| 摘要 |
Caspase inhibitors based on pyridazinone scaffold are provided to improve inhibition efficiency and selectivity to caspase and control inflammation and apoptosis caused by caspase, so that the caspase inhibitors are useful for prevention and treatment of diseases caused by caspase including dementia, cerebral apoplexy, brain damage by AIDS(acquired immuno-deficiency syndrome) or hepatitis virus, diabetes, gastric ulcer, liver disease, chronic hepatitis, graft rejection, rheumatoid arthritis, ischemic heart disease and liver cirrhosis. Caspase inhibitors based on pyridazinone scaffold are represented by the formula(1), 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, hydroxyl, C4-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 and R^7 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, -CH2-OP(=O)R^11 in which R^11 is C1-C5 alkyl, C3-C10 cycloalkyl or aryl, or -CH2-W in which W is halogen.
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