US 12,440,494 B2
Compounds useful for inhibiting RAF dimers
Evripidis Gavathiotis, Roslyn, NY (US); and Bogos Agianian, Bayside, NY (US)
Assigned to ALBERT EINSTEIN COLLEGE OF MEDICINE, Bronx, NY (US)
Appl. No. 17/432,589
Filed by ALBERT EINSTEIN COLLEGE OF MEDICINE, Bronx, NY (US)
PCT Filed Feb. 25, 2020, PCT No. PCT/US2020/019695
§ 371(c)(1), (2) Date Aug. 20, 2021,
PCT Pub. No. WO2020/176501, PCT Pub. Date Sep. 3, 2020.
Claims priority of provisional application 62/810,799, filed on Feb. 26, 2019.
Claims priority of provisional application 62/810,056, filed on Feb. 25, 2019.
Prior Publication US 2022/0265669 A1, Aug. 25, 2022
Int. Cl. A61K 31/5377 (2006.01); A61K 31/495 (2006.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); A61P 35/00 (2006.01); C07D 295/13 (2006.01); C07D 487/04 (2006.01)
CPC A61K 31/5377 (2013.01) [A61K 31/495 (2013.01); A61K 31/5025 (2013.01); A61K 31/506 (2013.01); A61P 35/00 (2018.01); C07D 295/13 (2013.01); C07D 487/04 (2013.01)] 12 Claims
 
1. A compound having the structure

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or any of the foregoing, where
Ring C is a 5-6-membered heterocycloalkyl, partially unsaturated, or heteroaryl group containing at least one Nitrogen ring atom and containing 0-3 additional ring heteroatoms independently chosen from N, O, and S, that is optionally substituted by one or more substituents independently chosen from RC;

OG Complex Work Unit Chemistry
L2 is a C1-C4alkylene linker in which one single bond is optionally replaced by a triple bond;
L3 is a bond or a C1-C4alkylene linker, which is optionally substituted with an oxo group;
RA, RB, and RD are independently chosen at each occurrence from halogen, hydroxyl, cyano, nitro, amino, oxo, and Y;
RC is independently chosen at each occurrence from halogen, hydroxyl, cyano, nitro, amino, oxo, —SO2F, —SO2NH2, Y, and Z;
Y is a C1-C8 alkyl group, optionally chosen at each occurrence, in which any single bond is optionally replaced by a double or triple bond and one or more CH2 groups in the C1-C8alkyl is optionally replaced by —O—, —S—, —S(═O)—, —S(═O)2—, —P(═O)—, or N(R2)—, and which is optionally substituted by one or more substituents independently chosen from halogen, hydroxyl, amino, cyano, oxo (═O), thiol (—SH), thione (═S), ═NR1, and C3-C6cycloalkyl;
Z is C3-C6cycloalkyl, C3-C6cycloalkenyl(C0-C2alkyl)-, aryl(C0-C2alkyl)-, (5- to 7-membered heterocycloalkyl)(C0-C2alkyl)-, (5- to 6-membered partially unsaturated heterocycloalkyl)(C0-C2alkyl), or (5- to 6 membered heteroaryl)(C0-C2alkyl)-, which Z is optionally substituted by one or more substituents independently chosen from halogen, hydroxyl, cyano, nitro, oxo, amino, —SO2F, —SO2CH3, and C1-C6 alkyl, in which any single bond is optionally replaced by a double or triple bond, and each —CH2 group is optionally replaced by a S, N, or O heteroatom and which is optionally substituted by one or more independently chosen halogen, hydroxyl, amino, cyano, oxo, and amino substituents; and
R2 is independently chosen and each occurrence from hydrogen, C1-C6alkyl, and (C3-C6cycloalkyl)C0-C4alkyl.