Department of Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK.
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6031-5. doi: 10.1016/j.bmcl.2011.08.083. Epub 2011 Aug 24.
To try and generate broad spectrum human rhinovirus VP1 inhibitors with more attractive physicochemical, DMPK and safety profiles, we explored the current SAR of known VP1 compounds. This lead to the identification of specific structural regions where reduction in polarity can be achieved, so guiding chemistry to analogues with significantly superior profiles to previously reported inhibitors.
为了尝试生成具有更具吸引力的物理化学、药物代谢动力学和安全性特征的广谱人鼻病毒 VP1 抑制剂,我们探索了已知 VP1 化合物的当前 SAR。这导致确定了可以实现极性降低的特定结构区域,从而指导化学合成具有明显优于先前报道的抑制剂的类似物。