New bicyclic compounds as atx inhibitors

Abstract

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

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is substituted phenyl, substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted phenyl-C 2-6 -alkynyl, substituted pyridinyl, substituted pyridinyl-C 1-6 -alkyl, substituted pyridinyl-C 2-6 -alkenyl, substituted pyridinyl-C 2-6 -alkynyl, substituted thiophenyl, substituted thiophenyl-C 1-6 -alkyl, substituted thiophenyl-C 2-6 -alkenyl or substituted thiophenyl-C 2-6 -alkynyl, wherein substituted phenyl, substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted phenyl-C 2-6 -alkynyl, substituted pyridinyl, substituted pyridinyl-C 1-6 -alkyl, substituted pyridinyl-C 2-6 -alkenyl, substituted pyridinyl-C 2-6 -alkynyl, substituted thiophenyl, substituted thiophenyl-C 1-6 -alkyl, substituted thiophenyl-C 2-6 -alkenyl and substituted thiophenyl-C 2-6 -alkynyl are substituted by R 3 , R 4  and R 5 ; 
 Y is —OC(O)— or —C(O)—; 
 W is —C(O)—, —S(O) 2 — or —CR 6 R 7 —; 
 R 2  is selected from the ring systems B, F, L, M, O, Z, AF, AG, AH, AJ, AN, AO, AP, AQ, AR, AS, AT, AU, AV, AW, AX, AY, AZ, BA, BC and BD; 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         R 3  is halogen, hydroxy, cyano, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3- -cycloalkyl-C 1-6 -alkoxy, C 3- -cycloalkoxy, C 3-8 -cycloalkoxy-C 1-6 -alkyl, C 1-6 -alkylamino, C 1-6 -alkylcarbonylamino, C 3-8 -cycloalkylcarbonylamino, C 1-6 -alkyltetrazolyl, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or heterocycloalkyl-C 1-6 -alkoxy; 
         R 4  and R 5  are independently selected from H, halogen, hydroxy, cyano, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 3- -cycloalkyl, C 3- -cycloalkyl-C 1-6 -alkyl, C 3- -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy, C 3- -cycloalkoxy-C 1-6 -alkyl, C 1-6 -alkylcarbonylamino, C 3-8 -cycloalkylcarbonylamino, C 1-6 -alkyltetrazolyl, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or heterocycloalkyl-C 1-6 -alkoxy; 
         R 6  is H or C 1-6 -alkyl; 
         R 7  is H, C 1-6 -alkyl, halogen, halo-C 1-6 -alkyl or C 1-6 -alkoxy; 
         m, n, p and q are independently selected from 1 and 2; and 
         r is 1, 2 or 3; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A compound according to  claim 1 , wherein
 R 1  is substituted phenyl, substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted phenyl-C 2-6 -alkynyl, substituted pyridinyl, substituted pyridinyl-C 1-6 -alkyl, substituted pyridinyl-C 2-6 -alkenyl, substituted pyridinyl-C 2-6 -alkynyl, substituted thiophenyl, substituted thiophenyl-C 1-6 -alkyl, substituted thiophenyl-C 2-6 -alkenyl or substituted thiophenyl-C 2-6 -alkynyl, wherein substituted phenyl, substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted phenyl-C 2-6 -alkynyl, substituted pyridinyl, substituted pyridinyl-C 1-6 -alkyl, substituted pyridinyl-C 2-6 -alkenyl, substituted pyridinyl-C 2-6 -alkynyl, substituted thiophenyl, substituted thiophenyl-C 1-6 -alkyl, substituted thiophenyl-C 2-6 -alkenyl and substituted thiophenyl-C 2-6 -alkynyl are substituted by R 3 , R 4  and R 5 ;   Y is —OC(O)— or —C(O)—;   W is —C(O)—, —S(O) 2 — or —CR 6 R 7 —;   R 2  is selected from the ring systems B, F, L, M, O, Z, AF, AG, AH, AJ, AN, AO, AP, AQ, AR, AS, AT, AU and AV;   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         R 3  is halogen, hydroxy, cyano, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 3- -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3- -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy, C 3-8 -cycloalkoxy-C 1-6 -alkyl, C 1-6 -alkylamino, C 1-6 -alkylcarbonylamino, C 3-8 -cycloalkylcarbonylamino, C 1-6 -alkyltetrazolyl, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or heterocycloalkyl-C 1-6 -alkoxy; 
         R 4  and R 5  are independently selected from H, halogen, hydroxy, cyano, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 3- -cycloalkyl, C 3- -cycloalkyl-C 1-6 -alkyl, C 3- -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy, C 3- -cycloalkoxy-C 1-6 -alkyl, C 1-6 -alkylcarbonylamino, C 3-8 -cycloalkylcarbonylamino, C 1-6 -alkyltetrazolyl, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl and heterocycloalkyl-C 1-6 -alkoxy; 
         R 6  is H or C 1-6 -alkyl; 
         R 7  is H, C 1-6 -alkyl, halogen, halo-C 1-6 -alkyl or C 1-6 -alkoxy; 
         m, n, p and q are independently selected from 1 and 2; and 
         r is 1, 2 or 3; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . A compound according to  claim 1 , wherein
 R 1  is substituted phenyl-C 1-6 -alkyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4  and R 5 ;   Y is —OC(O)— or —C(O)—;   W is —C(O)— or CR 6 R 7 ;   R 2  is selected from the ring systems M, O, Z, AJ, AN, AO, AP, AW, AX, AY, AZ, B, BA, BB, BC and BD;   R 3  is halo-C 1-6 -alkoxy, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or tetrahydropyranyl-C 1-6 -alkoxy;   R 4  is H, halogen, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl;   R 5  is H or halogen;   R 6  is H or C 1-6 -alkyl;   R 7  is H;   m, n, p and q are 1; and   r is 1;   or a pharmaceutically acceptable salt thereof.   
     
