【摘要】 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。更多还原

【Abstract】 α7 nicotinic acetylcholine receptor(α7nAChR)distributed mainly in hippocampus and related slices.It is consistent with the deposition site of senile plaques.It also can regulate the activation of calcium and the release of acetylcholine,then impact the cognition and memory function.So it has been attracted attention in the research of neurodegenerative disease.GTS-21 is a selective α7nAChR agonist which is derived from a new marine toxin nicotine(anabaseine)with 2,4-dimethoxy benzaldehyde,and it can be applied to treat Alzheimer’s disease,schizophrenia and other neurodegenerative disorders as a drug candidate.In order to obtain high efficiency,low toxicity and pass through the blood brain barrier easily of GTS-21 analogues,a number of derivatives have been designed and synthesized by medicinal chemists in recent years.In this review,the progress of the development of GTS-21 and its analogues is reported.更多还原