title: Anthranilamide-based N,N-dialkylbenzamidines as potent and orally bioavailable factor Xa inhibitors: P4 SAR.
abstract: Anthranilamide-based benzamidine compound 4 and its N-substituted analogs were designed and examined as factor Xa inhibitors using substituted benzamidines as unconventional S4 binding element. A group of N,N-dialkylbenzamidines (11, 17 and 24) have been discovered as potent factor Xa inhibitors with strong anticoagulant activity and promising oral PK profiles.
authors.affiliation: Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA.
authors.forename: Penglie
authors.initials: P
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Bao
authors.forename: Jingmei
authors.initials: J
authors.lastname: Fan
authors.forename: Zhaozhong J
authors.initials: ZJ
authors.lastname: Jia
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wong
authors.forename: Gary
authors.initials: G
authors.lastname: Park
authors.forename: Athiwat
authors.initials: A
authors.lastname: Hutchaleelaha
authors.forename: Robert M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: Bing-Yan
authors.initials: BY
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001550:Benzamidines / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001682:Biological Availability; D004285:Dogs; D015951:Factor Xa / Q000493:pharmacokinetics; D065427:Factor Xa Inhibitors; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D001550:Benzamidines; D065427:Factor Xa Inhibitors; D062367:ortho-Aminobenzoates; D015951:Factor Xa; C000219:anthranilamide