Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma

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

Abstract

Further optimization of an initial DP2 receptor antagonist clinical candidate NVPQAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2- (trifluoromethyl)benzyl)-1H-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.

Citation

Sandham, D. A., Barker, L., Brown, L., Brown, Z., Budd, D., Charlton, S. J., 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., …Willis, J. (2017). Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma. ACS Medicinal Chemistry Letters, 8(5), 582-586. https://doi.org/10.1021/acsmedchemlett.7b00157

• Journal Article Type: Article
• Acceptance Date: Apr 25, 2017
• Online Publication Date: Apr 27, 2017
• Publication Date: May 11, 2017
• Deposit Date: Jul 12, 2017
• Journal: ACS Medicinal Chemistry Letters
• Electronic ISSN: 1948-5875
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 5
• Pages: 582-586
• DOI: https://doi.org/10.1021/acsmedchemlett.7b00157
• Keywords: DP2 receptor antagonist, severe asthma, clinical candidate
• Public URL: https://nottingham-repository.worktribe.com/output/857565
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.7b00157
• Contract Date: Jul 11, 2017