2. Academic Validation
  3. N-[6-(4-butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a novel intravenous and oral, reversible, and directly acting P2Y12 antagonist

N-[6-(4-butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a novel intravenous and oral, reversible, and directly acting P2Y12 antagonist

  • J Med Chem. 2014 Sep 11;57(17):7293-316. doi: 10.1021/jm500588w.
Christophe Boldron 1,  Angélina Besse,  Marie-Françoise Bordes,  Stéphanie Tissandié,  Xavier Yvon,  Benjamin Gau,  Alain Badorc,  Tristan Rousseaux,  Guillaume Barré,  Jérôme Meneyrol,  Gernot Zech,  Marc Nazare,  Valérie Fossey,  Anne-Marie Pflieger,  Sandrine Bonnet-Lignon,  Laurence Millet,  Christophe Briot,  Frédérique Dol,  Jean-Pascal Hérault,  Pierre Savi,  Gilbert Lassalle,  Nathalie Delesque,  Jean-Marc Herbert,  Françoise Bono
Affiliations

Affiliation

  • 1 Sanofi R&D , 195 Route d'Espagne, 31036 Toulouse Cedex, France.
PMID: 25075638 DOI: 10.1021/jm500588w
Abstract

In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 Receptor Antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from Other antiplatelet agents.

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