(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

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

Research output: Research - peer-reviewArticle

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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.

LanguageEnglish (US)
Pages8582-8587
Number of pages6
JournalJournal of Medicinal Chemistry
Volume55
Issue number20
DOIs
StatePublished - Oct 25 2012
Externally publishedYes

Fingerprint

Human respiratory syncytial virus
Respiratory Syncytial Virus Infections
Ribavirin
Viruses
Infection
N-(2,5-dimethylphenyl)-1-(quinolin-8-ylsulfonyl)pyrrolidine-2-carboxamide
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

(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.

In: Journal of Medicinal Chemistry, Vol. 55, No. 20, 25.10.2012, p. 8582-8587.

Research output: Research - peer-reviewArticle

Moore, BP, Chung, DH, Matharu, DS, Golden, JE, Maddox, C, Rasmussen, L, Noah, JW, Sosa, MI, Ananthan, S, Tower, NA, White, EL, Jia, F, Prisinzano, TE, Aubé, J, Jonsson, CB & Severson, WE 2012, '(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 of Medicinal Chemistry, vol 55, no. 20, pp. 8582-8587. DOI: 10.1021/jm300612z
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./ (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. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 20. pp. 8582-8587
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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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AU - Chung,Dong Hoon

AU - Matharu,Daljit S.

AU - Golden,Jennifer E.

AU - Maddox,Clinton

AU - Rasmussen,Lynn

AU - Noah,James W.

AU - Sosa,Melinda I.

AU - Ananthan,Subramaniam

AU - Tower,Nichole A.

AU - White,E. Lucile

AU - Jia,Fuli

AU - Prisinzano,Thomas E.

AU - Aubé,Jeffrey

AU - Jonsson,Colleen B.

AU - Severson,William E.

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