(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

doi:10.1021/jm300612z

(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: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	8582-8587
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	20
DOIs	https://doi.org/10.1021/jm300612z
State	Published - Oct 25 2012

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm300612z

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Moore, B. P., Chung, D. H., Matharu, D. S., Golden, J. E., Maddox, C., Rasmussen, L., Noah, J. W., Sosa, M. I., Ananthan, S., Tower, N. A., White, E. L., Jia, F., Prisinzano, T. E., Aubé, J., Jonsson, C. B., & Severson, W. E. (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, 55(20), 8582-8587. https://doi.org/10.1021/jm300612z

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title = "(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",

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.",

author = "Moore, {Blake P.} and Chung, {Dong Hoon} and Matharu, {Daljit S.} and Golden, {Jennifer E.} and Clinton Maddox and Lynn Rasmussen and Noah, {James W.} and Sosa, {Melinda I.} and Subramaniam Ananthan and Tower, {Nichole A.} and White, {E. Lucile} and Fuli Jia and Prisinzano, {Thomas E.} and Jeffrey Aub{\'e} and Jonsson, {Colleen B.} and Severson, {William E.}",

year = "2012",

month = oct,

day = "25",

doi = "10.1021/jm300612z",

language = "English",

volume = "55",

pages = "8582--8587",

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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. https://doi.org/10.1021/jm300612z

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

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - (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

AU - Moore, Blake P.

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.

PY - 2012/10/25

Y1 - 2012/10/25

N2 - 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.

AB - 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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(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

Abstract

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