US 11,866,427 B2
Kinase inhibitor compounds and compositions and methods of use
Kunal Kumar, New York, NY (US); Peng Wang, New York, NY (US); Roberto Sanchez, New York, NY (US); Adolfo Garcia Ocaña, New York, NY (US); Andrew Stewart, New York, NY (US); and Robert Devita, New York, NY (US)
Assigned to ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, New York, NY (US)
Appl. No. 16/981,742
Filed by Icahn School of Medicine at Mount Sinai, New York, NY (US)
PCT Filed Mar. 20, 2019, PCT No. PCT/US2019/023206
§ 371(c)(1), (2) Date Sep. 17, 2020,
PCT Pub. No. WO2019/183245, PCT Pub. Date Sep. 26, 2019.
Claims priority of provisional application 62/645,560, filed on Mar. 20, 2018.
Prior Publication US 2021/0094950 A1, Apr. 1, 2021
Int. Cl. A61K 31/437 (2006.01); C07D 471/04 (2006.01); A61K 45/06 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/437 (2013.01); A61K 45/06 (2013.01)] 20 Claims
 
1. A compound of formula (I) having the following structure:

OG Complex Work Unit Chemistry
or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof, wherein
R1 is a branched or unbranched C1-6 alkoxy optionally substituted with Y, —NHR5, —C(O)NHCH(CH3)2, or —O(CH2)2OR6, wherein the alkoxy is optionally halogenated or deuterated;
R2 is H or branched or unbranched C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the branched or unbranched C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with Z;
R3 is C1-6 alkyl, halogen, branched or unbranched C1-6 hydroxyalkyl, —C(O)CH3, —OH, or heterocyclyl optionally substituted with R7;
R4 is H, —OH, branched or unbranched C1-6 hydroxyalkyl, or —C(O)CH3;
R5 is H, —C(O)CH3, or —C(O)Ar;
R6 is branched or unbranched C1-6 alkyl, —(CH2)2NHBoc, —(CH2)2NH(O)CH3, or —(CH2)2NH3Cl;
R7 is —ArX or —CH2ArX;
R8 is optional, and when present is O;
X is H or halogen;
Y is —CO2CH3, —NHBoc, —C(O)NH2, —CO2H, —NH3Cl, —NHC(O)CH3; and
Z is —CO2CH3, —CO2H, —C(O)NH2, or an amino-substituted heteroaryl selected from the group consisting of furan, thiophene, pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, and 1,2,3,4-oxatriazole;
with the following provisos:
when R1 is —OCH3, R3 is —CH3, and R4 is H, R2 cannot be —(CH2)2CO2CH3, —(CH2)2CO2H, or —(CH2)2C(O)NH2;
when R1 is —OCH3, R2 is H, and R4 is H, R3 cannot be —CH2OH or Cl; and
when R1 is —OCH3, R2 is H, R3 is —CH3, R4 cannot be H.