title: Design, synthesis and pharmacological evaluation of 3-benzylazetidine-2-one-based human chymase inhibitors.
abstract: 3-Benzylazetidine-2-one derivatives were designed and evaluated as a novel series of chymase inhibitors. Structure-activity relationship studies of 3-benzylazetidine-2-ones led to compounds 23, which exhibited 3.1 nM inhibition of human chymase and enhancement of stability in human plasma (t(1/2) 6h).
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, 553-0002, Osaka, Japan. yasunori.aoyama@shionogi.co.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Aoyama
authors.forename: M
authors.initials: M
authors.lastname: Uenaka
authors.forename: M
authors.initials: M
authors.lastname: Kii
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Konoike
authors.forename: Y
authors.initials: Y
authors.lastname: Hayasaki-Kajiwara
authors.forename: N
authors.initials: N
authors.lastname: Naya
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
mesh_terms: D001384:Azetidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001769:Blood / Q000378:metabolism; D053818:Chymases; D015195:Drug Design; D006801:Humans; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C116379:2-azetidinone; C449181:3-benzylazetidin-2-one; D001384:Azetidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases