Benzodiazepine compounds, and preparation method therefor and use thereof

A benzodiazepine compound, comprising a compound represented by general formula (I), and a pharmaceutically acceptable salt, a stereoisomer, a tautomer, a polymorph, a solvate, a metabolite or a prodrug thereof:

• wherein:
• R1 is selected from hydrogen, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is each optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, amino, nitro, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• R2 is located at any position of the benzene ring and is monosubstituted or polysubstituted;
• R2 is selected from hydrogen, halogen, hydroxy, cyano, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, trifluoromethyl, nitro, amino, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is each optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, amino, nitro, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• X is selected from C and N, and when X is C, R3 is selected from hydrogen, halogen, hydroxy, cyano, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, trifluoromethyl, nitro, amino, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is each optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, amino, nitro, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• when X is N, the R3 substituent is absent;
• R4 is located at any position of the benzene ring or the pyridine ring and is monosubstituted or polysubstituted;
• R4 is selected from hydrogen, halogen, hydroxy, cyano, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, trifluoromethyl, nitro, amino, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is substituted with substituents independently selected from halogen, hydroxy, cyano, amino, nitro, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• R5 is selected from hydrogen, C1-20 alkyl, C1-20 acyl, C2-20 alkenyl, C2-20 alkynyl, C1-10 alkylene-phosphate group, P(O)(OH)2-C1-10 alkylene, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C1-20 acyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is substituted with substituents selected from halogen, oxo (═O), C1-10 alkylene-halogen, hydroxy, C1-10 alkylene-hydroxy, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, cyano, C1-10 alkylene-cyano, nitro, C1-10 alkylene-nitro, amino, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• R6 or R7 are selected from hydrogen, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is each optionally substituted with one or more substituents independently selected from halogen, C1-10 alkylene-halogen, hydroxy, C1-10 alkylene-hydroxy, (R6)(R7)N—(CH2)n—, cyano, C1-10 alkylene-cyano, nitro, C1-10 alkylene-nitro, amino, C1-20 alkyl, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• n is selected from 1 to 20;
• W is selected from hydrogen, halogen, hydroxy, cyano, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, trifluoromethyl, nitro, amino, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, or 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl is selected from halogen, C1-10 alkylene-halogen, hydroxy, C1-10 alkylene-hydroxy, R6R7N—(CH2)n—, (R6)(R7)N—(CH2)n—, cyano, C1-10 alkylene-cyano, nitro, C1-10 alkylene-nitro, amino, C1-20 alkyl, C, C1-20 alkoxy, C2-20 alkenyl, C2-20 alkynyl, 3- to 10-membered cycloalkyl or C1-10 alkylene-3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl or C1-10 alkylene-3- to 10-membered heterocyclyl, 6- to 14-membered aryl or C1-10 alkylene-6- to 14-membered aryl, and 5- to 14-membered heteroaryl or C1-10 alkylene-5- to 14-membered heteroaryl;
• wherein the hydrogen described above and the hydrogen contained in the groups described above are selected from protium, deuterium, and tritium.