Isoindoline derivative, pharmaceutical composition and use thereof

A method of regulating generation or activity of PDE4 and/or TNF-α, or treating a disease, disorder or condition related to abnormal generation or regulation of PDE4 and/or TNF-α, wherein the disease, disorder or condition is psoriatic arthritis or plaque psoriasis, comprising

• administering to a subject in need of such treatment an effective amount of 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;
• R1 and R2 are independently H, D, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C3-C6)cycloalkyl, R6—S(O)2— or R6—C(O)—;
• R6 is substituted or unsubstituted (C3-C6)cycloalkyl;
• or (C1-C6)alkyl, which is optionally substituted with one or more groups selected from D, halogen, hydroxyl, amino, (C1-C6)alkyl amino, (C1-C6)alkoxy and benzyloxy;
• X1, X2, X3, X4, X5 and X6 are independently CH, CD, CR7 or N;
• R7 is halogen or cyano;
• R3 and R4 are independently H, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C3-C6)cycloalkyl, or, substituted or unsubstituted (C1-C6)alkyl-(C3-C6)cycloalkyl;
• R5 is substituted or unsubstituted (C1-C6)alkyl;
• R10, R11 and R12 are independently H or D;
• the substituent in substituted (C1-C6)alkyl, substituted (C3-C6)cycloalkyl, or, substituted (C1-C6)alkyl-(C3-C6)cycloalkyl is one or more selected from the group consisting of:
• D, halogen, hydroxyl, amino, (C1-C6)alkyl amino, (C1-C6)alkoxy and benzyloxy;
• when there are a plurality of substituents, the substituents are the same or different;
• provided that:
• one of X1, X2, X3, X4, X5 and X6 is N;
• wherein the disease, disorder or condition is psoriatic arthritis or plaque psoriasis.