6-Acylamino-2-[(alkylsulfonyl)oxy]-1H-isoindole-1,3-dione mechanism-based inhibitors of human leukocyte elastase.
A study of various 2-[(alkylsulfonyl)oxy]-6-substituted-1H-isoindole-1,3-diones' inhibition of chymotrypsin compared to inhibition of HLE reveals that acylamino substitution in the 6-position increases selectivity and potency of these inhibitors for HLE. The best HLE inhibitor in this series was 6-(methylglutaryl)amino-2-[(ethylsulfonyl)oxy]-1H-isoindole-1,3-di one with a kobs/[I] = 220,000 M(-1) s(-1).
Kerrigan
J E
JE
Department of Chemistry, University of South Alabama, Mobile 36688, USA.
Walters
M C
MC
Forrester
K J
KJ
Crowder
J B
JB
Christopher
L J
LJ
D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015843:Serpins; D013329:Structure-Activity Relationship
D007211:Indoles; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C075177:SERPINB1 protein, human; D002918:Chymotrypsin; D019272:Leukocyte Elastase