US 12,479,857 B2
Bax inhibitors and uses thereof
Shigemi Matsuyama, Cleveland, OH (US); and William Greenlee, Cleveland, OH (US)
Assigned to CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
Appl. No. 17/615,377
Filed by CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
PCT Filed Jun. 1, 2020, PCT No. PCT/US2020/035564
§ 371(c)(1), (2) Date Nov. 30, 2021,
PCT Pub. No. WO2021/002986, PCT Pub. Date Jan. 7, 2021.
Claims priority of provisional application 62/855,185, filed on May 31, 2019.
Prior Publication US 2022/0389028 A1, Dec. 8, 2022
Int. Cl. C07D 495/04 (2006.01); C07C 13/28 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 413/12 (2006.01); C07D 491/048 (2006.01); C07D 519/00 (2006.01)
CPC C07D 495/04 (2013.01) [C07C 13/28 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 413/12 (2013.01); C07D 491/048 (2013.01); C07D 519/00 (2013.01)] 8 Claims
 
1. A compound including the following formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
R1 and R2 are each independently —H, alkyl, —F, —CN, —O-alkyl, cycloalkyl, oxetanyl, or tetrahydrofuranyl, or R1 together with R2 forms a phenyl ring optionally substituted with one or two R8 groups, or R1 together with R2 forms a five or six-membered heteroaromatic ring containing one or two heteroatoms chosen from N, O and S, optionally substituted with one or two R8 groups;
R8 is halo, alkyl, cycloalkyl, oxetanyl, tetrahydrofuranyl, —CN, —O-alkyl, —O-cycloalkyl, —SO2-alkyl, or —CH2SO2-alkyl;
R3 is absent, —H, —D, —F, —Cl, —CF3, -alkyl, cyclopropyl-O-alkyl, or —CN;
R4 is —H, alkyl, cyclopropyl, or —CF3;
R5 is absent, —H, or alkyl;
alternatively, R5 and the nitrogen atom to which it is attached may be replaced by an oxygen atom;
V and W are each independently C or N;
X, Y and Z are each independently —CH, or N;
X1 and Z1 are each independently —CH or N;
W1 and Y1 are each independently C or N, and when Y1 is N, R3 is absent;
X2 is O or N, when X2 is O, R5 is absent;
custom character represents a single or double bond;
R6 is selected from the group consisting of:

OG Complex Work Unit Chemistry
R7 is —H, halo, alkyl, cycloalkyl, —CN, —O-alkyl, —O-cycloalkyl, —O-heterocyclyl, —SO2-alkyl, —CH2SO2-alkyl, —CONH2, —CONH-alkyl, or —CON(alkyl)2;
alternatively, R7 can be an aryl optionally substituted with one or two R9 groups;
alternatively, R7 can be a 4-6 membered ring heterocycle containing one or two heteroatoms chosen from the group consisting of N, O and S, and optionally substituted with one or two R9 groups, excluding unstable heterocycles;
alternatively, R7 can be a 5-6 membered ring heteroaryl group containing one to four heteroatoms chosen from the group consisting of N, O and S, and optionally substituted with one or two R9 groups, excluding unstable heterocycles;
R9 is H, halo, alkyl, cycloalkyl, alkyl-CO—, oxetanyl, 3-tetrahydrofuranyl, —CN, —O-alkyl, —O-cycloalkyl, —CONH2, —CONH-alkyl, or —CON (alkyl)2; or
alternatively, R6 together with R7 and the phenyl ring or heteroaryl ring to which they are attached, may be benzotriazole ring, azaindole ring, or azaindazole, with N of the rings bearing an optional substituent R10, and with Cs of the rings optionally substituted with R11;
R10 is —H, alkyl, or cycloalkyl; and
R11 is —H, alkyl, or cycloalkyl.