Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Italy.
Curr Med Chem. 2012;19(28):4794-815. doi: 10.2174/092986712803341575.
Bioisosterism is widely used in medicinal chemistry as an approach aimed at either rationally modifying a hit compound into a more potent and/or selective molecule or a lead compound into a more drug-like one. Two different cannabinoid receptors have been cloned from mammalian tissues, the CB1 receptor, mostly expressed in brain, and the CB2 receptor, mostly expressed in the immune system, both regulating a variety of physiological functions. Synthetic cannabinoids have been developed that act as highly selective agonists or antagonists/inverse agonists at one or other of these receptor types with the ultimate goal of modulating the endocannabinoid system. This review takes into account the use of the bioisosteric substitution in the field of cannabinoid ligands as a tool for improving both their pharmacodynamic and pharmacokinetic properties.
生物等排原理在药物化学中被广泛应用，是一种旨在合理修饰先导化合物或命中化合物，以提高其活性和/或选择性，或使其更具类药性的方法。哺乳动物组织中已经克隆出两种不同的大麻素受体，CB1 受体主要在大脑中表达，CB2 受体主要在免疫系统中表达，两者都调节多种生理功能。已经开发出一些合成大麻素，它们作为高度选择性的激动剂或拮抗剂/反向激动剂，作用于这些受体类型中的一种或另一种，最终目的是调节内源性大麻素系统。本综述考虑了在大麻素配体领域中使用生物等排取代作为改善其药效学和药代动力学性质的工具。
