效力
衣壳
鼻病毒
立体化学
广谱
化学
戒指(化学)
体外
结构-活动关系
铅化合物
病毒
病毒学
生物
生物化学
组合化学
有机化学
作者
Martina Richter,Maria G. Khrenova,Elena Kazakova,Olga Riabova,Anna Egorova,Vadim Makarov,Michaela Schmidtke
标识
DOI:10.1016/j.antiviral.2024.105993
摘要
Pyrazolo[3,4-d]pyrimidines represent one potent class of well tolerated and highly active rhinovirus (RV) inhibitors that act as capsid binders. The lead compound OBR-5-340 inhibits a broad-spectrum of RVs. Aiming to improve lead activity, we evaluated the impact of structural modifications in the 3-phenyl ring of OBR-5-340 on its potency and spectrum of anti-RV activity vitro. Our results demonstrate the crucial role of substitution at position 4 for strong, broad-spectrum anti-RV activity. The 4-methyl (RCB23137) and 4-chloro (RCB23138) derivatives outperformed OBR-5-340 in terms of potency and anti-RV activity spectrum. Based on these findings, the compounds were selected for computational binding studies. Molecular dynamic simulations with six RVs differing in OBR-5-340, RCB23137, and RCB23138 sensitivity proved the impact of dynamic features of two VP1 loops enveloping these inhibitors on antiviral potency.
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