Spirocyclic Scaffolds in Medicinal Chemistry
Spirocyclic Scaffolds in Medicinal Chemistry
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DOI：
10.1021/acs.jmedchem.0c01473
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发表时间：
2021-01-14
影响因子：
7.3
通讯作者：
Krasavin, Mikhail
中科院分区：
文献类型：
--
作者：
Hiesinger, Kerstin;Dar'in, Dmitry;Krasavin, Mikhail
螺环支架被纳入各种已批准的药物和候选药物中。人们对平面生物活性化合物的兴趣日益浓厚，从而促进了制备螺环支架的合成方法的发展。在本视角中，我们总结了获得螺环系统的多种合成路线。讨论了螺环对效力和选择性的影响，包括立体化学方面。此外，我们使用选定的研究比较螺环化合物与其非螺环对应物，检查物理化学性质以及体外和体内 ADME 的变化。总之，讨论了螺环支架在药物化学中的价值。
Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed.