Peptidic ketones as interleukin-1 beta-converting enzyme inhibitors

Roland E. Dolle, Todd L. Graybill, Gary Speier, Catherine P. Prouty, Stanley J. Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Number of pages1
JournalBiotechnology Advances
Volume15
Issue number3-4
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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