生物电子等排原理在药物先导化合物优化中的应用

The application of the bioisosterism in lead optimization

先导化合物的优化是新药研究和开发的重要环节。由于先导化合物只提供一种具有特定药理作用的新结构类型,往往由于在药理、药效学、药代动力学等方面的缺点或不足而不能直接用于临床。因此,需要对先导化合物进行进一步化学结构改造或修饰,以期优化上述特性。“生物电子等排取代(bioisostericreplacement)”即为对先导化合物进行合理优化的有效策略之一。本文简要综述了生物电子等排原理在药物先导化合物优化中的应用。

The rational optimization of lead compounds into drug candidates is very important in the process of new drug development. Because a lead compound with a desired pharmacological activity may have associated with its drawbacks of pharmacology to promise the clinical usage, it is necessary to chemically modify the compounds to exclude such drawbacks by various approaches. The bioisosteric replacement represents a successful one. We herein review the principle of bioisosterism and some examples.