title: Discovery of novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as human chymase inhibitors using structure-based drug design.
abstract: A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones were explored as human chymase inhibitors using structure-based drug design according to the X-ray cocrystal structure of chymase and compound 1. The optimization focused on the prime site led to the attainment of compounds that showed potent inhibitory activity, and among them, 18R shows a novel interaction mode.
authors.affiliation: Asubio Pharma Co., Ltd, 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. tanaka.taisaku.fu@asubio.co.jp
authors.forename: Taisaku
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hajime
authors.initials: H
authors.lastname: Sugawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruoka
authors.forename: Seiichi
authors.initials: S
authors.lastname: Imajo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muto
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D053818:Chymases / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005036:Ethylmorphine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C545228:1,4-diazepane; C538783:6-(5-chloro-2-methoxybenzyl)-4-alarkylaminocarbonyl-1,4-diazepane-2,5-dione; D001381:Azepines; D004791:Enzyme Inhibitors; D053818:Chymases; D005036:Ethylmorphine