| 摘要 |
PURPOSE: Provided are compounds which are inhibitors of interleukin-1ss converting enzyme. Also a method of treatment of stroke, reperfusion injury, Alzheimer's disease, shigellosis, inflammatory diseases, and a pharmaceutically acceptable composition containing the compound are provided. CONSTITUTION: Compounds which are inhibitors of interleukin-1 beta converting enzyme that have formula (I) wherein R¬1 is R¬3CO-, R¬3SO2-, each R¬a is independently hydrogen, C1-C6 alkyl, or -(CH2)n aryl; R¬2 is -(CRR)n-aryl, -(CRR)n-X-aryl, -(CRR)n-heteroaryl, -(CRR)n-X-heteroaryl, -(CRR)n-(substituted-heteroaryl), -(CRR)n-(substituted-aryl), -(CRR)n-X-(substituted-aryl), -(CRR)n-aryl-aryl, -(CRR)n-aryl-heteroaryl, -(CRR)n-aryl-(CH2)n-aryl, -(CRR)n-CH(aryl)2, -(CRR)n-cycloalkyl, -(CRR)n-X-cycloalkyl, -(CRR)n-heterocycle, -(CRR)n-X-heterocycle, -(CRR)n substituted heterocycle, each R is independently hydrogen, C1-C6 alkyl, halogen or hydroxy; X is O or S; R3 is C1 -C6 alkyl, aryl heteroaryl, -(CHR)n-aryl, -(CHR)n-heteroaryl, -(CHR)n-substituted heteroaryl, -(CHR)n-substituted aryl, -(CRR)nS(CH2)n-aryl, cycloalkyl, substituted cycloalkyl, heterocycle, substituted heterocycle, each R¬1 is independently C1-C6 alkyl, C1 -C6 alkylaryl, aryl, or hydrogen; each J is independently -C02R¬b, -CONR¬bR¬b, -SO2NR¬bR¬b, or -SO2R¬b; each R¬b is independently hydrogen, C1-C6 alkyl, aryl, substituted aryl; arylalkyl, heteroarylalkyl, substituted arylalkyl, or substituted heteroarylalkyl; R4 is hydrogen, C1-C6 alkyl, -phenyl, R6 is hydrogen, C 1 -C6 alkyl, -(CH2)n aryl, -(CH2)nCO2Ra, hydroxyl substituted C1-C6 alkyl, or imidazole substituted C1-C6 alkyl; each n is independently 0 to 3, and the pharmaceutically acceptable, salts, esters, amides, and prodrugs thereof.
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