有机含氟药物与靶标蛋白质的复杂分子间相互作用

Complicated intermolecular interactions formed between organofluorine and drug target

有机含氟化合物在目前上市药物中占到20%~25%,在药物化学中发挥了重要作用。在有机化合物中引入氟是药物化学家们改变小分子的物理化学性质的常用策略,更重要的是氟代还会改变小分子与蛋白质的结合亲和力,从而影响化合物的活性及成药性。从分子层面上看,有机氟中的F原子可以与靶标蛋白形成多种分子间弱相互作用,例如氢键、卤键、C-F…π作用、极性作用等。由于氟自身的特殊性,这些作用有其独特的特点,或表现在作用的几何结构上,或表现在作用的强度及本质上等,相关研究也成为了关注的焦点。为了促进有机氟在药物化学中更好的应用,本文概述了相关的研究进展,对有机氟所形成的氢键、卤键、C-F…π作用、极性作用等的研究进行了综述。

Fluorinated compounds, which now make up 20%-25% of all marketed chemical drugs, are playing significant role and showing great potential in medicinal chemistry. Fluorine substitution is always utilized to change the physicochemical properties of the compounds to improve the ADME/T properties. In addition, fluorine substitution leads to improvement of the ligand binding affinity. With respect to molecular level, organofluorine can form various intermolecular interactions with the target proteins, e.g., hydrogen bond, halogen bond, C-F…π interaction, polar interaction and so on. These interactions display unique properties or nature due to the specificity of fluorine atom, which are at the center of attention. This paper reviews the related research background, followed by the research progress of hydrogen bond, halogen bond, C-F…πinteraction, polar interaction and some other interactions involved organofluorine.