title: Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors.
abstract: 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.
authors.affiliation: 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
authors.forename: Taisaku
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruoka
authors.forename: Seiichi
authors.initials: S
authors.lastname: Imajo
authors.forename: Harukazu
authors.initials: H
authors.lastname: Fukami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomimori
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakatsuka
mesh_terms: 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
chemical_list: D001381:Azepines; D015842:Serine Proteinase Inhibitors; D053818:Chymases