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(E)-1-取代苯基-3-[4-((E)-(2-(4-苯基噻唑-2-基)腙)甲基)苯基]-2-丙烯-1-酮(4a～4n),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4h活性最佳,IC50为(2.57±0.50)μmol L-1.
Abstract Protein tyrosine phosphatase 1B （PTP1B） has recently been identified as new drug target for type II diabetes and obesity due to that it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphospho- nate-based pTyr mimetics, a series of novel （E）-1-phenyl-3-（4-（（E）-（2-（4-phenyl-thiazol-2-yl）hydrazono）methyl）phenyl）- prop-2-en-l-one （4a-4n） were designed, synthesized, and evaluated for their PTP1B inhibitory activity. The results demon- strated that all compounds presented potent inhibitory activities against PTP1B, among which compound 4h exhibited most potent with IC50 value of （2.57 ±0.50） μmol·L^-1.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2013年第7期1496-1502,共7页
Chinese Journal of Organic Chemistry
基金
国家自然科学基金(Nos.81160381,81125023)资助项目~~
关键词
PTP1B抑制剂
查尔酮
醛腙
噻唑
PTP 1 B inhibitor
chalcone
carboxaldehyde hydrazone
thiazole
