title: Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-[[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide] as a clinical candidate.
abstract: A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized.
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharma Research, Basel, Switzerland.
authors.forename: Lilli
authors.initials: L
authors.lastname: Anselm
authors.forename: David W
authors.initials: DW
authors.lastname: Banner
authors.forename: Jörg
authors.initials: J
authors.lastname: Benz
authors.forename: Katrin Groebke
authors.initials: KG
authors.lastname: Zbinden
authors.forename: Jacques
authors.initials: J
authors.lastname: Himber
authors.forename: Hans
authors.initials: H
authors.lastname: Hilpert
authors.forename: Walter
authors.initials: W
authors.lastname: Huber
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Mary
authors.forename: Michael B
authors.initials: MB
authors.lastname: Otteneder
authors.forename: Narendra
authors.initials: N
authors.lastname: Panday
authors.forename: Fabienne
authors.initials: F
authors.lastname: Ricklin
authors.forename: Martin
authors.initials: M
authors.lastname: Stahl
authors.forename: Stefan
authors.initials: S
authors.lastname: Thomi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Haap
mesh_terms: D065427:Factor Xa Inhibitors; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D065427:Factor Xa Inhibitors; D011759:Pyrrolidines