α7烟碱型乙酰胆碱受体(α7nAChR)主要分布在海马和相关皮层,与老年斑的沉积部位一致,且对钙离子有相当高的通透性,可以调节钙的活化及递质乙酰胆碱的释放,能直接影响认知和记忆功能,因此逐渐成为阿尔茨海默症等神经退行性疾病发病机制的研究热点。GTS-21是由海洋纽形动物类(Nemertea)两孔纽虫(Amphipoius)分泌的毒素新烟碱(Anabaseine)与2,4-二甲氧苯甲醛缩合而成的选择性α7nAChR的部分激动剂,作为候选药物被用于治疗阿尔茨海默症及精神分裂症等神经退行性疾病,目前已进入各期临床开发阶段。近年来,为了获得高效、低毒和更易透过血脑屏障的GTS-21衍生物,药物化学家们进行了大量的优化研究,获得了一些具有良好活性的衍生物。本文就GTS-21及其类似物优化的研究进展进行综述。 α7 nicotinic acetylcholine receptor (α7nAChR) mainly in the hippocampus and related cortex, and the deposition site of senile plaques, and a very high permeability of calcium ions, can regulate the activation of calcium and acetylcholine release, Directly affect the cognitive and memory functions, it has gradually become the research focus of the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease. GTS-21 is a partial agonist of selective [alpha] 7 nAChR produced by condensation of the toxin neabase (Anabaseine) secreted by the Nemertea Amphipoius with 2,4-dimethoxybenzaldehyde , Has been used as a drug candidate in the treatment of neurodegenerative diseases such as Alzheimer’s disease and schizophrenia and has entered the phase of clinical development. In recent years, a large number of optimization studies have been carried out by pharmaceutical chemists in order to obtain GTS-21 derivatives that are efficient, less toxic and more easily cross the blood-brain barrier and obtain some derivatives with good activity. This article reviews the progress of GTS-21 and its analogues.