Discovery of a novel series of CXCR3 antagonists

Stefano Crosignani; Marc Missotten; Christophe Cleva; Ruggero Dondi; Yann Ratinaud; Yves Humbert; Ashis Baran Mandal; Agnès Bombrun; Christine Power; André Chollet; Amanda Proudfoot

doi:10.1016/j.bmcl.2010.04.113

Discovery of a novel series of CXCR3 antagonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3614-7. doi: 10.1016/j.bmcl.2010.04.113. Epub 2010 Apr 28.

Authors

Stefano Crosignani¹, Marc Missotten, Christophe Cleva, Ruggero Dondi, Yann Ratinaud, Yves Humbert, Ashis Baran Mandal, Agnès Bombrun, Christine Power, André Chollet, Amanda Proudfoot

Affiliation

¹ Merck Serono SA, Geneva, Switzerland. stefano.crosignani@merckserono.net

PMID: 20483605
DOI: 10.1016/j.bmcl.2010.04.113

Abstract

The discovery of a novel series of CXCR3 antagonists is described. Starting from an HTS positive, iterative optimization gave potent compounds (IC(50) 15 nM in a chemotaxis assay). The strategy employed to improve the metabolic stability of these derivatives is described.

MeSH terms

Animals
Cell Line
Chemotaxis / drug effects*
Humans
Inhibitory Concentration 50
Mice
Microsomes
Rats
Receptors, CXCR3 / antagonists & inhibitors*
Structure-Activity Relationship
T-Lymphocytes / physiology

Substances

Receptors, CXCR3