title: Amido-(propyl and allyl)-hydroxybenzamidines: development of achiral inhibitors of factor Xa.
abstract: The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidine coagulation factor Xa inhibitors is described. These achiral inhibitors are selective for fXa vis a vis structurally related serine proteases and are readily prepared in 6-7 linear steps. The most potent member 9j (fXa Ki = 0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mammalian plasma.
authors.affiliation: Department of Medicinal Chemistry, Rhone-Poulenc Rorer, Collegeville, PA 19426-0107, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: H W
authors.initials: HW
authors.lastname: Pauls
authors.forename: A P
authors.initials: AP
authors.lastname: Spada
authors.forename: M
authors.initials: M
authors.lastname: Czekaj
authors.forename: G
authors.initials: G
authors.lastname: Liang
authors.forename: V
authors.initials: V
authors.lastname: Chu
authors.forename: D J
authors.initials: DJ
authors.lastname: Colussi
authors.forename: K D
authors.initials: KD
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D001550:Benzamidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D008958:Models, Molecular; D015394:Molecular Structure; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001550:Benzamidines; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors