Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Bioorg Med Chem Lett. 2011 Feb 15;21(4):1206-13. doi: 10.1016/j.bmcl.2010.12.089. Epub 2010 Dec 23.
To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.
为了改善 GSK80621b 的药物性质，我们合成了一系列杂芳基双环萘替代品。其中，喹啉 1c 是一种与 1b 等效力的 FXR 激动剂，具有改善的药物开发参数。此外，类似物 1c 还能降低糖尿病 DIO 小鼠模型的体重增加和血清葡萄糖水平。
