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目前治疗Ⅱ型糖尿病的主要手段依然是口服或注射降糖药物以达到控制血糖的目的.虽然已有针对不同靶点开发的多种抗Ⅱ型糖尿病药物上市,但是鉴于糖尿病治疗药物长期服用的高安全性要求以及庞大的患病人群,研发新型安全有效的抗糖尿病药物仍然是当今药物化学研究的热点.GPR40是G-蛋白偶联受体家族中的一员,激动后可以诱导葡萄糖依赖的胰岛素分泌.因为仅在血糖浓度过高时,GPR40激动剂才能促进胰岛素分泌,所以针对该靶点开发降糖药物将极大地降低目前抗糖尿病药物低血糖副作用的风险.因此,GPR40已成为抗Ⅱ型糖尿病药物研发的前沿和热门靶点,本文将围绕小分子GPR40激动剂的药效团模型,即必需的苯丙酸核心骨架及其疏水末端和连接链的结构改造,对近年来各大制药公司及研究机构报道的小分子GPR40激动剂的研发进展进行总结评述.
Currently the main treatment of type 2 diabetes is still the oral or injection of hypoglycemic drugs in order to achieve the purpose of controlling blood glucose.Although there are a variety of targets for the development of a variety of anti-type 2 diabetes drugs listed, but in view of long-term use of diabetes treatment drugs high Safety requirements and a large population of patients, research and development of new safe and effective anti-diabetic drugs is still the focus of current drug chemistry research.GPR40 is a member of the G-protein coupled receptor family, excited to induce glucose-dependent insulin Because GPR40 agonists promote insulin secretion only when blood glucose levels are too high, developing antidiabetic drugs against this target will greatly reduce the risk of hypoglycemic side effects of current antidiabetic drugs, and GPR40 has therefore become resistant to type II Diabetes drug research and development of the frontier and the hot targets, this article will focus on the small molecule GPR40 agonist pharmacophore model, which is necessary for the phenylpropanoic acid core skeleton and its hydrophobic ends and the structural transformation of the connecting chain, in recent years, major pharmaceutical companies And research institutions reported the progress of research and development of small molecule GPR40 agonists summarized.