title: Design and synthesis of aminophenol-based factor Xa inhibitors.
abstract: A novel potent and selective aminophenol scaffold for fXa inhibitors was developed from a previously reported benzimidazole-based naphthylamidine template. The aminophenol template is more synthetically accessible than the benzimidazole template, which simplified the introduction of carboxylic acid groups. Substitution of a propenyl-para-hydroxy-benzamidine group on the aminophenol template produced selective, sub-nanomolar fXa inhibitors. The potency of the inhibitors is partially explained with the aid of a trypsin complex crystal structure.
authors.affiliation: Discovery Research, Berlex Biosciences, 15049 San Pablo Avenue, PO Box 4099, 94804-0099, Richmond, CA, USA
authors.forename: Shung
authors.initials: S
authors.lastname: Wu
authors.forename: William J
authors.initials: WJ
authors.lastname: Guilford
authors.forename: Yuo-Ling
authors.initials: YL
authors.lastname: Chou
authors.forename: Brian D
authors.initials: BD
authors.lastname: Griedel
authors.forename: Amy
authors.initials: A
authors.lastname: Liang
authors.forename: Steve
authors.initials: S
authors.lastname: Sakata
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Shaw
authors.forename: Lan
authors.initials: L
authors.lastname: Trinh
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Zuchun
authors.initials: Z
authors.lastname: Zhao
authors.forename: Michael M
authors.initials: MM
authors.lastname: Morrissey
mesh_terms: D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry*; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000627:Aminophenols; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors