Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones.
The present work demonstrates that the 1,3-diazetidine-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha-chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase.
Aoyama
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, 553-0002, Osaka, Japan. yasunori.aoyama@shionogi.co.jp
Uenaka
M
M
Konoike
T
T
Hayasaki-Kajiwara
Y
Y
Naya
N
N
Nakajima
M
M
D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology*; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity
D001384:Azetidines; D015842:Serine Proteinase Inhibitors; D002403:Cathepsins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase