Back to results
US 11,897,880 B2Granted
7,8-dihydrobenzo[e]pyrido[3,4-c]azocine-2,5(3H,6H)-dione derivatives useful as a factor XIa inhibitors
AssigneeJanssen Pharmaceutica NV
InventorsGuozhang Xu, Tianbao Lu, Zhijie Liu, Micheal D. Gaul
Life of this patent
Estimating the term…
Abstract
The present invention is directed to 7,8-dihydrobenzo[e]pyrido[3,4-c]azocine-2,5(3H,6H)-dione derivatives, stereoisomers, isotopologues, isotopomers and pharmaceutically acceptable salts thereof, pharmaceutical compositions containing said compounds and the use of said compounds in the treatment and/or prophylaxis of thromboembolic disorders, inflammatory disorders and diseases or conditions in which plasma kallikrein activity is implicated.
Claims11
A compound of formula (I)
- wherein
- R1 is selected from the group consisting of hydrogen, C1-2alkyl, —(C1-2alkylene)-OH and —(C1-2alkylene)-O-(C1-2alkyl);
- R2 is hydrogen and R3 is cyclopropyl-methyl-;
- alternatively, R2 and R3 are taken together with the carbon atoms to which they are bound to form
- R4 is selected from the group consisting of hydrogen and halogen;
- R5 is selected from the group consisting of phenyl, heteroaryl and pyridin-4-yl-1-oxide;
- wherein the phenyl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, C1-4alkyl, hydroxy substituted C1-4alkyl, NRARB and —NH—C(O)-(C1-4alkyl);
- wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-2alkyl;
- a is an integer from 0 to 3;
- each R6 is independently selected from the group consisting of chloro, fluoro and methyl;
- R7 is hydrogen, and R8 and R9 are each independently selected from the group consisting of hydrogen, C1-4alkyl, and C1-4alkoxy;
- alternatively, R7 is hydrogen, and R8 and R9 are taken together with the carbon atom to which they are bound to form a ring structure selected from the group consisting of cycloprop-1,1-diyl, cyclobut-1,1-diyl, cyclopent-1,1-diyl, and cyclohex-1,1-yl;
- alternatively, R9 is hydrogen, and R7 and R8 are taken together with the carbon atoms to which they are bound to form a ring structure selected from the group consisting of phen-1,2-diyl and pyridin-3,4-diyl;
- or a stereoisomer, isotopologue, isotopomer, or pharmaceutically acceptable salt or solvate thereof.
11 more elements
A compound of formula (I)
- wherein
- R1 is selected from the group consisting of hydrogen, methyl, 2-hydroxy-ethyl- and 2-methoxy-ethyl-;
- R2 is hydrogen and R3 is cyclopropyl-methyl-;
- alternatively, R2 and R3 are taken together with the carbon atoms to which they are bound to form;
- R4 is selected from the group consisting of hydrogen and fluoro;
- R5 is selected from the group consisting of 4-fluoro-phenyl, 4-(methoxy-carbonyl-amino)-phenyl, 1-methyl-imidazol-5-yl, 1-methyl-1,2,3-triazol-5-yl, 1-methyl-pyrimidin-4-yl-6-one, 2-fluoro-6-amino-pyridin-3-yl, 2-chloro-6-amino-pyridin-3-yl, 1-methyl-pyridin-3-yl-6-one, pyridin-4-yl, 2-chloro-6-amino-pyridin-4-yl, 2-(hydroxy-methyl)-3-fluoro-pyridin-4-yl, 2-fluoro-6-amino-pyridin-4-yl, 1-methyl-pyridin-4-yl-6-one, pyridin-4-yl-1-oxide, 2-chloro-6-amino-pyridin-5-yl, indol-5-yl, indazol-5-yl, benzimidazol-5-yl, benzothiazol-5-yl, 2-methyl-benzothiazol-5-yl, benzo[1,2,3]thiadiazol-5-yl, imidazo[1,2-a]pyridin-7-yl, 3-bromo-imidazo[1,2-a]pyridin-7-yl and [1,2,4]triazolo[4,3-a]pyridin-7-yl;
- a is an integer from 1 to 2;
- each R6 is independently selected from the group consisting of 11-chloro and 12-fluoro;
- R7 is hydrogen, and R8 and R9 are the same and selected from the group consisting of hydrogen, and methyl;
- alternatively, R7 is hydrogen, and R8 and R9 are taken together with the carbon atom to which they are bound to form a ring structure selected from the group consisting of cycloprop-1,1-diyl, cyclobut-1,1-diyl and cyclopent-1,1-diyl;
- alternatively, R9 is hydrogen, and R7 and R8 are taken together with the carbon atoms to which they are bound to form a ring structure selected from the group consisting of phen-1,2-diyl and pyridin-3,4-diyl;
- or stereoisomer or pharmaceutically acceptable salt thereof.
9 more elements
Dependencies are inferred from the claim text.