溴酚衍生物的合成及其蛋白酪氨酸磷脂酶1B抑制活性研究

Synthesis and PTP1B inhibitory activity of bromophenols derivatives

目的合成具有新型结构的系列溴酚衍生物,测试其体外蛋白酪氨酸磷脂酶1B(PTP1B)抑制活性并初步探讨其构效关系。方法以香草醛或3,4-二羟基苯甲醛为原料,经溴化、还原、醚化等反应制得目标化合物。借助重组人源PTP1B蛋白水解底物p NPP的方法,测定目标物对PTP1B的抑制活性。结果合成了18个溴酚衍生物,其结构经EI-MS、ESI-MS、~1H-NMR、^(13)C-NMR谱确证。结论目标化合物的PTP1B抑制活性与化合物中溴原子的数目、位置以及烷基链的长度有关;化合物6c体外PTP1B抑制活性最好(IC50=0.572μmol·L^(-1))。

Eighteen bromophenols derivatives were prepared by bromination, reduction and etherification via three steps or five steps starting from benzaldehyde derivatives. The structures were characterized by 1H-NMR, 13 C-NMR, EI-MS or ESI-MS. The PTPIB inhibitory activities were evaluated. The number or po- sition of Br atom in benzene ring and the length of alkyl chain have important influence on their PTP1B in- hibitory activities. Among these compounds, compound 6c showed the best inhibitory activity.