US2020223854A1PendingUtilityA1
Bicyclic compounds as dual atx/ca inhibitors
Est. expirySep 24, 2035(~9.2 yrs left)· nominal 20-yr term from priority
Inventors:Patrick Di GiorgioJerome HertDaniel HunzikerPatrizio MatteiMarkus RudolphPetra SchmitzChristoph Ullmer
A61K 31/407A61P 27/02C07D 487/04A61K 31/437C07D 471/04A61K 31/5517
59
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Claims
Abstract
wherein R1, R2, Y, W, m, n, p and q are as defined herein, compositions including the compounds and methods of using the compounds.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . Compounds 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 quinolinyl, substituted quinolinyl-C 1-6 -alkyl, substituted quinolinyl-C 1-6 -lalkenyl, substituted quinolinyl-C 1-6 -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 quinolinyl, substituted quinolinyl-C 1-6 -alkyl, substituted quinolinyl-C 1-6 -lalkenyl, substituted quinolinyl-C 1-6 -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 a —OC(O)— or —C(O)—;
W is —C(O)—, —S(O) 2 — or —CR 6 R 7 —;
R 2 is substituted phenyl, substituted pyridinyl or substituted thiophenyl, wherein substituted phenyl, substituted pyridinyl and substituted thiophenyl are substituted by R 6 , R 7 and R 8 ;
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 3-8 -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 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy, C 3-8 -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 aminosulfonyl;
R 7 and R 8 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 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy and C 3-8 -cycloalkoxy-C 1-6 -alkyl;
m, n, p and q are independently selected from 1 or 2;
and pharmaceutically acceptable salts.
2 . A compound according to claim 1 , wherein
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 a —OC(O)— or —C(O)—;
W is —C(O)—, —S(O) 2 — or —CR 6 R 7 —;
R 2 is substituted phenyl, substituted pyridinyl or substituted thiophenyl, wherein substituted phenyl, substituted pyridinyl and substituted thiophenyl are substituted by R 6 , R 7 and R 8 ;
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 3-8 -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 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy, C 3-8 -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 aminosulfonyl;
R 7 and R 8 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 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, C 3-8 -cycloalkyl-C 1-6 -alkoxy, C 3-8 -cycloalkoxy and C 3-8 -cycloalkoxy-C 1-6 -alkyl;
m, n, p and q are independently selected from 1 or 2;
and pharmaceutically acceptable salts.
3 . A compound according to claim 1 , wherein
R 1 is substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted quinolinyl-C 1-6 -alkyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted quinolinyl-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 a —OC(O)— or —C(O)—; W is —C(O)—; R 2 is substituted phenyl or substituted pyridinyl, wherein substituted phenyl and substituted pyridinyl are substituted by R 6 , R 7 and R 8 ; R 3 is halo-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl, C 1-6 -alkylpiperidinyl-C 1-6 -alkoxy or tetrahydropyranyl-C 1-6 -alkoxy; R 4 is H, cyano, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl; R 5 is H; R 6 is aminosulfonyl; R 7 and R 8 are independently selected from H or halogen; m and q are 1; n and p are independently selected from 1 or 2; and pharmaceutically acceptable salts.
4 . A compound according to anyone of claims 1 to 3 , wherein
R 1 is substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4 and R 5 ;
Y is a —OC(O)— or —C(O)—;
W is —C(O)—;
R 2 is substituted phenyl or substituted pyridinyl, wherein substituted phenyl and substituted pyridinyl are substituted by R 6 , R and R 8 ;
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, cyano, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl;
R 5 is H;
R 6 is aminosulfonyl;
R 7 and R 8 are independently selected from H or halogen;
m and q are 1;
n and p are independently selected from 1 or 2;
and pharmaceutically acceptable salts.
5 . A compound according to anyone of claim 1 to 4 , wherein R 1 is substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted quinolinyl-C 1-6 -alkyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted quinolinyl-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 anyone of claim 1 to 5 , wherein R 1 is substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4 and R 5 .
7 . A compound according to any one of claims 1 to 6 , wherein R 1 is pyridinyl-C 1-6 -alkyl substituted by R 3 , R 4 and R 5 .
8 . A compound according to any one of claims 1 to 7 , wherein Y is —OC(O)—.
9 . A compound according to any one of claims 1 to 8 , wherein R 2 is substituted phenyl or substituted pyridinyl, wherein substituted phenyl and substituted pyridinyl are substituted by R 6 , R 7 and R 8 .
10 . A compound according to any one of claims 1 to 9 , wherein R 2 is phenyl substituted by R 6 , R 7 and R 8 .
11 . A compound according to any one of claims 1 to 10 , wherein R 3 is halo-C 1-6 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl, C 1-6 -alkylpiperidinyl-C 1-6 -alkoxy or tetrahydropyranyl-C 1-6 -alkoxy.
12 . A compound according to any one of claims 1 to 11 , wherein R 3 is halo-C 16 -alkoxy, C 1-6 -alkylcarbonylamino, C 1-6 -alkyltetrazolyl-C 1-6 -alkyl or tetrahydropyranyl-C 1-6 -alkoxy.
13 . A compound according to any one of claims 1 to 12 , wherein R 3 is C 1-6 -alkylcarbonylamino.
14 . A compound according to any one of claims 1 to 13 , wherein R 4 is H, cyano, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl.
15 . A compound according to any one of claims 1 to 14 , wherein R 4 is halo-C 16 -alkyl.
16 . A compound according to any one of claims 1 to 15 , wherein R 5 is H.
17 . A compound according to any one of claims 1 to 16 , wherein R 7 and R 8 are independently selected from H or halogen.
18 . A compound according to any one of claims 1 to 17 , wherein R 7 is halogen.
19 . A compound according to any one of claims 1 to 18 , wherein R 8 is H.
20 . A compound according to any one of claims 1 to 19 , wherein m and q are 1 and n and p are independently selected from 1 or 2.
21 . A compound according to any one of claims 1 to 20 , wherein m, n, p and q are 1.
22 . A compound according to any one of claims 1 to 21 , wherein
R 1 is 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 phenyl substituted by R 6 , R 7 and R 8 ;
R 3 is C 1-6 -alkylcarbonylamino;
R 4 is halo-C 1-6 -alkyl;
R 5 is H;
R 7 is halogen;
R 8 is H;
m, n, p and q are 1
and pharmaceutically acceptable salts.
23 . A compound according to claim 1 and of formula I(a),
wherein
R 1 is substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl or substituted pyridinyl-C 1-6 -alkyl, wherein substituted phenyl-C 1-6 -alkyl, substituted phenoxy-C 1-6 -alkyl, substituted phenyl-C 2-6 -alkenyl, substituted pyridinyl and substituted pyridinyl-C 1-6 -alkyl are substituted by R 3 , R 4 and R 5 ;
Y is a —OC(O)— or —C(O)—;
W is —C(O)—;
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, cyano, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl or C 3-8 -cycloalkyl;
R 5 is H;
R 7 and R 8 are independently selected from H or halogen;
m and q are 1;
n and p are independently selected from 1 or 2;
and pharmaceutically acceptable salts.
24 . A compound according to claim 1 and of formula I(b),
wherein
R 1 is pyridinyl-C 1-6 -alkyl substituted by R 3 , R 4 and R 5 ;
Y is —OC(O)—;
W is —C(O)—;
R 3 is C 1-6 -alkylcarbonylamino;
R 4 is halo-C 1-6 -alkyl;
R 5 is H;
R 7 is halogen;
R 8 is H;
m, n, p and q are 1
and pharmaceutically acceptable salts.
