Peptidic ketones as interleukin-1.beta.-converting enzyme inhibitors
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United States of America Patent
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Dec 17, 1996
Issued Date -
N/A
app pub date -
May 12, 1995
filing date -
May 7, 1993
priority date (Note) -
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Abstract
Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is (CR.sub.5 R.sub.6).sub.n, (CR.sub.5 R.sub.6).sub.n,-aryl, (CR.sub.5 R.sub.6).sub.n -heteroaryl, X-(CR.sub.5 R.sub.6).sub.n, X-(CR.sub.5 R.sub.6).sub.n -aryl or X-(CR.sub.5 R.sub.6).sub.n -heteroaryl wherein aryl and heteroaryl may be optionally substituted; X is 0 or NR.sub.5 ; R.sub.5 and R.sub.6 are independently H or lower alkyl; R.sub.2 is H, halo, lower alkyl or (CR.sub.5 R.sub.6).sub.n -aryl; R.sub.3 and R.sub.4 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 CH.sub.2 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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