P2X3 and/or P2X2/3 receptor antagonist, pharmaceutical composition containing same, and use thereof

A compound, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, wherein the compound has the structure of any of the following formulae:

• R4 and R5 are each independently selected from the group consisting of H, —C(═O)ORa, —NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —C1-6 alkylene-NRaRb, —C1-6 alkylene-ORa, —C1-6 alkylene-O—C1-6 alkylene-ORa, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
• the above alkyl, alkylene, alkenyl, alkynyl, cyclic hydrocarbyl, heterocyclyl, aryl, heteroaryl and aralkyl, at each occurrence, are each optionally substituted with one or more substituents independently selected from the group consisting of:
• halogen, hydroxyl, oxo, amino, cyano, nitro, —Si(R)3, C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-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-NRaRb, —C1-6 alkylene-ORa, —C1-6 alkenylene-ORa and —O—C1-6 alkylene-NRaRb, the alkyl, cyclic hydrocarbyl, heterocyclyl, aryl, heteroaryl and aralkyl are further optionally substituted with one or more substituents independently selected from the group consisting of:
• halogen, hydroxyl, oxo, amino, cyano, nitro, —NRaRb, C1-6 alkyl, —O—C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
• Ra and Rb, at each occurrence, are each independently selected from the group consisting of H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
• alternatively, Ra and Rb together with the atom to which they are attached form a 3-12-membered heterocycle or heteroaromatic ring, and the above groups are further optionally substituted with one or more substituents independently selected from the group consisting of:
• halogen, hydroxyl, oxo, amino, cyano, nitro, C1-6 alkyl, —O—C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
• and
• R and R′, at each occurrence, are each independently selected from the group consisting of H, SEM, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl, and at most 2 ring members in the cyclic hydrocarbyl and heterocyclyl are C(═O).