US 12,351,581 B2
Compounds for FGFR inhibition
Jay Bradford Fell, Boulder, CO (US); John E. Robinson, Boulder, CO (US); John P. Fischer, Boulder, CO (US); Logan E. Vine, Boulder, CO (US); Martha E. Rodriguez, Boulder, CO (US); Jennifer Fulton, Boulder, CO (US); Tanna Bettendorf, Boulder, CO (US); Bradley J. Newhouse, Boulder, CO (US); Robert A. Rieger, Boulder, CO (US); Cori A. Malinky, Boulder, CO (US); Aaron Christopher Smith, Boulder, CO (US); Ravi Kumar Jalluri, Boulder, CO (US); Mark Joseph Chicarelli, Boulder, CO (US); Leah J. Salituro, Boulder, CO (US); and Macedonio J. Mejia, Boulder, CO (US)
Assigned to Cogent Biosciences, Inc., Waltham, MA (US)
Filed by Cogent Biosciences, Inc., Waltham, MA (US)
Filed on Aug. 19, 2024, as Appl. No. 18/808,641.
Application 18/808,641 is a continuation of application No. PCT/US2024/041350, filed on Aug. 7, 2024.
Claims priority of provisional application 63/614,476, filed on Dec. 22, 2023.
Claims priority of provisional application 63/590,177, filed on Oct. 13, 2023.
Claims priority of provisional application 63/517,996, filed on Aug. 7, 2023.
Prior Publication US 2025/0066352 A1, Feb. 27, 2025
Int. Cl. C07D 471/04 (2006.01); A61K 31/444 (2006.01); A61K 31/4545 (2006.01); A61K 31/496 (2006.01); A61K 31/5377 (2006.01); A61P 35/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/444 (2013.01); A61K 31/4545 (2013.01); A61K 31/496 (2013.01); A61K 31/5377 (2013.01); A61P 35/00 (2018.01)] 30 Claims
 
1. A compound having the following structure of Formula (IV):

OG Complex Work Unit Chemistry
or a stereoisomer of the compound, salt or tautomer of the compound thereof, wherein:
R2 is 5-6 membered heteroaryl optionally substituted with halo;
R3 is selected from the group consisting of H, —OH, halo, C1-C6 alkyl, —C(═O) R4, ═NR5, —NR5R6, —NR5C(═O) R4, oxo, CN, and phosphate, wherein the C1-C6 alkyl is optionally substituted with one or more-OH;
R4 is selected from the group consisting of —C1-C6 alkyl, C1-C6 heteroalkyl, C4-C6 cycloalkyl, and C4-C6 heterocycloalkyl, wherein the C1-C6 alkyl or C4-C6 cycloalkyl is optionally substituted with one or more —OH or —N5SR6;
R5 and R6 are, each independently, H, or C1-C6 alkyl;
X is —(CHCH3)n, —(CHCF3)n—, —(CHCH2OH)n— and —(CHCH2CH3)n—;
n is an integer between 1 and 4;
A is 5-6 membered heteroarylene having at most of two nitrogen atoms, wherein the 5-6 membered heteroarylene is optionally substituted with one or more C1-C6 alkyl, halo, —CN, -NH2, or —(C1-C6 alkylene)-(C1-C6 alkoxy); and
B is C3-C8 cycloalkylene optionally substituted with one or more substituents each independently selected from the group consisting of C1-C6 alkyl, —OH, oxo, C1-C6 alkoxy, halo, C1-C6 haloalkyl, and C1-C6 alkyl alcohol.