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Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP2 Receptor Antagonist for Treatment of Asthma #MMPMID28523115
Sandham DA; Barker L; Brown L; Brown Z; Budd D; Charlton SJ; Chatterjee D; Cox B; Dubois G; Duggan N; Hall E; Hatto J; Maas J; Manini J; Profit R; Riddy D; Ritchie C; Sohal B; Shaw D; Stringer R; Sykes DA; Thomas M; Turner KL; Watson SJ; West R; Willard E; Williams G; Willis J
ACS Med Chem Lett 2017[May]; 8 (5): 582-6 PMID28523115show ga
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)-1H-pyrrolo[2,3-b]pyr idin-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.