title: Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.
abstract: Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.
authors.affiliation: Discovery Research, Berlex Biosciences, Richmond, CA 94804-0099, USA. Spring_Zhao@berlex.com
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.forename: D O
authors.initials: DO
authors.lastname: Arnaiz
authors.forename: B
authors.initials: B
authors.lastname: Griedel
authors.forename: S
authors.initials: S
authors.lastname: Sakata
authors.forename: J L
authors.initials: JL
authors.lastname: Dallas
authors.forename: M
authors.initials: M
authors.lastname: Whitlow
authors.forename: L
authors.initials: L
authors.lastname: Trinh
authors.forename: J
authors.initials: J
authors.lastname: Post
authors.forename: A
authors.initials: A
authors.lastname: Liang
authors.forename: M M
authors.initials: MM
authors.lastname: Morrissey
authors.forename: K J
authors.initials: KJ
authors.lastname: Shaw
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D065427:Factor Xa Inhibitors; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D014361:Trypsin Inhibitors; D013917:Thrombin