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(S)-N-(2,5-二甲基苯基)-1-(8-喹啉磺酰基)吡咯烷-2-甲酰胺作为一种小分子抑制剂探针,用于研究呼吸道合胞病毒感染。

(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.

机构信息

Southern Research Specialized Biocontainment Screening Center, Southern Research Institute, Birmingham, Alabama 35205, USA.

出版信息

J Med Chem. 2012 Oct 25;55(20):8582-7. doi: 10.1021/jm300612z. Epub 2012 Oct 16.

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.

摘要

一种高通量、基于细胞的筛选方法被用于鉴定化学型作为人类呼吸道合胞病毒(hRSV)的抑制剂。对磺酰基吡咯烷骨架进行优化,得到化合物 5o,该化合物在感染的进入阶段抑制病毒诱导的细胞病变效应(EC₅₀=2.3±0.8μM),细胞毒性较小(CC₅₀=30.9±1.1μM),病毒滴度降低 100 倍。与利巴韦林相比,磺酰基吡咯烷 5o 显示出体外活性和选择性指数的提高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b47/3506029/4231eeb1be55/nihms415663f1.jpg

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