Design and structure–activity relationships of novel inhibitors of human rhinovirus 3C protease. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Kawatkar, S.P.; Gagnon, M.; Hoesch, V.; Tiong-Yip, C.; Johnson, K.; Ek, M.; Nilsson, E.; Lister, T.; Olsson, L.; Patel, J.; Yu, Q.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3248
• Page End: 3252
• Publication Date: 2016-07-15
• Subjects: Human rhino virus -- Rupintrivir -- 3C protease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.066
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Human rhinovirus (HRV) is a primary cause of common cold and is linked to exacerbation of underlying respiratory diseases such as asthma and COPD. HRV 3C protease, which is responsible for cleavage of viral polyprotein in to proteins essential for viral life-cycle, represents an important target. We have designed proline- and azetidine-based analogues of Rupintrivir that target the P2 pocket of the binding site. Potency optimization, aided with X-ray crystallography and quantum mechanical calculations, led to compounds with activity against a broad spectrum of HRV serotypes. Altogether, these compounds represent alternative starting points to identify promising leads in our continual efforts to treat HRV infections.