Lysine acetyltransferase 6a (kat6a) inhibitor, combinations and uses thereof

A method of treating cancer in a subject in need thereof, the method comprising administering to the subject:

• (a) a compound of Formula (I), or a pharmaceutically acceptable salt thereof:
• wherein:
• Y1 is CR1a or N;
• Y2 is CR2a or N;
• Y3 is CR3a or N;
• Y4 is CR4a or N;
• Y5 is CR5a or N;
• Z1 is CR1b or N;
• Z2 is CR2b or N;
• Z3 is CR3b or N;
• wherein at least one of Y1, Y2, Y3, Y4, Y5, Z1, Z2, and Z3 is N;
• X is selected from —C(R6)(R6a)—, —O—, and —N(R7)—;
• R1 is C1-9heteroaryl optionally substituted with one, two, or three groups selected from R15a;
• R1a, R2a, R3a, R4a, R5a, R1b, R2b, and R3b are independently selected from hydrogen, halogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR10, —SR10, —SF5, —N(R10)(R11), —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)OR13, —N(R12)S(O)2R13, —C(O)R13, —S(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —N(R12)C(O)R13, —S(O)2R13, —S(O)2N(R10)(R11)—, S(═O)(═NH)N(R10)(R11), —CH2C(O)N(R10)(R11), —CH2N(R12)C(O)R13, —CH2S(O)2R13, and —CH2S(O)2N(R10)(R11), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from R15b;
• R6 and R6a are independently selected from hydrogen, halogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR10, —SR10, —N(R10)(R11), —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)OR13, —N(R12)S(O)2R13, —C(O)R13, —S(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —N(R12)C(O)R13, —S(O)2R13, —S(O)2N(R10)(R11)—, S(═O)(═NH)N(R10)(R11), —CH2C(O)N(R10)(R11), —CH2N(R12)C(O)R13, —CH2S(O)2R13, and -CH2S(O)2N(R10)(R11), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• R7 is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R10 is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R11 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R12 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R13 is independently selected C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• and
• each R15a and each R15b are each independently selected from halogen, oxo, —CN, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, —CH2—C3-6cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, C1-9heteroaryl, —CH2—C1-9heteroaryl, —OR10, —SR10, —N(R10)(R11), —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)OR13, —N(R12)S(O)2R13, —C(O)R13, —S(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —N(R12)C(O)R13, —S(O)2R13, —S(O)2N(R10)(R11)—, S(═O)(═NH)N(R10)(R11), —CH2C(O)N(R10)(R11), —CH2N(R12)C(O)R13, —CH2S(O)2R13, and —CH2S(O)2N(R10)(R11), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, —CH2—C3-10cycloalkyl, C2-9heterocycloalkyl, —CH2—C2-9heterocycloalkyl, C6-10aryl, —CH2—C6-10aryl, —CH2—C1-9heteroaryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups independently selected from halogen, oxo, —CN, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, —OR10, —SR10, —N(R10)(R11), —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)OR13, —N(R12)S(O)2R13, —C(O)R13, —S(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —N(R12)C(O)R13, —S(O)2R13, —S(O)2N(R10)(R11)—, S(═O)(═NH)N(R10)(R11), —CH2C(O)N(R10)(R11), —CH2N(R12)C(O)R13, —CH2S(O)2R13, and —CH2S(O)2N(R10)(R11).
• (b) an additional agent, wherein the additional agent is an anti-cancer agent,
• wherein the combined amount of the compound of Formula (I), or a pharmaceutically acceptable salt thereof and the additional agent is therapeutically effective for treating the cancer.