通过杂交设计发现具有强效抗糖尿病活性的新型选择性GPR120激动剂。
Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design.
作者信息
Sheng Ren, Yang Liu, Zhang Yanchun, Xing Enming, Shi Rui, Wen Xiaoan, Wang Heyao, Sun Hongbin
机构信息
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
出版信息
Bioorg Med Chem Lett. 2018 Aug 15;28(15):2599-2604. doi: 10.1016/j.bmcl.2018.06.047. Epub 2018 Jun 28.
GPR120 is an attractive target for the treatment of type 2 diabetes. In this study, a series of biphenyl derivatives were designed, synthesized by hybrid design. The selected compound 6a exhibited potent GPR120 agonist activity (EC = 93 nM) and high selectivity over GPR40. The results of oral glucose tolerance test (OGTT) demonstrated that 6a exhibited significant glucose-lowering effect in glucose-loaded ICR male mice. Analysis of the structure-activity relationship is also presented. Compound 6a deserves further biological evaluation and structural modifications.
GPR120是治疗2型糖尿病的一个有吸引力的靶点。在本研究中，通过杂化设计设计并合成了一系列联苯衍生物。所选化合物6a表现出强效的GPR120激动剂活性（EC = 93 nM），并且对GPR40具有高选择性。口服葡萄糖耐量试验（OGTT）结果表明，6a在葡萄糖负荷的ICR雄性小鼠中表现出显著的降糖作用。还介绍了构效关系分析。化合物6a值得进一步进行生物学评价和结构修饰。
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