节点文献
含3,4-二氢-2(1H)-喹啉酮结构查尔酮衍生物的合成及蛋白酪氨酸磷酸酯酶1B抑制活性研究
Synthesis and Protein Tyrosine Phosphatase 1B Inhibitory Activity of Novel Chalcone Derivatives Containing 3,4-Dihydroquinolin-2(1H)-one Moiety
【摘要】 蛋白酪氨酸磷酸酶1B(PTP1B)作为胰岛素和瘦素信号转导通路的负调节因子,已成为治疗糖尿病和肥胖症的潜在靶标.为了寻找非磷酸酯类PTP1B抑制剂,设计、合成了一系列含3,4-二氢-2(1H)-喹啉酮结构的新型查尔酮衍生物,并对化合物进行了PTP1B抑制活性测定.结果显示,所有化合物对PTP1B均显示出较强的抑制活性,其中化合物(E)-6-{4-[3-(4-氯苯基)-3-氧代-1-丙烯基]苄氧基}-3,4-二氢-2(1H)-喹啉酮(4e)和(E)-6-{4-[3-(3-溴苯基)-3-氧代-1-丙烯基]苄氧基}-3,4-二氢-2(1H)-喹啉酮(4i)活性最佳,IC50分别为(4.64±0.38)和(4.36±0.41)μmol/L.
【Abstract】 Protein tyrosine phosphatase 1B(PTP1B) has recently been identified as new drug target for type II diabetes and obesity due to it is a negative regulator of the insulin and leptin-signaling pathway.In order to find new nonphosphonate-based pTyr mimetics,a series of novel chalcone derivatives bearing the 3,4-dihydroquinolin-2(1H)-one moieties(4a～4n) were designed,synthesized,and evaluated for their PTP1B inhibitory activity.The results demonstrated that all compounds presented potent inhibitory activities against PTP1B,among which compounds 4e and 4i exhibited most potent with IC50value of(4.64±0.38) and(4.36±0.41) μmol/L,respectively.
【Key words】 chalcone； 3,4-dihydroquinolin-2(1H)-one； PTP1B inhibitor；
- 【文献出处】 有机化学 ,Chinese Journal of Organic Chemistry , 编辑部邮箱 ,2012年11期
- 【分类号】TQ460.1
- 【被引频次】17
- 【下载频次】345