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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.
As a negative regulator of insulin and leptin signal transduction pathway, protein tyrosine phosphatase 1B (PTP1B) has become a potential target for the treatment of diabetes and obesity.In order to find a non-phosphate ester PTP1B inhibitor, we designed and synthesized a Series of novel chalcone derivatives containing 3,4-dihydro-2 (1H) -quinolinone were prepared and the compounds were tested for PTP1B inhibitory activity. The results showed that all of the compounds showed strong inhibition on PTP1B Wherein the compound (E) -6- {4- [3- (4-chlorophenyl) -3- oxo- 1 -propenyl] benzyloxy} -quinolinone (4e) and (E) -6- {4- [3- (3- bromophenyl) -3-oxo- 1 -propenyl] benzyloxy} -3,4-dihydro- 2 (1H) -quinolinone (4i) showed the best activity with IC50 of (4.64 ± 0.38) and (4.36 ± 0.41) μmol / L, respectively.