(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

Moore, Blake
P.; Chung, Dong Hoon; Matharu, Daljit S.; Golden, Jennifer E.; Maddox, Clinton; Rasmussen, Lynn; Noah, James W.; Sosa, Melinda I.; Ananthan, Subramaniam; Tower, Nichole, A.; White, E. Lucile; Jia, Fuli; Prisinzano, Thomas
E.; Aubé, Jeffrey; Jonsson, Colleen
B.; Severson, William E.

doi:10.1021/jm300612z.s001

(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

journal contribution

posted on 2012-10-25, 00:00 authored by Blake P. Moore, 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

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.

(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

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