2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2010 Sep 1;20(17):5313-9. doi: 10.1016/j.bmcl.2010.06.126.
Lilli Anselm 1,  David W Banner,  Jörg Benz,  Katrin Groebke Zbinden,  Jacques Himber,  Hans Hilpert,  Walter Huber,  Bernd Kuhn,  Jean-Luc Mary,  Michael B Otteneder,  Narendra Panday,  Fabienne Ricklin,  Martin Stahl,  Stefan Thomi,  Wolfgang Haap
Affiliations

Affiliation

  • 1 F. Hoffmann-La Roche Ltd, Pharma Research, Basel, Switzerland.
PMID: 20650636 DOI: 10.1016/j.bmcl.2010.06.126
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.

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