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. Epub 2010 Jul 1.

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.

MeSH terms

  • Factor Xa Inhibitors*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*

Substances

  • Factor Xa Inhibitors
  • Pyrrolidines