Selective inhibition of MALT1 protease by phenothiazine derivatives

摘要

The invention relates to a compound for use in treating a cancer, wherein the cancer depends on the proteolytic activity of the MALT1 protease, and wherein the compound has the general formula (I);;wherein X is N or C; Y is S, O, SO2, SO, NH, CO, CH2, CH═CH, CH2═CH2; ( )z is a C1-C5 linear or branched alkyl chain; A is NR3R4, or OR5, or HET; R1 and R2 in each occurrence are independently selected from —H, —CH3, —OH, —OCH3, —SCH3, —F, —Cl, —CF3, —NH2, and —COOH; R3, R4, and R5 are H, or C1-C5 linear or branched alkyl groups, and HET is a heterocyclic ring of 5, 6, or 7 members, wherein the ring atoms can be C, O, N, or S, the ring can be saturated or aromatic, and the ring can be substituted with H or C1-C5 linear or branched alkyl groups; or a pharmaceutically acceptable salt, prodrug, enantiomer, diastereomer, racemic mixture, crystalline form, amorphous form, unsolvated form or solvate of said compound. The compound of the invention may further be used in the treatment of MALT1-dependent immune diseases.

主权项

1. A method for treating a disease that depends on the activity of the MALT1 protease in a subject, comprising administering an effective amount of a compound having the formula (I) wherein X is N or C; Y is S, O, SO2, SO, NH, CO, CH2, CH═CH, or CH2—CH2; ( )z is a C1-C5 linear or branched alkyl chain; A is NR3R4, or OR5, or HET R1 and R2 in each occurrence are independently selected from —H, —CH3, —OH, —OCH3, —SCH3, —F, —Cl, —CF3, —NH2, and —COOH; R3, R4, and R5 are H, or C1-C5 linear or branched alkyl groups, and HET is a heterocyclic ring of 5, 6, or 7 members, wherein the ring atoms can be C, O, N, or S, the ring can be saturated or aromatic, and the ring can be substituted with H or C1-C5 linear or branched alkyl groups; or a pharmaceutically acceptable salt, prodrug, enantiomer, diastereomer, racemic mixture, crystalline form, amorphous form, unsolvated form or solvate of said compound.