CASPASE INHIBITORS BASED ON PYRIDONE SCAFFOLD

摘要

Caspase inhibitors based on pyridone scaffold are provided to improve the selectivity to and inhibition efficiency of caspase, prevent inflammation, apoptosis, acute hepatitis or hepatic cirrhosis and rheumatoid arthritis caused by caspase, and treat diseases caused by caspase, especially liver damage caused by Fas antibody. The Caspase inhibitors based on pyridone scaffold, represented by the formula(1) or pharmaceutically acceptable salts thereof are provided, wherein R^1 is H, C1-C5 alkyl, C3-C10 cycloalkyl, aryl or side chain residue of all natural amino acids; R^2 is H, C1-C5 alkyl, C3-C10 cycloalkyl, aryl or side chain residue of all natural amino acids; R^3 is H, C1-C5 alkyl, hydroxy, C1-C5 alkoxy or halogen; R^4 is H, C1-C5 alkyl, C3-C10 cycloalkyl or aryl; R^5 is H, C1-C5 alkyl, C3-C10 cycloalkyl or aryl; R^6 is H, C1-C5 alkyl, C3-C10 cycloalkyl or aryl; R^7 and R^8 are each independently H, C1-C5 alkyl, C3-C10 cycloalkyl or aryl; and X is -CH2OR^9 in which R^9 is C1-C5 alkyl, C3-C10 cycloalkyl or aryl, -CH2OC(=O)R^10 in which R^10 is C1-C5 alkyl, C3-C10 cycloalkyl or aryl, or -CH2-W in which W is halogen.