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

Bioorganic & Medicinal Chemistry Letters
Lilli AnselmWolfgang Haap

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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Citations

May 19, 2012·Chemical Biology & Drug Design·Steffen LindertJ Andrew McCammon
Jun 21, 2016·European Journal of Medicinal Chemistry·Nirav R PatelMange Ram Yadav
Jan 6, 2015·Chemistry : a European Journal·Alicia GalvánFélix Rodríguez
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May 4, 2017·Chemistry : a European Journal·Raffaella BucciMaria Luisa Gelmi
Jan 30, 2015·Angewandte Chemie·Elke PerschFrançois Diederich
Jan 30, 2018·Current Medicinal Chemistry·Nicolás E Núñez-NavarroFlavia C Zacconi
Nov 18, 2018·International Journal of Molecular Sciences·Majda BatoolMuhammad Asim Raza Basra
Nov 20, 2019·European Journal of Medicinal Chemistry·Haibo MeiVadim A Soloshonok
Nov 18, 2011·Journal of Chemical Information and Modeling·Bernd KuhnNeil R Taylor

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