Fujii Shinya, Hashimoto Yuichi
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Future Med Chem. 2017 Apr;9(5):485-505. doi: 10.4155/fmc-2016-0193. Epub 2017 Mar 31.
Application of silyl functionalities is one of the most promising strategies among various 'elements chemistry' approaches for the development of novel and distinctive drug candidates. Replacement of one or more carbon atoms of various biologically active compounds with silicon (so-called sila-substitution) has been intensively studied for decades, and is often effective for alteration of activity profile and improvement of metabolic profile. In addition to simple C/Si exchange, several novel approaches for utilizing silicon in medicinal chemistry have been suggested in recent years, focusing on the intrinsic differences between silicon and carbon. Sila-substitution offers great potential for enlarging the chemical space of medicinal chemistry, and provides many options for structural development of drug candidates.
在各种用于开发新型独特候选药物的“元素化学”方法中，硅官能团的应用是最具前景的策略之一。几十年来，人们对各种生物活性化合物中的一个或多个碳原子用硅取代（所谓的硅取代）进行了深入研究，这通常对改变活性特征和改善代谢特征有效。除了简单的碳/硅交换外，近年来还提出了几种在药物化学中利用硅的新方法，重点关注硅和碳之间的内在差异。硅取代为扩大药物化学的化学空间提供了巨大潜力，并为候选药物的结构开发提供了许多选择。
