title: Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.
abstract: Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.
authors.affiliation: Department of Medicinal Chemistry, Rhône-Poulenc Rorer, Collegeville, PA 19426, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Becker
authors.forename: W R
authors.initials: WR
authors.lastname: Ewing
authors.forename: R S
authors.initials: RS
authors.lastname: Davis
authors.forename: H W
authors.initials: HW
authors.lastname: Pauls
authors.forename: C
authors.initials: C
authors.lastname: Ly
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: H J
authors.initials: HJ
authors.lastname: Mason
authors.forename: Y M
authors.initials: YM
authors.lastname: Choi-Sledeski
authors.forename: A P
authors.initials: AP
authors.lastname: Spada
authors.forename: V
authors.initials: V
authors.lastname: Chu
authors.forename: K D
authors.initials: KD
authors.lastname: Brown
authors.forename: D J
authors.initials: DJ
authors.lastname: Colussi
authors.forename: R J
authors.initials: RJ
authors.lastname: Leadley
authors.forename: R
authors.initials: R
authors.lastname: Bentley
authors.forename: J
authors.initials: J
authors.lastname: Bostwick
authors.forename: C
authors.initials: C
authors.lastname: Kasiewski
authors.forename: S
authors.initials: S
authors.lastname: Morgan
mesh_terms: D000818:Animals; D004285:Dogs; D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D065427:Factor Xa Inhibitors; D011760:Pyrrolidinones