(S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a small molecule inhibitor probe for the study of respiratory syncytial virus infection

  • J Med Chem. 2012 Oct 25;55(20):8582-7. doi: 10.1021/jm300612z.
Blake P Moore  1 ,  Dong Hoon Chung ,  Daljit S Matharu ,  Jennifer E Golden ,  Clinton Maddox ,  Lynn Rasmussen ,  James W Noah ,  Melinda I Sosa ,  Subramaniam Ananthan ,  Nichole A Tower ,  E Lucile White ,  Fuli Jia ,  Thomas E Prisinzano ,  Jeffrey Aubé ,  Colleen B Jonsson ,  William E Severson
Affiliations
  • 1. Southern Research Specialized Biocontainment Screening Center, Southern Research Institute, Birmingham, Alabama 35205, USA.
PMID: 23043370 DOI: 10.1021/jm300612z
Abstract

A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of Infection (EC₅₀ = 2.3 ± 0.8 μM) with marginal cytotoxicity (CC₅₀ = 30.9 ± 1.1 μM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index.