title: Nonbenzamidine isoxazoline derivatives as factor Xa inhibitors.
abstract: Factor Xa (fXa) is an important serine protease in the blood coagulation cascade. Inhibition of fXa has emerged as an attractive target for potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein, we describe a series of non-benzamidine isoxazoline derivatives as fXa inhibitors. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline 1 (ST368) has a K(i) value of 1.5 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.
authors.affiliation: Bristol-Myers Squibb Co., PO Box 80500, Wilmington, DE 19880-0500, USA. mimi.quan@bms.com
authors.forename: Mimi L
authors.initials: ML
authors.lastname: Quan
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ellis
authors.forename: Ming Y
authors.initials: MY
authors.lastname: He
authors.forename: Ann Y
authors.initials: AY
authors.lastname: Liauw
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wright
authors.forename: Pancras C
authors.initials: PC
authors.lastname: Wong
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
mesh_terms: D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D011817:Rabbits
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D007202:Indicators and Reagents; D007555:Isoxazoles