25 . A compound according to any one of claims 1 to 24 , selected from
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(2,5-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-chloro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[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;
[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;
4-(trifluoromethoxy)benzyl 5-(4-sulfamoylbenzoyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;
6-[5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carbonyl]pyridine-3-sulfonamide;
4-[5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carbonyl]-3-fluorobenzenesulfonamide;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
3-fluoro-4-(5-(3-(2-((5-methyl-2H-tetrazol-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoyl)-1,2,3,4,5,6-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzenesulfonamide;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(2,6-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,6-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,5-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-6-methylpyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[6-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[6-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,5-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[6-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[6-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[6-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,6-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-cyano-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-cyano-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,6-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-cyano-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5-cyano-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,5-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 6-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,5,7,8-hexahydro-2,6-naphthyridine-2-carboxylate;
[5-chloro-4-cyano-2-(2,2-dimethylpropanoylamino)phenyl]methyl 2-(5-sulfamoylpyridine-2-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[4-(trifluoromethoxy)phenyl]methyl 6-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,5,7,8-hexahydro-2,6-naphthyridine-2-carboxylate;
[4-(trifluoromethoxy)phenyl]methyl 2-(5-sulfamoylpyridine-2-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[4-(trifluoromethoxy)phenyl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
3-fluoro-4-[2-[(E)-3-[4-(trifluoromethoxy)phenyl]prop-2-enoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
6-[2-[3-[4-(trifluoromethoxy)phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]pyridine-3-sulfonamide;
3-fluoro-4-[2-[3-[4-(trifluoromethoxy)phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
6-[2-[(E)-3-[4-(trifluoromethoxy)phenyl]prop-2-enoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]pyridine-3-sulfonamide;
6-[2-[2-[4-(trifluoromethoxy)phenoxy]acetyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]pyridine-3-sulfonamide;
3-fluoro-4-[2-[2-[4-(trifluoromethoxy)phenoxy]acetyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
4-[2-[3-[4-cyano-2-[(5-methyltetrazol-2-yl)methyl]phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-3-fluorobenzenesulfonamide;
4-[2-[3-[4-chloro-2-[(5-methyltetrazol-2-yl)methyl]phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-3-fluorobenzenesulfonamide;
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;
3-fluoro-4-[2-[3-[2-[(4-methyltriazol-1-yl)methyl]-4-(trifluoromethyl)phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
and pharmaceutically acceptable salts thereof.
26 . A compound according to any one of claims 1 to 25 , selected from
[5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[5,6-dichloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,6-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-fluoro-5-sulfamoylpyridine-2-carbonyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
4-[5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carbonyl]-2,3-difluorobenzenesulfonamide;
4-[5-[2-cyclopropyl-6-[(1-methylpiperidin-4-yl)methoxy]pyridine-4-carbonyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carbonyl]-2,3-difluorobenzenesulfonamide;
[5-chloro-3-[(5-methyltetrazol-2-yl)methyl]pyridin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
3-fluoro-4-[2-[3-[3-[(5-methyltetrazol-2-yl)methyl]-5-(trifluoromethyl)pyridin-2-yl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]benzenesulfonamide;
5-fluoro-6-[2-[3-[2-[(5-methyltetrazol-2-yl)methyl]-4-(trifluoromethyl)phenyl]propanoyl]-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carbonyl]pyridine-3-sulfonamide;
[3-(2,2-dimethylpropanoylamino)quinolin-2-yl]methyl 2-(2-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 5-(2-fluoro-4-sulfamoylphenyl)sulfonyl-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-2-carboxylate;
and pharmaceutically acceptable salts thereof.
27 . A compound according to any one of claims 1 to 26 , selected from
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-chloro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[3-(2,2-dimethylpropanoylamino)-5-(trifluoromethyl)pyridin-2-yl]methyl 2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
[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;
[5-chloro-3-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl 2-(2,3-difluoro-4-sulfamoylbenzoyl)-1,3,4,6-tetrahydropyrrolo[3,4-c]pyrrole-5-carboxylate;
and pharmaceutically acceptable salts thereof.
28 . A process to prepare a compound according to any one of claims 1 to 27 comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III), wherein R 1 , R 2 , m, n, p and q are as defined in any one of claim 1 to 24 and W is —C(O)—.
29 . A compound according to any one of claims 1 to 27 for use as therapeutically active substance.
30 . A pharmaceutical composition comprising a compound according to any one of claims 1 to 27 and a therapeutically inert carrier.
31 . The use of a compound according to any one of claims 1 to 27 for the treatment or prophylaxis of ocular conditions.
32 . A compound according to any one of claims 1 to 27 for the treatment or prophylaxis of ocular conditions.
33 . The use of a compound according to any one of claims 1 to 27 for the preparation of a medicament for the treatment or prophylaxis of ocular conditions.
34 . A method for the treatment or prophylaxis ocular conditions, which method comprises administering an effective amount of a compound according to any one of claims 1 to 27 .
35 . A compound according to any one of claims 1 to 27 , when manufactured according to a process of claim 28 .
36 . The invention as hereinbefore described.Join the waitlist — get patent alerts
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