US 11,897,880 B2
7,8-dihydrobenzo[e]pyrido[3,4-c]azocine-2,5(3H,6H)-dione derivatives useful as a factor XIa inhibitors
Guozhang Xu, Chesterbrook, PA (US); Tianbao Lu, Churchville, PA (US); Zhijie Liu, Wilmington, DE (US); and Micheal D. Gaul, Apex, NC (US)
Assigned to Janssen Pharmaceutica NV, Beerse (BE)
Filed by Janssen Pharmaceutica NV, Beerse (BE)
Filed on Apr. 29, 2022, as Appl. No. 17/732,724.
Claims priority of provisional application 63/182,019, filed on Apr. 30, 2021.
Prior Publication US 2022/0389005 A1, Dec. 8, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 11 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
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

OG Complex Work Unit Chemistry
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.