Peptidyl human heart chymase inhibitors. 1. Synthesis and inhibitory activity of difluoromethylene ketone derivatives bearing P' binding subsites.
Peptidyl difluoromethylene ketone derivatives were designed to take advantage of probable additional interactions with the S' subsite of human heart chymase. They showed potent inhibitory activities against human heart chymase and were more efficient than bovine chymotrypsin.
Eda
M
M
Department of Medicinal Chemistry, Green Cross Research Laboratories, Osaka, Japan.
Ashimori
A
A
Akahoshi
F
F
Yoshimura
T
T
Inoue
Y
Y
Fukaya
C
C
Nakajima
M
M
Fukuyama
H
H
Imada
T
T
Takai
S
S
Shiota
N
N
Miyazaki
M
M
Nakamura
N
N
D000818:Animals; D002417:Cattle; D053818:Chymases; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004151:Dipeptides; D007202:Indicators and Reagents; D007659:Ketones; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D053818:Chymases