Heterocyclic compounds and uses thereof
AssigneeKayoThera Inc.
InventorsMark ESPOSITO, John PROUDFOOT, John PIWINSKI
Life of this patent
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Abstract
Provided herein are compounds of Formula (I), or pharmaceutically acceptable salt thereof, wherein R100, p, ring A, L, R22′, R22, R32, and R33 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt thereof, e.g., in the treatment of a disease or disorder that is treatable by administration of an aldehyde dehydrogenase (e.g., ALDH1a3 and/or ALDH1a2) inhibitor.
Claims60
A compound of Formula (III)
- or a pharmaceutically acceptable salt or deuterated form thereof,
- wherein:
- ring A is heteroaryl, heterocyclyl, or aryl;
- L is —C(O)—NH—, —C(NRA)—NH—, —C(O)—N(RA)-alkylene-O—, or -(alkylene)-N(RA)-alkylene-O—;
- R22 is halo, —CN, —C1-6 alkyl, —C1-6 alkyl-CN, —C1-6 haloalkyl, -carbocyclyl, or —C1-6 alkyl-carbocyclyl;
- R22′ is H, —CN, halo, —C1-6alkyl, —C1-6haloalkyl, —C1-6 alkyl-CN, carbocyclyl, or —C1-6 alkyl-carbocyclyl;
- p is 0, 1, or 2;
- each R100 is independently halo, —CN, hydroxy, —C1-6 alkyl, —C1-6 alkylene-carbocyclyl, —C1-6alkylene-heterocyclyl, —C1-6haloalkyl, carbocyclyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with 1 or 2 R101;
- each R101 is independently halo, —CN, hydroxy, or —C1-6 alkyl;
- and
- RA is H or —C1-6 alkyl
- wherein the compound is not
A compound of Formula (IV):
- or a pharmaceutically acceptable salt or deuterated form thereof,
- wherein:
- R1 is H and R2 is H, or R1 and R2 are joined to form a carbocyclyl;
- R22 is halo, —CN, —C1-6alkyl, —C1-6 alkyl-CN, —C1-6haloalkyl, carbocyclyl, or —C1-6 alkyl-carbocyclyl;
- R22′ is H, —CN, halo, —C1-6 alkyl, —C1-6 haloalkyl, —C1-6alkyl-CN, carbocyclyl, or —C1-6 alkyl-carbocyclyl;
- p is 0, 1, or 2;
- each R100 is independently halo, —CN, hydroxy, —C1-6 alkylene-carbocyclyl, —C1-6 alkyl, —C1-6 haloalkyl, or carbocyclyl;
- Z1, Z2, and Z3 are independently selected from —CH—, —S—, —N—, —NH—, and —O—;
- and
- the dashed line represents a double or is absent to provide an aromatic ring;
- wherein the compound is not
A compound of Formula (V):
- or a pharmaceutically acceptable salt or deuterated form thereof,
- wherein:
- R1 is H and R2 is H, or R1 and R2 are joined to form a carbocyclyl;
- R22 is halo, —CN, —C1-6 alkyl, —C1-6 alkyl-CN, —C1-6 haloalkyl, carbocyclyl, or —C1-6 alkyl-carbocyclyl;
- q is 0, 1, or 2;
- each R101 is independently halo, —CN, hydroxy, —C1-6alkyl, or —C1-6 haloalkyl;
- and
- X2 is —CH— or —N—.
The compound of any one of the preceding claims, wherein R101 is fluoro, hydroxy, —CN, or methyl.
A compound selected from:
Dependencies are inferred from the claim text.