2. Academic Validation
  3. (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

(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

Affiliation

  • 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.

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