Document Detail


(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.
MedLine Citation:
PMID:  23043370     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-16
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  55     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-25     Completed Date:  2013-02-05     Revised Date:  2013-10-30    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8582-7     Citation Subset:  IM    
Affiliation:
Southern Research Specialized Biocontainment Screening Center, Southern Research Institute, Birmingham, Alabama 35205, USA.
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MeSH Terms
Descriptor/Qualifier:
Antiviral Agents / chemical synthesis*,  chemistry,  pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Cytopathogenic Effect, Viral / drug effects
High-Throughput Screening Assays
Humans
Pyrrolidines / chemical synthesis*,  chemistry,  pharmacology
Quinolines / chemical synthesis*,  chemistry,  pharmacology
Respiratory Syncytial Viruses / drug effects*,  physiology
Ribavirin / pharmacology
Stereoisomerism
Structure-Activity Relationship
Sulfonamides / chemical synthesis*,  chemistry,  pharmacology
Sulfones / chemical synthesis*,  chemistry,  pharmacology
Viral Load / drug effects
Virus Internalization / drug effects
Virus Replication / drug effects
Grant Support
ID/Acronym/Agency:
1 R03 MH082403-01A1/MH/NIMH NIH HHS; R03 MH082403/MH/NIMH NIH HHS; U54 HG005031/HG/NHGRI NIH HHS; U54 HG005034/HG/NHGRI NIH HHS; U54 HG005034-01/HG/NHGRI NIH HHS; U54HG005031/HG/NHGRI NIH HHS
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/N-(2,5-dimethylphenyl)-1-(quinolin-8-ylsulfonyl)pyrrolidine-2-carboxamide; 0/Pyrrolidines; 0/Quinolines; 0/Sulfonamides; 0/Sulfones; 36791-04-5/Ribavirin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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