title: Optimization of the beta-aminoester class of factor Xa inhibitors. Part 2: Identification of FXV673 as a potent and selective inhibitor with excellent In vivo anticoagulant activity.
abstract: Further optimization of the beta-aminoester class of factor Xa (fXa) inhibitors is described culminating in the identification of 9c (FXV673), a potent and selective factor Xa inhibitor with excellent in vivo anticoagulant activity. An X-ray structure of FXV673 bound to human fXa is also presented. Based on its selectivity, potent in vivo activity and favorable pre-clinical safety profile, FXV673 was selected for further development and is currently undergoing clinical trials.
authors.affiliation: Drug Innovation and Approval, Aventis Pharmaceuticals, Route 202-206, Bridgewater, NJ 08807, USA. kevin.guertin@roche.com
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Guertin
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Gardner
authors.forename: Scott I
authors.initials: SI
authors.lastname: Klein
authors.forename: Allison L
authors.initials: AL
authors.lastname: Zulli
authors.forename: Mark
authors.initials: M
authors.lastname: Czekaj
authors.forename: Yong
authors.initials: Y
authors.lastname: Gong
authors.forename: Alfred P
authors.initials: AP
authors.lastname: Spada
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maignan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guilloteau
authors.forename: Karen D
authors.initials: KD
authors.lastname: Brown
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Colussi
authors.forename: Valeria
authors.initials: V
authors.lastname: Chu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Heran
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Morgan
authors.forename: Ross G
authors.initials: RG
authors.lastname: Bentley
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Dunwiddie
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Leadley
authors.forename: Henry W
authors.initials: HW
authors.lastname: Pauls
mesh_terms: D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003497:Cyclic N-Oxides / Q000737:chemistry* / Q000494:pharmacology*; D004952:Esters; D065427:Factor Xa Inhibitors; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D003497:Cyclic N-Oxides; D004952:Esters; D065427:Factor Xa Inhibitors; D011725:Pyridines; D015842:Serine Proteinase Inhibitors; C435830:otamixaban