US 12,064,426 B2
Selective inhibitors of ROCK1 and ROCK2 protein kinases and uses thereof
Wongil Lee, Bedford, MA (US); William G. Devine, Woburn, MA (US); R. Bruce Diebold, Waltham, MA (US); So Young Hwang, Lexington, MA (US); Yunggeun Choi, Acton, MA (US); Yan Liu, Boston, MA (US); Sang-Ae Seung, Lexington, MA (US); Miyong Yong, Belmont, MA (US); Sewon Kim, Cambridge, MA (US); Jaekyoo Lee, North Andover, MA (US); and Jong Sung Koh, Cambridge, MA (US)
Assigned to GENOSCO Inc., Billerica, MA (US)
Filed by GENOSCO Inc., Billerica, MA (US)
Filed on Jan. 5, 2022, as Appl. No. 17/568,991.
Claims priority of provisional application 63/134,458, filed on Jan. 6, 2021.
Prior Publication US 2023/0082993 A1, Mar. 16, 2023
Int. Cl. A61K 31/4725 (2006.01); A61K 31/4375 (2006.01); A61K 31/496 (2006.01); A61K 31/517 (2006.01); A61K 31/5377 (2006.01); A61K 31/5386 (2006.01); A61K 31/675 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 413/04 (2006.01); C07D 413/14 (2006.01); C07D 471/04 (2006.01); C07D 498/08 (2006.01); C07D 513/04 (2006.01); C07F 9/6558 (2006.01)
CPC A61K 31/4725 (2013.01) [A61K 31/4375 (2013.01); A61K 31/496 (2013.01); A61K 31/517 (2013.01); A61K 31/5377 (2013.01); A61K 31/5386 (2013.01); A61K 31/675 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 413/04 (2013.01); C07D 413/14 (2013.01); C07D 471/04 (2013.01); C07D 498/08 (2013.01); C07D 513/04 (2013.01); C07F 9/65583 (2013.01); C07B 2200/05 (2013.01)] 21 Claims
 
1. A compound of Formula (1), a pharmaceutically acceptable salt, diastereomer, enantiomer, racemate, hydrate, solvate, or prodrug thereof:

OG Complex Work Unit Chemistry
wherein:
X is H or halogen;
Y is N or CR4;
A, B and E each are independently N or CH;
- - - is a single or double bond;
R1 is heteroaryl, C(O)OR5, NHS(O)2R5, S(O)2R5, C(O)NR5R6, or NHC(O)R7, wherein the heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, alkoxy, and a combination thereof;
R2 is H or C1-C3alkyl, which is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, C1-C3alkoxy, NR5R6, and a combination thereof;
R3 is 5-6 membered heteroaryl, wherein one of the carbon atoms within the heteroaryl is connected to the bicyclic ring, wherein the heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, CN, CHF2, CF3, C1-C3alkyl, amino, and a combination thereof, and wherein the 5-6 membered heteroaryl has 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and a combination thereof;
R4 is H, halogen, CF3, CN, C1-C3alkyl, C1-C3alkoxy, or C2-C6alkynyl, wherein the C1-C3alkyl or C2-C6alkynyl is optionally substituted with one or more substituents selected from the group consisting of OH, NH2, C1-C2amino, C1-C2hydroxyl, C1-C2NR5R6, C1-C3alkoxy, and a combination thereof;
R5 is H or C1-C3alkyl, wherein the C1-C3alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, alkoxy, and a combination thereof;
R6 is H, CD3, C1-C6 alkyl, C3-C7cycloalkyl, aryl, heteroaryl, 8-10 membered bicyclic heteroaryl, 8-10 membered saturated or partially unsaturated bicyclic heteroaryl group, or 4-7 membered heterocyclyl comprising 1-2 heteroatoms selected from the group consisting of N, O, S, and a combination thereof, wherein the C1-C6 alkyl, C3-C7cycloalkyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, NR5R6, aryl, heteroaryl, and OR5, and a combination thereof, and wherein when the 4-7 membered heterocyclyl has one nitrogen atom, the 4-7 membered heterocyclyl is optionally substituted with C1-C3 alkyl, CF3, C(O)R5, S(O)2NH2, OCF3, C(O)OR5, or C(O)NHR5 at the nitrogen atom, wherein R6 is independent of each other; and
R7 is C1-C6alkyl, C3-C7cycloalkyl, 4-7 membered heterocyclyl comprising 1-2 heteroatoms selected from the group consisting of N, O, and a combination thereof, 5-6 membered aryl, 5-6 membered heteroaryl, 8-10 membered bicyclic heteroaryl, 8-10 membered saturated or partially unsaturated bicyclic heteroaryl group, wherein the C1-C6alkyl or C3-C7 cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C3alkyl, OR5, NH2, 5-6 membered heteroaryl, and a combination thereof.