新型1,2 - 二硫杂环戊烷 - 4 - 基苯甲酸酯衍生物作为蛋白酪氨酸磷酸酶1B抑制剂的设计与合成
Design and synthesis of novel 1,2-dithiolan-4-yl benzoate derivatives as PTP1B inhibitors.
作者信息
Chen Jing, Gao Li-Xin, Gong Jing-Xu, Jiang Cheng-Shi, Yao Li-Gong, Li Jing-Ya, Li Jia, Xiao Wei, Guo Yue-Wei
机构信息
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
School of Biological Science and Technology, University of Jinan, Jinan 250022, Shandong, PR China.
出版信息
Bioorg Med Chem Lett. 2015;25(10):2211-6. doi: 10.1016/j.bmcl.2015.03.060. Epub 2015 Mar 27.
A series of novel 1,2-dithiolan-4-yl benzoate compounds were synthesized and evaluated for in vitro PTP1B inhibitory activity. Some derivatives exhibited improved PTP1B inhibitory activity and selectivity compared to hit 6a, a compound from in-house library screening inspired by marine cyclic disulfide. The preliminary SAR analysis with assistance of molecular modeling approach revealed 6j (IC50=0.59μM) as the most potent PTP1B inhibitor among all derivatives.
合成了一系列新型的1,2 - 二硫杂环戊烷 - 4 - 基苯甲酸酯化合物，并对其体外蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性进行了评估。与化合物6a相比，一些衍生物表现出更好的PTP1B抑制活性和选择性，化合物6a是从受海洋环状二硫化物启发的内部库筛选中得到的。在分子建模方法的辅助下进行的初步构效关系（SAR）分析表明，6j（IC50 = 0.59μM）是所有衍生物中最有效的PTP1B抑制剂。
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