Immunomodulator

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

• wherein represents a single bond or a double bond;
• X1 is C or N;
• X2 and X3 are independently selected from the group consisting of O, N, NRX and CRX;
• X4 and X5 are each independently C or N;
• each RX is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, —C1-6 alkyl, —OC1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —O(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —O(4 to 10-membered heterocycloalkyl), deuterium-substituted —C1-6 alkyl and halogen-substituted —C1-6 alkyl;
• Y1, Y2 and Y3 are each independently N or CRY;
• each RY is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-OC1-6 alkyl, —C0-2 alkylene-O(halogen-substituted —C1-6 alkyl), —C0-2 alkylene-O(3 to 10-membered cycloalkyl) and —C0-2 alkylene-O(4 to 10-membered heterocycloalkyl);
• Z is C(O), S(O) or S(O)2;
• R1 is selected from the group consisting of —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C2-6 alkenyl, halogen-substituted —C2-6 alkenyl, —C2-6 alkynyl, halogen-substituted —C2-6 alkynyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring), —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), —C0-2 alkylene-OR11 and —C0-2 alkylene-NR11R12, wherein alkylene, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R1a;
• R11 and R12 are independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R1a;
• each R1a is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-4 alkylene-OR1b, —C0-4 alkylene-SR1b, —C0-2 alkylene-C(O)R1b, —C0-2 alkylene-C(O)NR1bR1c, —C0-4 alkylene-NR1bR1c, —C0-2 alkylene-NR1bC(O)R1c, —C0-4 alkylene-S(O)2R1b, —C0-4 alkylene-NHS(O)2R1b, —C0-4 alkylene-S(O)R1b, —C0-4 alkylene-(3 to 10-membered cycloalkyl), —C0-4 alkylene-(4 to 10-membered heterocycloalkyl), —C0-4 alkylene-(5 to 10-membered aromatic ring) and —C0-4 alkylene-(5 to 10-membered heteroaromatic ring), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R1d;
• or two R1a linked to the same carbon atom form 3 to 10-membered cycloalkyl or 4 to 10-membered heterocycloalkyl with the carbon atom, wherein cycloalkyl and heterocycloalkyl are unsubstituted or substituted by one, two or three R1e;
• R1b, R1c and R1d are independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, halogen, cyano, ═O, ═S, nitro, —OH, —SH, —S(C1-6 alkyl), —C0-2 alkylene-O(C1-6 alkyl), —C(O)NH2, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring);
• each R1e is independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, halogen, cyano, ═O, ═S, nitro, —OH, —SH, —S(C1-6 alkyl), —C0-2 alkylene-O(C1-6 alkyl), —C(O)NH2, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(6 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring);
• R2 is selected from the group consisting of —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 12-membered bridged cycloalkyl), —C0-2 alkylene-(5 to 12-membered bridged heterocycloalkyl), —C0-2 alkylene-(5 to 12-membered spiro cycloalkyl), —C0-2 alkylene-(5 to 12-membered spiro heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring), —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), —C0-2 alkylene-OR21, —C0-2 alkylene-NR21R22 and —C0-2 alkylene-CN, wherein alkylene, cycloalkyl, heterocycloalkyl, bridged cycloalkyl, bridged heterocycloalkyl, spiro cycloalkyl, spiro heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two, three or four R2a;
• R21 and R22 are independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R2a;
• and
• each R2a is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, ═O, ═S, nitro, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-OR2b, —C0-2 alkylene-C(O)R2b, —C0-2 alkylene-C(O)NR2bR2c, —C0-2 alkylene-NR2bR2c, —C0-2 alkylene-NR2bC(O)R2c, —C0-4 alkylene-S(O)2R2b, —C0-4 alkylene-CN, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 12-membered bridged cycloalkyl), —C0-2 alkylene-(5 to 12-membered bridged heterocycloalkyl), —C0-2 alkylene-(5 to 12-membered spiro cycloalkyl), —C0-2 alkylene-(5 to 12-membered spiro heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, bridged cycloalkyl, bridged heterocycloalkyl, spiro cycloalkyl, spiro heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R2d;
• or two R2a linked to the same carbon atom form 3 to 10-membered cycloalkyl or 4 to 10-membered heterocycloalkyl with the carbon atom;
• R2b and R2c are independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R2d;
• each R2d is independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, halogen, cyano, ═O, ═S, nitro, —OH, —O(C1-6 alkyl), —NH2, —NH(C1-6 alkyl) and —N(C1-6 alkyl)(C1-6 alkyl);
• R3 is selected from the group consisting of hydrogen, deuterium, halogen, cyano, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring), —C0-2 alkylene-(5 to 10-membered heteroaromatic ring), —C0-2 alkylene-OR31 and —C0-2 alkylene-NR31R32, wherein alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three R3a;
• R31 and R32 are independently selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring) and —C0-2 alkylene-(5 to 10-membered heteroaromatic ring);
• each R3a is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, ═O, ═S, nitro, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl and halogen-substituted —C1-6 alkyl;
• L is —C2-6 alkylene or —C2-6 alkenylene, wherein one, two or three methylene groups in —C2-6 alkylene and —C2-6 alkenylene are unsubstituted or substituted by O, NRL1, C(O), S(O) or S(O)2, or —C2-6 alkylene and —C2-6 alkenylene are unsubstituted or substituted by one, two, three or four RL;
• each RL1 is selected from the group consisting of hydrogen, deuterium, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-OC1-6 alkyl, —C0-2 alkylene-CN, —C0-2 alkylene-C(O)(C1-6 alkyl), —C0-2 alkylene-O(3 to 10-membered cycloalkyl), —C0-2 alkylene-O(4 to 10-membered heterocycloalkyl), —C0-2 alkylene-(3 to 10-membered cycloalkyl), —C0-2 alkylene-(3 to 10-membered heterocycloalkyl), —C0-2 alkylene-(5 to 10-membered aromatic ring), —C0-2 alkylene-(5 to 10-membered heteroaromatic ring) and —C0-4 alkylene-N(C1-6 alkyl)(C1-6 alkyl), wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aromatic ring and heteroaromatic ring are unsubstituted or substituted by one, two or three RL2;
• each RL2 is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, ═O, ═S, nitro, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl and halogen-substituted —C1-6 alkyl;
• and
• each RL is independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, ═O, ═S, nitro, —C1-6 alkyl, deuterium-substituted —C1-6 alkyl, halogen-substituted —C1-6 alkyl, —C0-2 alkylene-OC1-6 alkyl, —C0-2 alkylene-O(3 to 10-membered cycloalkyl) and —C0-2 alkylene-O(4 to 10-membered heterocycloalkyl);
• or two RL linked to the same carbon atom form 3 to 10-membered cycloalkyl or 4 to 10-membered heterocycloalkyl with the carbon atom.