Ezh1/2 inhibitor, preparation thereof, and use thereof in anti-tumor therapy

A compound represented by Formula I or Formula II, or a deuterated compound thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:

• wherein,
• X is selected from a group consisting of single bond, O, NRX1 or CHRX2;
• Y is selected from a group consisting of O, S, NRY1 or CHRY2;
• Z is selected from a group consisting of C═O, O, S, NRZ1 or CHRZ2;
• Q is selected from a group consisting of single bond, O or S;
• when X is single bond, Y and Z are not both O;
• RX1 is selected from a group consisting of the following groups:
• hydrogen, —C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• RX2 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• RY1 is selected from a group consisting of the following groups:
• hydrogen, —C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• RY2 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• RZ1 is selected from a group consisting of the following groups:
• hydrogen, C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• RZ2 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R1 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, amino, hydroxyl, —C1˜6alkyl, —O(C1˜6alkyl), halo-C1˜6alkyl, —C0˜2alkylene-OR1b, —C0˜2alkylene-C(O)R1b, —C0˜2alkylene-C(O)NR1bR1c—C0˜2alkylene-NR1bR1c—C0˜2alkylene-NR1bC(O)R1c, —C0˜4alkylene-S(O)2R1b, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• wherein said alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl ring, heteroaryl ring is optionally further substituted by one, two or three independent R1b;
• R1b, R1c is each independently selected from a group consisting of the following groups:
• hydrogen, —OH, C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R2 is selected from a group consisting of the following groups:
• —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl);
• wherein said alkylene, cycloalkyl, heterocycloalkyl is optionally further substituted by one, two or three independent R2b;
• R2b is each independently selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, amino, hydroxyl, —C1˜6alkyl, —O(C1˜6alkyl), halo-C1˜6alkyl, —C0˜2alkylene-OR2c, —C0˜2alkylene-C(O)R2c, —C0˜2alkylene-C(O)NR2cR2d, —C0˜2alkylene-NR2cR2d, —C0˜2alkylene-NR2cC(O)R2d, —C0˜4alkylene-S(O)2R2c, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl ring, heteroaryl ring is optionally further substituted by one, two or three independent R2c;
• R2c, R2d is each independently selected from a group consisting of hydrogen, cyano, nitro, —OH, halogen, —C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-O(C1˜6alkyl), —O(halo-C1˜6alkyl), —O(3˜10 membered cycloalkyl), —O(3˜10 membered heterocycloalkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• wherein said alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl ring, heteroaryl ring is optionally further substituted by one, two or three independent R2e;
• R2e is each independently selected from a group consisting of hydrogen, cyano, nitro, —OH, halogen, —C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-O(C1˜6alkyl), —O(halo-C1˜6alkyl), —O(3˜10 membered cycloalkyl), —O(3˜10 membered heterocycloalkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R3 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, amino, —OH, —C1˜6alkyl, —O(C1˜6alkyl), halo-C1˜6alkyl, —C0˜2alkylene-OR3b, —C0˜2alkylene-C(O)R3b, —C0˜2alkylene-C(O)NR3bR3c, —C0˜2alkylene-NR3bR3c, —C0˜2alkylene-NR3bC(O)R3c, —C0˜4alkylene-S(O)2R3b, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl);
• R3b, R3c is each independently selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, —OH, C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R4 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• wherein said alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl ring, heteroaryl ring is optionally further substituted by one, two or three independent R4b;
• R4b is each independently selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, —OH, C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R5 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R6 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, hydroxyl, —C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R7 is selected from a group consisting of the following groups:
• hydrogen, —C1˜6alkyl, halo-C1˜6alkyl, —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• R8 is selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, —OH, C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring);
• or, R7, R8 and the atom directly bound thereto form a 4-10 membered heterocyclic ring;
• wherein said heterocyclic ring is optionally further substituted by one, two or three independent R71;
• each R71 is each independently selected from a group consisting of the following groups:
• hydrogen, halogen, cyano, nitro, —OH, C1˜6alkyl, halo-C1˜6alkyl, —O(C1˜6alkyl), —O(halo-C1˜6alkyl), —NH2, —NH(C1˜6alkyl), —N(C1˜6alkyl) (C1˜6alkyl), —C0˜2alkylene-(3˜10 membered cycloalkyl), —C0˜2alkylene-(3˜10 membered heterocycloalkyl), —C0˜2alkylene-(5˜10 membered aryl ring), —C0˜2alkylene-(5˜10 membered heteroaryl ring).