Optimization and SAR research at the piperazine and phenyl rings of JNJ4796 as new anti-influenza A virus agents, part 1.

ID: ALA4825697

Journal: Eur J Med Chem

Title: Optimization and SAR research at the piperazine and phenyl rings of JNJ4796 as new anti-influenza A virus agents, part 1.

Authors: Wang A, Li Y, Lv K, Gao R, Wang A, Yan H, Qin X, Xu S, Ma C, Jiang J, Wei Z, Zhang K, Liu M.

Abstract: JNJ4796, a small molecule fuse inhibitor targeting the conserved stem region of hemagglutinin, effectively neutralized a broad spectrum of group 1 influenza A virus (IAV), and protected mice against lethal and sublethal influenza challenge after oral administration. In this study, we reported the modification and structure-activity relationship (SAR) of C (piperazine ring) and E (phenyl ring) rings of JNJ4796. Compound (R)-2c was identified to show excellent in vitro activity against IAV H1N1 and Oseltamivir-resistant IAV H1N1 stains (IC₅₀: 0.03-0.06 μM), low cytotoxicity (CC₅₀ > 200 μM), accepted oral PK profiles and low inhibition rate of hERG (13.2%, at 10 μM). Evaluation for the in vivo anti-IAV efficacy of (R)-2c will begin soon.

CiteXplore: 34126455

DOI: 10.1016/j.ejmech.2021.113591

Patent ID: ┄