1-Oxacephem-based human chymase inhibitors: discovery of stable inhibitors in human plasma.
1-Oxacephem derivatives were evaluated as a novel series of chymase inhibitors. The structure-activity relationship studies of 1-oxacephems led to compounds 15, which exhibited 27 nM inhibition of human chymase and improvement of stability in human plasma (t 1/2 1.5 h).
Aoyama
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan. yasunori.aoyama@shionogi.co.jp
Uenaka
M
M
Konoike
T
T
Iso
Y
Y
Nishitani
Y
Y
Kanda
A
A
Naya
N
N
Nakajima
M
M
D002511:Cephalosporins / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053818:Chymases; D004795:Enzyme Stability; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010949:Plasma / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases