Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP 2 Receptor Antagonist for Treatment of Asthma.

David A Sandham, Lucy Barker, Lyndon Brown, Zarin Brown, David Budd, Steven J Charlton, Devnandan Chatterjee, Brian Cox, Gerald Dubois, Nicholas Duggan, Edward Hall, Julia Hatto, Janet Maas, Jodie Manini, Rachael Profit, Darren Riddy, Catherine Ritchie, Bindi Sohal, Duncan Shaw, Rowan Stringer, David A Sykes, Matthew Thomas, Katharine L Turner, Simon J Watson, Ryan West, Elisabeth Willard, Gareth Williams, Jennifer Willis

ACS Medicinal Chemistry Letters 2017 May 12

Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl)acetic acid (compound 11 , NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.

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