     
         4 . A compound according to  claim 1 , wherein
 R 1  is substituted phenyl-C 1-6 -alkyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4  and R 5 ;   Y is —OC(O)— or —C(O)—;   W is —C(O)—;   R 2  is selected from the ring systems M, O, Z, AJ, AN and AO;   R 3  is halo-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or tetrahydropyranyl-C 1-6 -alkoxy;   R 4  is H, halogen, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl;   R 5  is H;   R 6  is C 1-6 -alkyl;   R 7  is H;   m, n, p and q are 1; and   r is 1;   or a pharmaceutically acceptable salt thereof.   
     
     
         5 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  substituted phenyl-C 1-6 -alkyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4  and R 5 . 
     
     
         6 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is pyridinyl or pyridinyl-C 1-6 -alkyl substituted by R 3 , R 4  and R 5 . 
     
     
         7 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is —OC(O)—. 
     
     
         8 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is is selected from the ring systems M, O, Z, AJ, AN, AO, AP, AW, AX, AY, AZ, B, BA, BB, BC and BD. 
     
     
         9 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is is selected from the ring systems M, O, Z, AJ, AN and AO. 
     
     
         10 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is selected from the ring systems M, AJ and AO. 
     
     
         11 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is halo-C 1-6 -alkoxy, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or tetrahydropyranyl-C 1-6 -alkoxy. 
     
     
         12 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is halo-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or tetrahydropyranyl-C 1-6 -alkoxy. 
     
     
         13 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is C 1-6 -alkylcarbonylamino, or tetrahydropyranyl-C 1-6 -alkoxy. 
     
     
         14 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is H, halogen, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl. 
     
     
         15 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is halo-C 1-6 -alkyl or C 3-8 -cycloalkyl. 
     
     
         16 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5  is H or halogen. 
     
     
         17 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5  is H. 
     
     
         18 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6  is H or C 1-6 -alkyl. 
     
     
         19 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6  is C 1-6 -alkyl. 
     
     
         20 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7  is H. 
     
     
         21 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein m, n, p and q are 1. 
     
     
         22 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein r is 1. 
     
     
         23 . A compound according to  claim 1 , wherein
 R 1  is pyridinyl or pyridinyl-C 1-6 -alkyl substituted by R 3 , R 4  and R 5 ;   Y is —OC(O)—;   W is —C(O)—;   R 2  is selected from the ring systems M, AJ and AO;   R 3  is C 1-6 -alkylcarbonylamino or tetrahydropyranyl-C 1-6 -alkoxy;   R 4  is halo-C 1-6 -alkyl or C 3-8 -cycloalkyl;   R 5  is H;   R 7  is H; and   m, n, p and q are 1;   or a pharmaceutically acceptable salt thereof.   
     
     
         24 . A compound according to  claim 1 , selected from
 [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   6-(5-(2-cyclopropyl-6-((tetrahydro-2H-pyran-4-yl)methoxy)isonicotinoyl)-1,2,3,4,5,6-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl)-1-methyl-1H-benzo[d]imidazol-2(3H)-one;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(1,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(1H-benzotriazole-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   4-(trifluoromethoxy)benzyl 5-(1H-benzo[d][1,2,3]triazole-5-carbonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   1-[5-(1H-benzotriazole-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[2-[(5-methyltetrazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propan-1-one;   [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 6-(1H-benzotriazole-5-carbonyl)-1,3,4,5,7,8-hexahydro-2,6-naphthyridine-2-carboxylate;   [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(1,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(1,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate; and   (1H-1,2,3-triazol-4-yl)methyl 5-(2-cyclopropyl-6-((tetrahydro-2H-pyran-4-yl)methoxy)isonicotinoyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;   or a pharmaceutically acceptable salt thereof thereof.   
     
     
         25 . A compound according to  claim 1 , selected from
 [5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(1H-benzotriazole-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   [5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]-(3-hydroxy-1,2-benzoxazol-6-yl)methanone;   6-[5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carbonyl]-1,1-dioxo-1,2-benzothiazol-3-one;   1-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]piperidine-4-sulfonamide;   [5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-hydroxy-5,7-dihydro-4H-[,2]oxazolo[5,4-c]pyridine-6-carbonyl)-,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;   7-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-2,5,6,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-one;   6-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-2,5,7,8-tetrahydropyrido[3,4-d]pyridazin-1-one;   [2-cyclopropyl-6-(2,2,2-trifluoroethoxy)pyridin-4-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   1-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]-3-[2-[(5-methyltetrazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propan-1-one;   [5-cyclopropyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(3-hydroxy-2,4,5,7-tetrahydropyrazolo[3,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(3-hydroxy-6,7-dihydro-4H-[1,2]oxazolo[4,5-c]pyridine-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   7-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-5,6,8,8a-tetrahydroimidazo[1,5-a]pyrazine-1,3-dione;   [2-(cyclohexylmethoxy)-6-cyclopropylpyridin-4-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   1-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-3,4,5,6-tetrahydro-1H-cyclopenta[c]pyrrole-5-carbonyl]piperidine-4-sulfonamide;   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(1,4,6,7-tetrahydrotriazolo[4,5-c]pyridine-5-carbonyl)-3,4,5,6-tetrahydro-1 #H!-cyclopenta[c]pyrrol-2-yl]methanone;   6-[[5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methyl]-3H-1,3-benzoxazol-2-one;   1-[2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-4-fluoropiperidine-4-sulfonamide; and   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-3,4,5,6-tetrahydro-1H-cyclopenta[c]pyrrol-2-yl]methanone;   or a pharmaceutically acceptable salt thereof thereof.   
     
     
         26 . A compound according to  claim 1 , selected from
 [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-[(5R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(1H-benzotriazole-5-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate; and   [2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridin-4-yl]-[5-(3-hydroxy-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridine-6-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrol-2-yl]methanone;   or a pharmaceutically acceptable salt thereof thereof.   
     
     
         27 . A process to prepare a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III), 
       
         
           
           
               
               
           
         
         wherein W is —C(O)—. 
       
     
     
         28 . (canceled) 
     
     
         29 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier. 
     
     
         30 .- 32 . (canceled) 
     
     
         33 . A method for the treatment or prophylaxis ocular conditions, which method comprises administering an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         34 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, when manufactured according to a process of  claim 27 . 
     
     
         35 . (canceled)