(3-(3,5-dichlorophenyl)propanoyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzo[d]oxazol-2(3H)-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-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-3H-benzooxazol-2-one;   (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)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   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;   (3aSR,6SR,7aSR)-6-{(3aS,8aR)-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-hexahydro-benzooxazol-2-one;   (3aR,6aS)-3,5-dichlorobenzyl 5-(9H-pyrido[3,4-b]indole-3-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-(1H-indole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-(9H-carbazole-3-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-(1H-indazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-((1H-indazol-5-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-(1H-benzo[d]imidazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aR,6aS)-3,5-dichlorobenzyl 5-((1H-benzo[d]imidazol-5-yl)methyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (E)-1-[(3aS,8aR)-2-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridine-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one;   (E)-1-[(3aS,8aR)-2-(4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one;   (E)-1-[(3aS,8aR)-2-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one (3aR,6aS)-3,5-dichlorobenzyl 5-(4,5,6,7-tetrahydro-1H-benzo[d][1,2,3]triazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   (3aS,6aS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-cyano-2-isopropyl-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-cyano-2-isopropyl-5-methyl-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 2-fluoro-4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 3-fluoro-4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-Tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-Tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethyl-benzyl ester;   (3aS,6aS)-5-((R)-4,5,6,7-Tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 3-chloro-5-methanesulfonyl-benzyl ester;   (E)-1-[(3aS,8aR)-2-((S)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one   (E)-1-((3aR,6aS)-5-(4,5,6,7-tetrahydro-1H-benzo[d][1,2,3]triazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-one;   (4-ethoxyquinolin-2-yl)((3aS,6aS)-5-((R)-4,5,6,7-tetrahydro-1H-benzo[d][1,2,3]triazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone;   (E)-1-[(3aS,6aS)-5-((R)-4,5,6,7-Tetrahydro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propenone;   1-((3aR,6aR)-5-((R)-4,5,6,7-tetrahydro-1H-benzo[d][1,2,3]triazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(4-(trifluoromethoxy)phenyl)propan-1-one;   [(3aS,6aS)-5-(4′-Chloro-biphenyl-4-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(R)-4,5,6,7-tetrahydro-1H-benzotriazol-5-yl-methanone;   [(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(4-propan-2-yloxynaphthalen-2-yl)methanone;   [(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(4-propan-2-yloxyquinolin-2-yl)methanone;   1-[(3aR,6aR)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[2-fluoro-4-(trifluoromethoxy)phenyl]propan-1-one;   4-[2-[(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-oxoethoxy]-2-methyl-5-propan-2-ylbenzonitrile;   [(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-[1-(2,2,2-trifluoroethoxy)isoquinolin-3-yl]methanone;   1-[(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-(4-bromo-2-tert-butylphenoxy)ethanone;   4-[2-[(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-oxoethoxy]-3-tert-butylbenzonitrile;   [(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-[1-methyl-5-(trifluoromethoxy)indol-2-yl]methanone;   1-[(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-2-[4-(trifluoromethoxy)phenoxy]ethanone;   [(3aS,6aS)-5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(1-ethoxyisoquinolin-3-yl)methanone;   (E)-1-[(3aS,8aR)-2-(benzo[c][1,2,5]oxadiazole-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one;   (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 4-trifluoromethoxy-benzyl ester;   (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-ene-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-ene-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-ene-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;   (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-ene-1-one;   (3aR,7aR)-5-{(3aR,6aR)-5-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carbonyl}-hexahydro-oxazol o[5,4-c]pyridin-2-one;   (3aR,7aR)-5-{(3aR,6aR)-5-[3-(4-trifluoromethoxy-phenyl)-propionyl]-hexahydro-pyrrolo[3,4-c]pyrrole-2-carbonyl}-hexahydro-oxazol o[5,4-c]pyridin-2-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;   6-{(3aS,8aR)-6-[(E)-3-(4-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-2-carbonyl}-5,6,7,8-tetrahydro-1H-[1,6]naphthyridin-2-one;   (E)-1-[(3aS,8aR)-2-(7,8-Dihydro-5H-[1,6]naphthyridine-6-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one;   (E)-3-(4-trifluoromethoxy-phenyl)-1-[(3aS,8aR)-2-(2-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-prop-2-ene-1-one;   (3aR,5 S,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;   (3aS,8aR)-6-[(E)-3-(3-trifluoromethoxy-phenyl)-acryloyl]-octahydro-pyrrolo[3,4-d]azepine-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-(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)-carb oxamide;   (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,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-methyl 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;   (E)-1-[(3aS,8aR)-2-(6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazine-5-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-3-(4-trifluoromethoxy-phenyl)-prop-2-ene-1-one;   (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;   (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;   (E)-3-[4-(trifluoro-methoxy)-phenyl]-1-[(3aS,8aR)-2-((S)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carbonyl)-octahydro-pyrrolo[3,4-d]azepin-6-yl]-prop-2-ene-1-one hydrochloride;   (3aS,6aS)-5-(3H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   1-[(3aR,6aR)-5-(1H-triazolo[4,5-b]pyridine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[4-(trifluoromethoxy)phenyl]propan-1-one;   (3aS,6aS)-5-(1H-[1,2,3]triazolo[4,5-b]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 3-fluoro-4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(1H-[1,2,3]triazolo[4,5-b]pyridine-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(3H-[1,2,3]triazolo[4,5-c]pyridine-6-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(4-fluoro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(7-fluoro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(6-fluoro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(4-chloro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(6-trifluoromethyl-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(4-methyl-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   (3aS,6aS)-5-(6-methyl-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   1-[(3aR,6aR)-5-(4-fluoro-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propan-1-one;   (4-ethoxyquinolin-2-yl)((3aS,6aS)-5-(4-fluoro-1H-benzo[d][1,2,3]triazole-5-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone;   (3aS,6aS)-5-(4-methoxy-1H-benzotriazole-5-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester; or   (3aS,6aS)-5-(4-sulfamoyl-piperidine-1-carbonyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid 4-trifluoromethoxy-benzyl ester;   or a pharmaceutically acceptable salt thereof.   
     
     
         89 . A process to prepare a compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, the process comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III), wherein R 1 , R 2 , A, W, m, n, p and q are as defined for formula (I), and Y is —OC(O)—: 
       
         
           
           
               
               
           
         
       
     
     
         90 . A pharmaceutical composition, comprising a compound according to  claim 58 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier. 
     
     
         91 . A pharmaceutical composition, comprising a compound according to  claim 88 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier. 
     
     
         92 . A method of treating a condition, comprising administering an effective amount of a compound of  claim 58 , or a pharmaceutically acceptable salt thereof, and wherein the condition is selected from the group consisting of renal conditions, liver conditions, inflammatory conditions, conditions of the nervous system, conditions of the respiratory system, vascular and cardiovascular conditions, fibrotic diseases, ocular conditions, metabolic conditions, and acute and chronic organ transplant rejection. 
     
     
         93 . A method of treating a condition, comprising administering an effective amount of a compound of  claim 88 , or a pharmaceutically acceptable salt thereof, and wherein the condition is selected from the group consisting of renal conditions, liver conditions, inflammatory conditions, conditions of the nervous system, conditions of the respiratory system, vascular and cardiovascular conditions, fibrotic diseases, ocular conditions, metabolic conditions, and acute and chronic organ transplant rejection.

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