Heterocyclic compound having anti-tumor activity and use thereof

A compound represented by formula (A), or a stereoisomer, optical isomer, pharmaceutical salt, prodrug, solvate or isotope derivative thereof,

• wherein represents a single bond or a double bond;
• Y and Z are both C or N, where Z is C when Y is N and Z is N when Y is C;
• Y and Z together with the atoms to which they are linked form a ring A, where the ring A is 5- to 12-membered heterocyclyl or 5- to 12-membered heteroaryl;
• there is one, two or three R2, each of which at each occurrence is independently hydrogen, halogen, hydroxyl, cyano, amino, nitro, formyl, oxo, C1-6 alkyl, C1-6 alkoxy, —C1-6 alkyl-NH(C1-6 alkyl), —C1-6 alkyl-N(C1-6 alkyl)2, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C1-6 alkoxy, —C1-6 alkyl-NH(C1-6 alkyl), —C1-6 alkyl-N(C1-6 alkyl)2, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more cyano, hydroxyl or halogen;
• R3 is hydrogen, halogen, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, and 3- to 6-membered heterocyclyl are all optionally substituted with one or more hydroxyl or halogen;
• ring B is C4-12 cycloalkyl, C4-12 cycloalkenyl, 4- to 12-membered heterocyclyl, C6-12 aryl, 5- to 12-membered heteroaryl, C6-12 aryl-fused C4-12 cycloalkyl, C6-12 aryl-fused 4- to 12-membered heterocyclyl or C6-12 aryl-fused C4-12 cycloalkenyl;
• each of R4, if present, is independently hydrogen, cyano, halogen, amino, hydroxyl, oxo, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, —C0-6 alkyl-NH—C1-6 alkyl, —C0-6 alkyl-N(C1-6 alkyl)(C1-6 alkyl), C3-6 cycloalkyl, C3-6 halocycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, —C0-6 alkyl-NH—C1-6 alkyl, —C0-6 alkyl-N(C1-6 alkyl)(C1-6 alkyl), C3-6 cycloalkyl, C3-6 halocycloalkyl, and 3- to 6-membered heterocyclyl are all optionally substituted with one or more of the following substituents:
• halogen, hydroxyl, amino, —SO2—C1-4 alkyl or oxo;
• w is 0, 1, 2, 3 or 4;
• when is a double bond, X is C, and R1 linked thereto is —O—RA, —N(RD)RB or RC;
• when R1 is —O—RA, RA is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with 1 to 3 identical or different Ra1;
• each of Ra1, if present, is independently halogen, hydroxyl, cyano, amino, nitro, oxo, formyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —COC1-6 alkyl, —CH2COC1-6 alkyl, —CH2CON(C1-6 alkyl)2, —CH2CONHC1-6 alkyl, —NHC1-6 alkyl, —NHC1-6 alkyl)2, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl;
• when R1 is —N(RD)RB, RB is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with 1 to 3 identical or different Rb1;
• each of Rb1, if present, is independently halogen, hydroxyl, cyano, amino, nitro, oxo, formyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —COC1-6 alkyl, —CH2COC1-6 alkyl, —CH2CON(C1-6 alkyl)2, —CH2CONHC1-6 alkyl, —NHC1-6 alkyl, —NHC1-6 alkyl)2, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl;
• RD is hydrogen, halogen, hydroxyl, cyano, amino, nitro, oxo, formyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —COC1-6 alkyl, —CH2COC1-6 alkyl, —CH2CON(C1-6 alkyl)2, —CH2CONHC1-6 alkyl, —NHC1-6 alkyl or —NHC1-6 alkyl)2;
• when R1 is RC, RC is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with 1 to 4 identical or different Rc1;
• each of Rc1, if present, is independently halogen, hydroxyl, cyano, amino, nitro, oxo, formyl, methylsulfonyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —COC1-6 alkyl, —COC3-6 cycloalkyl, —CH2COC1-6 alkyl, —CH2CON(C1-6 alkyl)2, —CH2CONHC1-6 alkyl, —NHC1-6 alkyl, —NHC1-6 alkyl)2, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —COC1-6 alkyl, —COC3-6 cycloalkyl, —CH2COC1-6 alkyl, —CH2CON(C1-6 alkyl)2, —CH2CONHC1-6 alkyl, —NHC1-6 alkyl, —NHC1-6 alkyl)2, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more substituents selected from deuterium, hydroxyl, cyano, C1-3 alkyl, C1-3 alkoxy or halogen;
• when is a single bond, X is N, and R1 linked thereto is C3-10 cycloalkyl, C3-10 cycloalkenyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C3-10 cycloalkyl, C3-10 cycloalkenyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more identical or different Ra4 and/or Rb4;
• each of Ra4, if present, is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more identical or different Rb4 and/or Rc4;
• each of Rb4, if present, is independently —ORc4, —NRc4Rc4, halogen, —CN, —C(O)Rc4, —C(O)ORc4, —C(O)NRc4Rc4, —OC(O)Rc4, —S(O)2Rc4, —S(O)2NRc4Rc4, —NHC(O)Rc4, —N(C1-4 alkyl)C(O)Rc4, —NHC(O)ORc4 or a divalent substituent ═O or ═NH, where the ═O and ═NH may only be substituents in a non-aromatic ring system;
• each of Rc4, if present, is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more identical or different Rd4 and/or Re4;
• each of Rd4, if present, is independently —ORe4, —NRe4Re4, halogen, —CN, —C(O)Re4, —C(O)ORe4, —C(O)NRe4Re4, —S(O)2Re4, —S(O)2NRe4Re4, —NHC(O)Re4, —N(C1-4 alkyl)C(O)Re4 or a divalent substituent ═O, where the ═O may only be a substituent in a non-aromatic ring system;
• each of Re4, if present, is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl are all optionally substituted with one or more hydrogen, cyano, hydroxyl or halogen;
• wherein Z and Y are deemed as the atoms of ring A and counted in the number of the atoms of ring A;
• unless otherwise stated, heteroatoms in the heteroaryl and heterocyclyl are each independently O, N or S, and the number of heteroatoms is 1, 2, 3 or 4;
• optionally, the compound has a structure represented by formula (A′):
• the substituents in formula (A′) are as defined in formula (A).