Synthesis and structure-activity relationships of a new class of 1-oxacephem-based human chymase inhibitors.
1-Oxacephem derivatives were synthesized and evaluated as a novel series of chymase inhibitors. Structure-activity relationship studies of 1-oxacephems led to compound 34, which exhibited 6 nM inhibition of human chymase and high selectivity for human chymase compared to other serine enzymes.
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 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053818:Chymases; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases