(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

摘要

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 (EC_(50) = 2.3 ± 0.8 μM) with marginal cytotoxicity (CC_(50) = 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.