Parp inhibitor, pharmaceutical composition comprising same, and use thereof

A compound or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, metabolite, isotopically labeled compound or prodrug thereof, wherein the compound has the structure of Formula (I):

• wherein:
• is a single bond or a double bond;
• X is N or CR5;
• Y is N or CR5′;
• Z is CR6 or N;
• when is a single bond, V is CR7RA or NRA;
• when is a double bond, V is CRA;
• RA is selected from the group consisting of H, halogen, —OH, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb, —O—C1-6 alkylene-NRaRb and
• ring A is a C3-6 hydrocarbon ring, 3- to 10-membered heterocycle, C6-10 aromatic ring or 5- to 14-membered heteroaromatic ring;
• R and R′, at each occurrence, are each independently selected from the group consisting of H, halogen, —OH, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb and —O—C1-6 alkylene-NRaRb;
• preferably, R and R′ are each independently selected from the group consisting of H, —CN and C1-6 alkyl;
• R1 and R2 are each independently selected from the group consisting of halogen, —OH, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb and —O—C1-6 alkylene-NRaRb;
• R3, at each occurrence, is each independently selected from the group consisting of halogen, —OH, ═O, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb and —O—C1-6 alkylene-NRaRb;
• when m>1, two R3 groups optionally together form —C1-6 alkylene- or —C2-6 alkenylene-, the alkylene chain and alkenylene chain are optionally interrupted by one or more groups independently selected from the group consisting of 0, C(═O), C(═O)O, NR, S, S═O and S(═O)2;
• or, R3 and RA together with the groups to which they are attached optionally form a C3-6 hydrocarbon ring, 3- to 10-membered heterocycle, C6-10 aromatic ring or 5- to 14-membered heteroaromatic ring;
• R4, at each occurrence, is each independently selected from the group consisting of halogen, —OH, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb and —O—C1-6 alkylene-NRaRb;
• when two R4 groups are ortho to each other on ring A, the two R4 groups together with the groups to which they are attached optionally form 3- to 10-membered heterocycle or 5- to 14-membered heteroaromatic ring;
• or, R3 and R4 together with the groups to which they are attached optionally form a C3-6 hydrocarbon ring, 3- to 10-membered heterocycle, C6-10 aromatic ring or 5- to 14-membered heteroaromatic ring;
• R5, R5′, R6 and R7, at each occurrence, are each independently selected from the group consisting of H, halogen, —OH, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-CN, —C1-6 alkylene-ORa, —C1-6 alkylene-NRaRb and —O—C1-6 alkylene-NRaRb;
• Ra and Rb, at each occurrence, are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-10 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
• the above alkyl, alkylene, haloalkyl, alkenyl, alkenylene, hydrocarbon ring, cyclic hydrocarbyl, heterocycle, heterocyclyl, aryl, aromatic ring, heteroaryl, heteroaromatic ring and aralkyl, at each occurrence, are each optionally substituted with one or more substituents independently selected from the group consisting of:
• halogen, —OH, ═O, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —C(═O)Rc, —OC(═O)Rc, —C(═O)ORc, —ORc, —SRc, —S(═O)Rc, —S(═O)2Rc, —S(═O)2NRcRd, —NRcRd, —C(═O)NRcRd, —NRc—C(═O)Rd, —NRc—C(═O)ORd, —NRc—S(═O)2—Rd, —NRc—C(═O)—NRcRd, —C1-6 alkylene-ORc, —C1-6 alkylene-NRcRd and —O—C1-6 alkylene-NRcRd, the alkyl, alkylene, haloalkyl, cyclic hydrocarbyl, heterocyclyl, aryl, heteroaryl and aralkyl are further optionally substituted with one or more substituents independently selected from the group consisting of:
• halogen, —OH, ═O, —NH2, —CN, —NO2, C1-6 alkyl, C1-6 haloalkyl, C3-6 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
• Rc and Rd, at each occurrence, are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C3-10 cyclic hydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
• and
• m and n are each independently an integer of 0, 1, 2, 3, or 4.