.alpha.-(1,3-dicarbonylenol ether) methyl ketones as cysteine protease inhibitors
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United States of America Patent
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Feb 3, 1998
Grant Date -
N/A
app pub date -
Jun 7, 1995
filing date -
Dec 8, 1993
priority date (Note) -
Expired
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Abstract
Cysteine protease inhibitors which deactivate the protease by covalently bonding to the cysteine protease and releasing the enolate of a 1,3-dicarbonyl (or its enolic form). The cysteine protease inhibitors of the present invention accordingly comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a .beta.-dicarbonyl enol ether leaving group.
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