Isoindoline derivative, pharmaceutical composition and use thereof

1. A compound of formula I, or a pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof,

wherein, the carbon atom labelled by * is an asymmetric center;

R 1 and R 2 are independently H, D, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 3 -C 6 )cycloalkyl, R 6 —S(O) 2 — or R 6 —C(O)—;

R 6 is substituted or unsubstituted (C 3 -C 6 )cycloalkyl; or (C 1 -C 6 )alkyl, which is optionally substituted with one or more groups selected from D, halogen, hydroxyl, amino, (C 1 -C 6 )alkyl amino, (C 1 -C 6 )alkoxy and benzyloxy;

X 1 , X 2 , X 3 , X 4 , and X 5 are independently CH, CD, or CR 7 ;

X 6 is N;

R 7 is halogen or cyano;

R 3 and R 4 are independently H, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 3 -C 6 )cycloalkyl, or, substituted or unsubstituted (C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl;

R 5 is substituted or unsubstituted (C 1 -C 6 )alkyl;

R 10 , R 11 and R 12 are independently H or D;

the substituent in substituted (C 1 -C 6 )alkyl, substituted (C 3 -C 6 )cycloalkyl, or, substituted (C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl is one or more selected from the group consisting of: D, halogen, hydroxyl, amino, (C 1 -C 6 )alkyl amino, (C 1 -C 6 )alkoxy and benzyloxy; when there are a plurality of substituents, the substituents are the same or different.

2. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

X 6 is N, X 1 , X 2 , X 3 are independently CH, CD or CR 7 , X 4 , X 5 are independently CH, CD; or

X 6 is N, X 1 is CR 7 , X 2 , X 3 , X 4 and X 5 are independently CH or CD; or

X 6 is N, X 2 is CR 7 , X 1 , X 3 , X 4 and X 5 are independently CH or CD; or

X 6 is N, X 3 is CR 7 , X 1 , X 2 , X 4 and X 5 are independently CH or CD.

3. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

one of R 1 and R 2 is H or D, the other is R 6 —S(O) 2 — or R 6 —C(O)—.

4. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 6 is (C 3 -C 6 )cycloalkyl; or (C 1 -C 4 )alkyl, which is optionally substituted with one or more substituents selected from the group consisting of D, halogen, hydroxyl, amino, (C 1 -C 4 )alkyl amino, (C 1 -C 4 )alkoxy, and benzyloxy.

5. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 3 and R 4 are independently H, or substituted or unsubstituted (C 1 -C 6 )alkyl.

6. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 5 is methyl, ethyl, propyl, isopropyl, CD 3 , CH 2 D, CHD 2 , C 2 D 5 or CH 2 CD 3 .

7. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 7 is fluorine, chlorine, bromine or cyano.

8. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein

X 1 , X 2 , X 3 , X 4 and X 5 are independently CH or CR 7 .

9. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 10 and R 11 are H.

10. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 12 is H.

11. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

the asymmetric center refers to (S)-configured carbon.

12. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein, the compound of formula I is any one of the following compounds:

13. A compound of formula I-3:

wherein,

X 1 , X 2 , X 3 , X 4 , and X 5 are independently CH, CD, or CR 7 ;

X 6 is N;

R 7 is halogen or cyano;

R 3 and R 4 are independently H, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 3 -C 6 )cycloalkyl, or, substituted or unsubstituted (C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl;

R 5 is substituted or unsubstituted (C 1 -C 6 )alkyl;

R 10 , R 11 and R 12 are independently H or D;

the substituent in substituted (C 1 -C 6 )alkyl, substituted (C 3 -C 6 )cycloalkyl, or, substituted (C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl is one or more selected from the group consisting of: D, halogen, hydroxyl, amino, (C 1 -C 6 )alkyl amino, (C 1 -C 6 )alkoxy, and benzyloxy; when there are a plurality of substituents, the substituents are the same or different.

14. A pharmaceutical composition comprising one or more compounds of formula I or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , and one or more pharmaceutical excipients.

15. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 6 is cyclopropyl, methyl, ethyl, hydroxymethyl, benzyloxymethyl, methoxymethyl, isobutyl, dimethylaminomethyl, isopropyl, CD 3 , or C 2 D 5 .

16. The compound of formula I, or the pharmaceutically acceptable salt, solvate, polymorph, co-crystal or stereoisomer thereof according to claim 1 , wherein,

R 3 and R 4 are independently H, methyl, ethyl, propyl, isopropyl, CD 3 , CH 2 D, CHD 2 , C 2 D 5 , CH 2 CD 3 or CHF 2 .