3clpro protease inhibitor

A compound of formula (I), or an isomer or a pharmaceutically acceptable salt thereof,

• wherein, ring A is selected from the group consisting of C6-10 aryl, 5- to 10-membered heteroaryl, C3-12 cycloalkyl, and 3- to 12-membered heterocyclyl;
• X is selected from the group consisting of —(CH2)s—C(═O)—and —NH—C(═O)—;
• Y is NH or a chemical bond;
• ring B is selected from the group consisting of C3-12 cycloalkyl, 3- to 12-membered heterocyclyl, and 5- to 10-membered heteroaryl;
• Z is selected from the group consisting of —O—, —S—, —CH2—, —C(═O)—NH—and —(CH2)tNH—;
• ring C is selected from the group consisting of C6-10 aryl and 5- to 10-membered heteroaryl;
• ring D is selected from the group consisting of 3- to 12-membered heterocyclyl and 5- to 6-membered heteroaryl;
• or ring D is absent;
• R1 is selected from the group consisting of halogen, OH, O, cyano, —NR1aR1b, C1-4 alkyl, C1-4 alkoxy, C3-8 cycloalkyl, C6-10 aryl, —NR1aCOR1c, —SR1d, and —CONR1aR1b, wherein C1-4 alkyl and C1-4 alkoxy can be further substituted by one or more halogens;
• R1a, R1b, R1e, and R1d are each independently selected from the group consisting of H, C1-4 alkyl and halo-C1-4 alkyl, wherein C1-4 alkyl can be substituted by one or more deuteriums;
• or, two R1 linked to the same C atom on ring A can together form —CH2, ═S, or C3-5 cycloalkyl;
• R2 is selected from the group consisting of deuterium, cyano, C2-4 alkynyl, halogen, C1-4 alkyl, hydroxyl, C1-4 alkoxy, deutero-C1-4 alkoxy, —C(═O)—NR2aR2b, —C2-4 alkynyl-R2c, 5- to 6-membered heteroaryl and —O—(CH2)y—R2d,
• R2c is selected from the group consisting of 5- to 6-membered heteroaryl, wherein 5- to 6-membered heteroaryl can be further substituted by C1-4 alkyl;
• R2a and R2b are each independently selected from the group consisting of H, C1-4 alkyl, phenyl, 5- to 9-membered heteroaryl, 5- to 6-membered heterocyclyl, and C3-5 cycloalkyl, wherein C1-4 alkyl, phenyl, 5- to 9-membered heteroaryl, 5- to 6-membered heterocyclyl, and C3-5 cycloalkyl can be further substituted by one or more substituents selected from the group consisting of methyl, ethyl, cyclopropyl, halogen, CF3, —CH2CF3, phenyl, methoxy, pyridinyl, pyrimidinyl, tetrahydropyranyl, and —CH2CH2OCH3, wherein pyridinyl, pyrimidinyl, and tetrahydropyranyl can be further substituted by one or more methyl, CF3, halogen, —NHCH3, or —CHF2;
• or, R2a, R2b and their linked N atom together form 4- to 9-membered heterocyclyl or 5- to 9-membered heteroaryl, wherein 4- to 9-membered heterocyclyl and 5- to 9-membered heteroaryl can be further substituted by one or more substituents selected from the group consisting of C1-4 alkyl, halogen, hydroxyl, and —CH2CH2OCH3;
• R2d is selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, phenyl, 5- to 6-membered heteroaryl and 5- to 6-membered heterocyclyl, wherein phenyl, 5- to 6-membered heteroaryl and 5- to 6-membered heterocyclyl can be further substituted by one or more substituents selected from the group consisting of halogen, C1-4 alkyl, C1-4 alkoxy, and halo-C1-4 alkyl;
• y is 0, 1, or 2;
• R3 is selected from the group consisting of nitro, halogen, hydroxyl, cyano, C1-4 alkyl, halo-C1-4 alkyl, —NR3aR3b and —N(R3aR3bR3c)+;
• R3a, R3b and R3c are each independently selected from the group consisting of H and C1-4 alkyl;
• R4 is selected from the group consisting of halogen, hydroxyl, C1-4 alkyl, halo-C1-4 alkyl, 3- to 8-membered heterocyclyl, —C(═O)R4a, —NHC(═O)R4a, —(CH2)rOR4b, —NR4cR4d, C1-4 alkoxy,—(CH2)x—C3-6 cycloalkyl, —NR4a—(CH2)x—C6-10 aryl, wherein aryl can be further substituted by halogen;
• R4a, R4b, R4c, and R4d are each independently selected from the group consisting of H, C1-4 alkyl, halo-C1-4 alkyl, 5- to 6-membered heterocyclyl and C3-6 cycloalkyl;
• or R4c, R4d and their linked N atom together form 6-membered heterocyclyl;
• x is 0, 1, or 2;
• r is 0, 1, 2, or 3;
• m, n, p, and q are each independently 0, 1, 2, 3, 4, or 5;
• and
• s and t are each independently 0 or 1.