Compounds targeting mutant of p53

A compound of formula (I), or a stereoisomer, tautomer, deuterated derivative, prodrug or pharmaceutically acceptable salt thereof:

• Y is selected from O, S, NR′, S═O, —S(═O)(═NR′)— or O═S═O;
• one of X1, X2, X3 and X4 is selected from CR2, and the others of X1, X2, X3 and X4 are each independently selected from N or CR4;
• X5 is selected from N or CR1;
• R1 is independently selected from hydrogen, deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl or 5-12 membered heteroaryl;
• said —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, and 5-12 membered heteroaryl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, oxo, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl or 5-12 membered heteroaryl;
• R2 is —NR51R52, —OR53 or —SR54;
• R3 is selected from hydrogen, deuterium, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —S(O)R′, —S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, 5-12 membered heteroaryl;
• said —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, and 5-12 membered heteroaryl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents of R3a;
• each R3a is independently selected from deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, oxo, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(═O)(═NR′)R′, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, 5-12 membered heteroaryl;
• said —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, and 5-12 membered heteroaryl are each independently optionally substituted with one or more substituents R3b,
• each R3b is independently selected from deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, oxo, —OR′, —SR′, —C(O)R′, —C(O N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(═O)(═NR′)R′, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2;
• R4 at each occurrence is independently selected from hydrogen, deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl or 5-12 membered heteroaryl;
• said —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, and 5-12 membered heteroaryl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, oxo, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(═O)(═NR′)R′, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl or 5-12 membered heteroaryl;
• R51, R52, R53 and R54 are each independently selected from hydrogen, deuterium, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —S(O)R′, —S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, 5-12 membered heteroaryl;
• said —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, and 5-12 membered heteroaryl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from deuterium, halogen, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, —C1-6haloalkyl, —CN, oxo, ═NR′, —C1-6alkyl-CH(R′)2, —OR′, —SR′, —C(O)R′, —C(O)N(R′)2, —C(O)OR′, —OC(O)R′, —OC(O)N(R′)2, —N(R′)2, —NR′C(O)R′, —NR′C(O)OR′, —NR′C(O)N(R′)2, —S(O)R′, —S(O)N(R′)2, —NR′S(O)R′, —NR′S(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(═O)(═NR′)R′, —NR′S(O)2R′, —NR′S(O)2N(R′)2, —PO(R′)2, 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkenyl, 6-12 membered aryl, or 5-12 membered heteroaryl;
• R11 and R12 are independently selected from hydrogen, deuterium, —OH, halogen, —CN, oxo, —C1-6 alkyl, —C1-6 haloalkyl, —C1-6alkoxy, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2 or 3-6 membered cycloalkyl;
• wherein said —C1-6alkyl, —C1-6alkoxy and 3-6 membered cycloalkyl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from deuterium, —OH, halogen, —CN, oxo, —C1-6alkoxy, —NH—C1-6alkyl, —N(C1-4 alkyl)2, or 3-6 membered cycloalkyl;
• R13 is selected from hydrogen, deuterium, —C1-6alkyl or 3-6 membered cycloalkyl;
• wherein said —C1-6 alkyl and 3-6 membered cycloalkyl are each independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from deuterium, —OH, halogen, —CN, oxo, —C1-6alkoxy, —NH2, —NC1-6alkyl, or —N(C1_4 alkyl)2;
• each R′ at each occurrence is independently selected from hydrogen, deuterium, halogen, —OH, —CN, oxo, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —C1-6alkyl, —C1-6alkylOC1-6alkyl, —C1-6alkyl-NHC1-6alkyl, —C1-6alkyl-N(C1-6alkyl)2, —C1-6haloalkyl, —OC1-6alkyl, —C3-14cycloalkyl, —C3-14heterocycloalkyl, —C2-6alkenyl, —C2-6alkynyl, 6-12 membered aryl, or 5-12 membered heteroaryl;
• wherein said —C1-6alkyl, —OC1-6alkyl, —C3-14cycloalkyl, —C3-14heterocycloalkyl, —C2-6alkenyl, —C2-6alkynyl, 6-12 membered aryl, or 5-12 membered heteroaryl is independently optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from deuterium, halogen, —CN, —C1-3alkyl, oxo, —OH, —OC1-3alkyl, —NH2, —NHC1-3alkyl, —N(C1-3alkyl)2, —C(═O)NH2, —C(═O)NH(C1-3alkyl), —C(═O)N(C1-3alkyl)2, —S(═O)2NH2, —S(═O)2NH(C1-3alkyl), —S(═O)2C1-3alkyl, —S(═O)2N(C1-3alkyl)2, —S(═O)(═NH)C1-3alkyl, —S(═O)(═NC1-3alkyl)C1-3alkyl, or 3-6 membered cycloalkyl;
• said heterocycloalkyl, heterocycloalkenyl, and heteroaryl each independently contains 1, 2 or 3 heteroatoms selected from N, O, P or S;
• m is selected from 1, 2, 3, 4, 5 or 6.

