Peptidic ketones as interleukin-1 beta-converting enzyme inhibitors

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作者
Sterling Winthrop Inc, King of Prussia, United States [1 ]
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Biotechnol Adv | / 3-4卷 / 756期
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Amino acids - Catalyst activity - Cells - Drug products - Enzyme inhibition - Molecular structure;
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摘要
Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein R1 is (CR5R6)n, (CR5R6)n,-aryl, (CR5R6)n-heteroaryl, X-(CR5R6)n, X-(CR5R6)n-aryl or X-(CR5R6)n-heteroaryl wherein aryl and heteroaryl may be optionally substituted; X is 0 or NR5; R5 and R6 are independently H or lower alkyl; R2 is H, halo, lower alkyl or (CR5R6)n-aryl; R3 and R4 are independently H or alkyl; A is a D or L isomer of an amino acid selected from the group consisting of alanine, valine, leucine, isoleucine, proline, phenylalanine, glycine, tyrosine, methionine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, histidine and beta-thienylalanine; Z is CH2 or O; and n is 0-4; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1 beta protease activity in a mammal utilizing the compounds and compositions.
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