摘要
GLP-1受体激动剂作为Ⅱ型糖尿病患者的有效用药,对中枢及外周神经系统也有良好的保护作用,在阿尔茨海默病和帕金森病等神经系统疾病的治疗中表现出潜在应用价值。以小分子GLP-1受体别构调节剂为先导化合物,通过系统的结构优化,设计并合成了14个新型的吲哚并吡啶酮类化合物,其结构经1H NMR,13C NMR和HR-MS(ESI)表征。并评价了化合物对GLP-1受体的作用。结果表明:部分化合物对GLP-1(7-36)或GLP-1(9-36)具有一定的别构调节作用。
As a potent drug for patients with type Ⅱ diabetes,GLP-1 receptor agonist can also exert good neuroprotective effects on both the central and peripheral nervous system,highlighting its potential value in the treatment of neurological diseases such as Alzheimer＇s disease,Parkinson＇s disease and so on. In this paper,fourteen novel indolopyridone compounds based on small-molecule GLP-1 receptor allosteric regulator were synthesized through systemic structural optimization,and the activity of these compounds were evaluated. The structures were characterized by1 H NMR,13 C NMR and HRMS（ ESI）. The results revealed that some of the compounds had allosteric modulatory effects on either GLP-1（ 7-36） or GLP-1（ 9-36）.
作者
王磊
郭彬
WANG Lei;GUO Bin(College of Pharmacy,Jiangxi Medical College,Nanchang University,Nanchang 330000,China;State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)
出处
《合成化学》
CAS
CSCD
北大核心
2018年第8期545-556,共12页
Chinese Journal of Synthetic Chemistry
关键词
GLP-1受体
别构调节剂
吲哚并吡啶酮
合成
构效关系
GLP-1 receptor
allosteric modulator
indolopyridone
synthesis
structure activity relationship