The compound according to claim 8, wherein R1 is independently selected from —F, —Cl, —C1-3alkyl, —C1-3haloalkyl, 3-6 membered cycloalkyl, 5 membered heteroaryl containing 1 or 2 heteroatoms selected from N, O or S, or 6 membered heteroaryl containing 1 or 2 heteroatoms selected from N;

• said —C1-3alkyl, —C1-3haloalkyl, 3-6 membered cycloalkyl, 5 membered heteroaryl and 6 membered heteroaryl are each independently optionally substituted with 1, 2 or 3 substituents selected from —F, —C1-3alkyl, —OC1-3alkyl, —NH2, —NHC1-3alkyl, —N(C1-3alkyl)2, —CN or 3-6 membered cycloalkyl;
• R51 is selected from
• or —C1-6alkyl, said —C1-6alkyl is optionally substituted with 1, 2, 3, 4, 5, or 6 R5e;
• R5a, R5c and R5d are each independently selected from hydrogen;
• —C1-6alkyl;
• or —C1-6alkyl substituted with 1, 2, 3, 4, 5 or 6 substituents selected from —F, —C1-3alkyl, oxo, —OC1-3alkyl, —NH2, —NHC1-3alkyl, —N(C1-3alkyl)2, —CN or 3-6 membered cycloalkyl;
• R5b and R5e are each independently selected from —F, —C1-6alkyl, oxo, —OC1-6alkyl, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —CN or 111 membered cycloalkyl, wherein, said —C1-6alkyl is optionally substituted with 1, 2, 3 or 4 substituents selected from —F, —C1-3alkyl, oxo, —OC1-3alkyl, —NH2, —NHC1-3alkyl, —N(C1-3alkyl)2, —CN or 3-6 membered cycloalkyl;
• or
• R3 is independently selected from phenyl, 5 membered heteroaryl, or 6 membered heteroaryl;
• said phenyl and heteroaryl at each occurrence is independently optionally substituted with one or more (such as 1, 2, 3, 4, 5 or 6) substituents selected from —F, —CH3, —CD3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2F, —CF3, —CH2CH2F, —CHFCH3, —CF2CH3, —C(CH3)2F, —OH, —O—CH3, —O—CH2CH3, —O—CH2CH2CH3, —O—CH(CH3)2, —C(O)NH2, —C(O)NH(CH3), —C(O)NH(CH2CH3), —C(O)N(CH3)2, —C(O)NH(CH2CH2CH3), —C(O)NH(CH(CH3)2), —C(O)N(CH3)(CH2CH3), —NH2, —NH(CH3), —NH(CH2CH3), —N(CH3)2, —NH(CH2CH2CH3), —NH(CH(CH3)2), —N(CH3)(CH2CH3), —S(O)2H, —S(O)2(CH3), —S(O)2(CH2CH3), —S(O)2(CH3)2, —S(O)2(CH2CH2CH3), —S(O)2(CH(CH3)2), —S(O)2(CH3)(CH2CH3), —S(O)2NH2, —S(O)2NH(CH3), —S(O)2NH(CH2CH3), —S(O)2N(CH3)2, —S(O)2NH(CH2CH2CH3), —S(O)2NH(CH(CH3)2), —S(O)2N(CH3)(CH2CH3), —S(═O)(═NH)CH3, or —S(═O)(═NCH3)CH3, said heterocycloalkyl, heterocycloalkenyl, and heteroaryl each independently contains 1 heteroatom selected from N, O, or S.