Isoindoline compound, preparation method, pharmaceutical composition and use thereof

A compound represented by formula (I) or a tautomer, enantiomer, diastereomer, racemate, isotopic compound, pharmaceutically acceptable salt, ester, or hydrate thereof:

• wherein, X1 is —CH2— or —O—;
• X2 is —CH2— or —CO—;
• R1 is hydrogen, deuterium, fluorine or linear or branched C1-C6 hydrocarbon group;
• R2 and R4 are each independently hydrogen or deuterium;
• R3 is hydrogen, deuterium or halogen;
• L is a substituted or unsubstituted linear alkylene group containing 2-8 carbon atoms, and the “substituted” means that one or more hydrogen atoms in the alkylene group are optionally substituted by the following substituents:
• deuterium, halogen, carbonyl, hydroxyl, amino, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, —NHC(O) Ra1, —NHC(O)ORa2, —NRa3Ra4, wherein Ra1, Ra2, Ra3 and Ra4 are each independently selected from hydrogen, C1-6 alkyl unsubstituted or substituted by halogen, hydroxyl, cyano, or nitro, and C3-6 cycloalkyl unsubstituted or substituted by halogen, hydroxyl, cyano, or nitro;
• Y is absent, —CO— or —CO—NH—, the corresponding placement of Y, A and L is A-L-, A-CO-L-, and A-CO—NH-L-, A is:
• i) heterocyclyl selected from the following:
• X3 is N;
• n4 is 0, 1, 2 or 3;
• n5 is 0, 1, 2 or 3,
• Y1 is hydrogen, deuterium, halogen, cyano, carboxyl, nitro, hydroxyl, amino, aminocarbonyl, C1-C6 alkyl, C1-C6alkoxyl, C1-C6haloalkyl, or C1-C6haloalkoxyl;
• Y2 is substituted or unsubstituted 6-10 membered aryl, or substituted or unsubstituted 6-10 membered heteroaryl, wherein the substituted 6-10 membered aryl or 6-10 membered heteroaryl is substituted by one or more substituents selected from:
• deuterium, halogen, cyano, nitro, hydroxyl, aminocarbonyl, C1-C3 alkyl, C1-C3 alkoxyl, C1-C3alkylcarbonyl, C1-C3alkoxycarbonyl, C1-C3alkylsulfonyl, C1-C3alkylaminocarbonyl, C3-C6 cycloalkyl or heterocyclyl, C1-C3 acylamino, C1-C3 haloalkyl, C1-C3haloalkoxyl;
• Y3 is substituted or unsubstituted 6-10 membered aryl, or substituted or unsubstituted 6-10 membered heteroaryl, wherein the substituted 6-10 membered aryl or 6-10 membered heteroaryl is substituted by one or more substituents selected from:
• deuterium, halogen, cyano, nitro, hydroxyl, aminocarbonyl, C1-C3 alkyl, C1-C3 alkoxyl, C1-C3alkylcarbonyl, C1-C3alkoxycarbonyl, C1-C3alkylsulfonyl, C1-C3alkylaminocarbonyl, C3-C6 cycloalkyl or heterocyclyl, C1-C3 acylamino, C1-C3 haloalkyl, C1-C3haloalkoxyl;
• Y4 and Y5 are absent, or one or more substituents on the heterocyclic ring, Y4 and Y5 are each independently deuterium, halogen, oxo, C1-C3 alkyl, C3 cycloalkyl, C1-C3 haloalkyl or phenyl;
• ii) fused heterocyclyl selected from:
• X4 is C, N or O;
• n6 is 0, 1, 2 or 3;
• n7 is 0, 1, 2 or 3;
• n8 is 0, 1, 2, 3 or 4;
• is 6-10 membered aryl ring or 5-10 membered heteroaryl ring;
• R8 is each independently selected from hydrogen, deuterium, C1-C3 alkoxyl, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, carboxyl, C1-Czalkylaminocarbonyl, C1-C3alkoxycarbonyl, nitro, amino, cyano, C1-C3 haloalkyl, hydroxyl, C1-C3alkylsulfonyl, C1-C3 alkylamino, C1-C3 acylamino, aminocarbonyl, C3-C6 heterocyclyl, C1-C3haloalkoxyl, phenyl or 5-6 membered heteroaryl;
• with the proviso that when Ra is selected from the following substituents:
• hydrogen, deuterium, C1-C3 alkoxyl, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, carboxyl, C1-C3 alkyl aminocarbonyl, C1-C3alkoxycarbonyl, nitro, amino, cyano, C1-C3 haloalkyl, hydroxyl, C1-C3alkylsulfonyl, and Y is absent, then X1 is other than —O—;
• Y6 and Y7 are absent, or one or more substituents on the heterocyclic ring independently selected from deuterium, halogen, C1-C3 alkyl, C3 cycloalkyl, C1-C3 haloalkyl;
• or iii) spiroheterocyclic group selected from:
• nc1 is 0, 1, 2 or 3;
• nc2 is 0, 1, 2 or 3;
• nc3 is 1, 2 or 3;
• n9 is 0, 1, 2, 3 or 4;
• is 6-10 membered aryl ring or 5-10 heteroaryl ring;
• R9 is independently selected from the following substituents:
• deuterium, halogen, cyano, nitro, hydroxyl, amino, C1-C3 alkylamino, C1-C3 acylamino, aminocarbonyl, linear or branched C1-C6 alkyl, linear or branched C1-C6 alkoxyl, C3-C6cycloalkyloxyl, C3-C6 cycloalkyl or heterocycloalkyl, C1-C3alkylaminocarbonyl, C1-C3alkoxycarbonyl, C1-C3alkylsulfonyl, C1-C3 haloalkyl, C1-C3haloalkoxyl, phenyl, 5-6 membered heteroaryl;
• R10 and R11 are independently selected from hydrogen, substituted or unsubstituted 6-10 membered aryl, substituted or unsubstituted 5-10 membered heteroaryl, and the species of substituent is the same as the above-mentioned substituent R9 on the
• ring;
• Y8 is a substituent which optionally replaces the hydrogen atom in the non-aromatic moiety of the spiro ring structure, and Y8 is optionally substituted by deuterium, halogen, C1-C3 alkyl, C3 cycloalkyl or C1-C3 haloalkyl.