GABA受体小分子调节剂合成

γ-氨基丁酸(γ-aminobutyric acid,GABA)是哺乳动物和昆虫中枢神经系统中重要的抑制性神经递质。20世纪70年代末发现GABAA受体是重要医药作用靶标,也是农药杀虫剂的作用靶标。GABAA受体上至少存在4种互相变构体的结合位点,与这些结合位点结合的不同化合物,对氯离子通道的作用机制不同,表现出不同的生物活性。具有杀虫活性的化合物有氟虫腈、林丹、狄氏剂和阿维菌素等,具有医用生物活性的化合物有用于治疗抑郁症的巴比妥、氟硝西泮和氟马西尼以及安定类镇静剂和印防己毒素等抗痉挛剂。分类概述了部分GABA受体小分子调节剂的制备方法与生物活性及其合成路线的研究进展,并对未来开发GABA受体调节剂进行了展望。

The Synthesis of Small Molecule Modulators of the GABA Receptor

Gamma-aminobutyric acid y-aminobutyric acid, GABA） is an important inhibitory neurotransmitter in the central nervous system of mammals and insects. The late 1970s found that the GABAA receptor is an important medicinal target and also the target of pesticides. There are at least four binding sites which are dynamic isomer existing on GABAA receptor. The compounds binding with these sites have different action mechanisms on chloride channel, so show different biological activity. Fipronil, lindane, dieldrin, avermectin and so on are the insecticidal products. Barbiturates, flunitrazepam and flumazenil for controlling depression, antipsychotic tranquilizers and anticonvulsant picrotoxin are medical bioactive compounds.This article reviews the research progress of the preparation, biological activity and the synthetic routes of the part of the GABA receptor small molecule modulators, and looks forward to the future development of GABA receptor modulators.