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US 2026/0297066 A1Published application
Compounds for treating cancer
AssigneeGenesis Molecular AI, Inc.
InventorsBrett Busch, Brandon Reinus, William F. Vernier, Martin Indarte
Life of this patent
Estimating the term…
Abstract
This disclosure provides compounds of Formula (I) and pharmaceutically acceptable salts thereof, that inhibit phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα).
Claims25
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is hydrogen, cyano, C3-C6 cycloalkyl, C1-C6 alkyl optionally substituted with phenyl optionally substituted with halogen, C1-C6 thioalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 alkoxyalkyl;
- R1′ is hydrogen or C1-C6 alkyl;
- or R1 and R1′, together with the carbon atom to which they are attached form a C3-C10 cycloalkyl;
- R2 is C6-C12 aryl optionally substituted with 1-4 independently selected R2A, 5-10 membered heteroaryl optionally substituted with 1-4 independently selected R2A, 4-10 membered heterocyclyl optionally substituted with 1-4 independently selected R2A, C4-C10 cycloalkyl optionally substituted with 1-4 independently selected R2A, C1-C6 alkoxyalkyl optionally substituted with —C(═O)NRARC, C1-C6 aralkyl optionally substituted with 1-4 independently selected R2A, or C1-C6 alkoxy optionally substituted with —C(═O)NRARC;
- each R2A is independently selected from:
- (i) halogen,
- (ii) cyano,
- (iii) hydroxyl,
- (iv) —NRARB,
- (v) —C(═O)NRARB,
- (vii) —NHC(═O)RC,
- (viii) —C(═O)RD,
- (ix) —C(═O)ORE,
- (x) —SO2RF,
- (xi) —NHSO2RF,
- (xii) —SO2NRFRG,
- (xiii) —NHC(═O)C1-C6 alkyl optionally substituted with NRARB,
- (xiv) C1-C6 haloalkyl,
- (xv) C1-C6 hydroxyalkyl,
- (xvi) 5-10 membered heteroaryl optionally substituted with 1-3 substituents independently selected from C1-C6 alkyl, —C(═O)NRARB, C1-C6 haloalkyl, and —NRARB,
- (xvii) 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 haloalkyl, —C(═O)C1-C6 alkyl, —SO2(C1-C6 alkyl), —SO2NRFRG, C6-C12 aryl, C1-C6 alkyl optionally substituted with C1-C6 alkoxy, —C(═O)NRARB, or —NHC(═O)C1-C6 alkyl optionally substituted with —NRARB,
- (xviii) C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, oxo, —NRARB, —C(═O)NRARB, C1-C6 alkoxy, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl optionally substituted with hydroxyl, C1-C6 alkyl, aralkyl, heteroaralkyl, —C(═O)NRARB, or —C(═O)C3-C6 cycloalkyl,
- (xix) C1-C6 alkoxy optionally substituted with —NRARB or 4-10 membered heterocyclyl optionally substituted with C1-C6 alkyl, hydroxyl, aralkyl, heteroaralkyl, or —C(═O)C3-C6 cycloalkyl,
- (xx) C3-C6 cycloalkyl optionally substituted with 4-10 membered heterocyclyl optionally substituted with C1-C6 alkyl;
- (xxi) C6-C12 aryl optionally substituted with 1-3 substituents independently selected from hydroxyl, cyano, C1-C6 haloalkyl, —ORE, —C(═O)C1-C6 alkyl, —SO2(C1-C6 alkyl), —SO2NRFRG, 4-10 membered heterocyclyl, or C1-C6 alkyl optionally substituted with C1-C6 alkoxy, hydroxyl, or —C(═O)NRARB;
- and
- (xxii) 4-10 membered heterocyclyloxy optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 haloalkyl, —C(═O)C1-C6 alkyl, —SO2(C1-C6 alkyl), —SO2NRFRG, C6-C12 aryl, C1-C6 alkyl optionally substituted with C1-C6 alkoxy, —C(═O)NRARB, or —NHC(═O)C1-C6 alkyl optionally substituted with —NRARB;
- each RA and RB is independently selected from hydrogen, hydroxyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl, cyano, 4-10 membered heterocyclyl, and C1-C6 alkyl optionally substituted with hydroxyl or C1-C6 alkoxy, or RA and RB together with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-2 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, and —C(═O)C1-C6 alkyl;
- each RC is independently selected from C3-C6 cycloalkyl, —C(═O)NHRY1, C2-C6 alkenyl, or a C1-C6 alkyl optionally substituted with —NRARB or with 4-10 membered heterocyclyl optionally substituted with C1-C6 alkyl or with C1-C6 hydroxylalkyl;
- each RD and RE is independently selected from hydrogen, hydroxyl, C1-C6 alkyl, phenyl, 4-10 membered heterocyclyl, —NRARB, C1-C6 alkoxy, and C3-C6 cycloalkyl, wherein the C1-C6 alkyl, 4-10 membered heterocyclyl, and phenyl are optionally substituted with 4-10 membered heterocyclyl, C3-C6 cycloalkyl, or cyano, and the C3-C6 cycloalkyl is optionally substituted with C1-C6 alkyl optionally substituted with hydroxyl or C1-C6 alkoxy;
- each R3A and R3B is independently selected from hydrogen C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 haloalkyl, or R3A and R3B, together with the carbon and nitrogen atoms, respectively, to which they are attached together form a 4-8 membered heterocyclyl group;
- R4 is hydrogen, C1-C6 alkyl, or acrylamido;
- R5 is hydrogen, C1-C6 alkyl, halogen, C1-C6 haloalkyl, C3-C6 cycloalkyl, cyano, —NR5AR5B, —NR5AC(═O)R5B, or —C(═O)NR5AR5B;
- R5A and R5B are independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, and C1-C6 hydroxyalkyl;
- R6 is hydrogen, halogen, or C1-C6 alkyl;
- X is a bond, CH2, CH(CH3), C(CH3)2, or
- Y is phenyl optionally substituted with 1-3 independently selected RY, naphthyl optionally substituted with 1-3 independently selected RY, or 5-10 membered heteroaryl optionally substituted with 1-3 independently selected RY;
- each RY is independently selected from:
- halogen, cyano, hydroxyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, —NHC(═O)RC, —C(═O)NHR, —CO2RA, —SO2NRFRG, —NHSO2RF, —S(═O)(═NRF)RG, —SO2(C1-C6 alkyl), —C(═O)NRARB, 5-6 membered heteroaryl, heteroaralkyl, and C1-C6 alkyl optionally substituted with —CO2RA or 5-6 membered heteroaryl optionally substituted with RY1;
- RY1 is —SO2(C1-C6 alkyl), hydroxyl, or C1-C6 alkyl optionally substituted with oxo;
- and
- each RF and RG is independently selected from hydrogen, phenyl, and C1-C6 alkyl optionally substituted with oxo or —NRARB.
40 more elements
A compound selected from the group consisting of the compounds in Table A, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.