title: Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity.
abstract: Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC(50) = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. koshio@yamanouchi.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshio
authors.forename: Fukushi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishihara
authors.forename: Yuta
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sato
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sakai-Moritani
authors.forename: Seiji
authors.initials: S
authors.lastname: Kaku
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004285:Dogs; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001372:Aza Compounds; D015842:Serine Proteinase Inhibitors