Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors.
A novel series of 6-substituted 4-sulfonyl-1,4-diazepane-2,5-diones were designed, synthesized and evaluated as human chymase inhibitors. Structure-activity relationship studies led to the identification of a potent inhibitor, (6S)-6-(5-chloro-2-methoxybenzyl)-4-[(4-chlorophenyl)sulfonyl]-1,4-diazepane-2,5-dione, with an IC(50) of 0.027 microM.
Tanaka
Taisaku
T
Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd, 1-1-1 Wakayamadai Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan. tanaka.taisasku.fu@asubio.co.jp
Muto
Tsuyoshi
T
Maruoka
Hiroshi
H
Imajo
Seiichi
S
Fukami
Harukazu
H
Tomimori
Yoshiaki
Y
Fukuda
Yoshiaki
Y
Nakatsuka
Takashi
T
D001381:Azepines / Q000138:chemical synthesis / Q000494:pharmacology*; D053818:Chymases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001381:Azepines; D015842:Serine Proteinase Inhibitors; D053818:Chymases