Bicyclic compounds as dual ATX/CA inhibitors
AssigneeHoffmann-La Roche Inc.
InventorsPatrick Di Giorgio, Jerome Hert, Daniel Hunziker, Patrizio Mattei, Markus Rudolph, Petra Schmitz, Christoph Ullmer
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Abstract
The invention provides novel compounds having the general formula (I) wherein R1, R2, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.
Claims36
A compound of formula (I)
- wherein
- R1 is substituted phenyl, substituted phenyl-C1-6-alkyl, substituted phenoxy-C1-6-alkyl, substituted phenyl-C2-6-alkenyl, substituted phenyl-C2-6-alkynyl, substituted quinolinyl, substituted quinolinyl-C1-6-alkyl, substituted quinolinyl-C1-6-alkenyl, substituted quinolinyl-C1-6-alkynyl, substituted pyridinyl, substituted pyridinyl-C1-6-alkyl, substituted pyridinyl-C2-6-alkenyl, substituted pyridinyl-C2-6-alkynyl, substituted thiophenyl, substituted thiophenyl-C1-6-alkyl, substituted thiophenyl-C2-6-alkenyl or substituted thiophenyl-C2-6-alkynyl, wherein substituted phenyl, substituted phenyl-C1-6-alkyl, substituted phenoxy-C1-6-alkyl, substituted phenyl-C2-6-alkenyl, substituted phenyl-C2-6-alkynyl, substituted quinolinyl, substituted quinolinyl-C1-6-alkyl, substituted quinolinyl-C1-6-alkenyl, substituted quinolinyl-C1-6-alkynyl, substituted pyridinyl, substituted pyridinyl-C1-6-alkyl, substituted pyridinyl-C2-6-alkenyl, substituted pyridinyl-C2-6-alkynyl, substituted thiophenyl, substituted thiophenyl-C1-6-alkyl, substituted thiophenyl-C2-6-alkenyl and substituted thiophenyl-C2-6-alkynyl are substituted by R3, R4 and R5;
- Y is —OC(O)— or —C(O)—;
- W is —C(O)—, —S(O)2— or —CR6R7—;
- R2 is substituted phenyl, substituted pyridinyl or substituted thiophenyl, wherein substituted phenyl, substituted pyridinyl and substituted thiophenyl are substituted by R6, R7 and R8;
- R3 is halogen, hydroxy, cyano, C1-6-alkyl, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, halo-C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C3-8-cycloalkyl-C1-6-alkoxy, C3-8-cycloalkoxy, C3-8-cycloalkoxy-C1-6-alkyl, C1-6-alkylamino, C1-6-alkylcarbonylamino, C3-8-cycloalkylcarbonylamino, C1-6-alkyltetrazolyl, C1-6-alkyltetrazolyl-C1-6-alkyl, heterocycloalkyl-C1-6-alkoxy or C1-6-alkylpiperidinyl-C1-6-alkoxy;
- R4 and R5 are independently selected from H, halogen, hydroxy, cyano, C1-6-alkyl, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, halo-C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C3-8-cycloalkyl-C1-6-alkoxy, C3-8-cycloalkoxy, C3-8-cycloalkoxy-C1-6-alkyl, C1-6-alkylcarbonylamino, C3-8-cycloalkylcarbonylamino, C1-6-alkyltetrazolyl, C1-6-alkyltetrazolyl-C1-6-alkyl and heterocycloalkyl-C1-6-alkoxy;
- R6 is aminosulfonyl;
- R7 and R8 are independently selected from H, halogen, hydroxy, cyano, C1-6-alkyl, C1-6-alkoxy, C1-6-alkoxy-C1-6-alkyl, halo-C1-6-alkoxy, halo-C1-6-alkyl, hydroxy-C1-6-alkyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C3-8-cycloalkyl-C1-6-alkoxy, C3-8-cycloalkoxy and C3-8-cycloalkoxy-C1-6-alkyl;
- and
- m, n, p and q are independently selected from 1 and 2;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a compound which is [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.
A pharmaceutical composition comprising a compound which is [3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(5-sulfamoylpyridine-2-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.
A compound, wherein the compound is:
- 3-fluoro-4-[2-[3-[2-[(4-methyltriazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
- or
- 3-fluoro-4-[2-[3[2-[(4-methyltriazol-1-yl)methyl]-4-(trifluoromethyl)phenyl]propanoyl]-1,3,4,6-tetrahdropyrrolo[3,4- c]pyrrole-5-carbonyl]benzenesulfonamide;
- or a pharmaceutically acceptable salf thereof.
Dependencies are inferred from the claim text.