1. Discovery of a novel series of CXCR3 antagonists
- Author
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Agnes Bombrun, Ashis Baran Mandal, Amanda E. I. Proudfoot, André Chollet, Ruggero Dondi, Stefano Crosignani, Christophe Cleva, Marc Missotten, Yann Ratinaud, Yves Humbert, and Christine A. Power
- Subjects
Receptors, CXCR3 ,Series (mathematics) ,Chemistry ,Stereochemistry ,Chemotaxis ,T-Lymphocytes ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Computational biology ,Metabolic stability ,Biochemistry ,Cell Line ,Rats ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Microsomes ,Drug Discovery ,Molecular Medicine ,Animals ,Humans ,Molecular Biology ,Chemotaxis assay - Abstract
The discovery of a novel series of CXCR3 antagonists is described. Starting from an HTS positive, iterative optimization gave potent compounds (IC50 15 nM in a chemotaxis assay). The strategy employed to improve the metabolic stability of these derivatives is described.
- Published
- 2010