Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design
Discovery of novel selective GPR120 agonists with potent anti-diabetic activity by hybrid design
复制标题
通过混合设计发现具有有效抗糖尿病活性的新型选择性 GPR120 激动剂
DOI：
10.1016/j.bmcl.2018.06.047
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发表时间：
2018-08-15
影响因子：
2.7
通讯作者：
Sun, Hongbin
中科院分区：
文献类型：
--
作者：
Sheng, Ren;Yang, Liu;Sun, Hongbin
GPR120是治疗2型糖尿病的一个有吸引力的靶点。本研究采用混合设计法设计、合成了一系列联苯衍生物。所选化合物6a表现出有效的GPR120激动剂活性（EC 50 = 93 nM）和对GPR40的高选择性。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。并对构效关系进行了分析。化合物6a值得进一步的生物学评价和结构修饰。
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 (EC50 = 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.