摘要
目的设计合成一系列全新的查耳酮类衍生物,并初步测试其蛋白酪氨酸激酶(PTKs)抑制活性。方法以间二甲苯为原料,经硝化、还原、水解、甲氧甲基保护等反应得到中间体取代苯乙酮,该中间体再与取代苯甲醛发生羟醛缩合反应后脱保护基得到目标化合物。采用酶联免疫吸附法(ELISA),以金雀异黄素为阳性对照,对目标化合物进行体外PTKs抑制活性检测。结果与结论合成了10个查耳酮衍生物,其中9个是未见报道的新化合物,10个化合物的结构经核磁共振氢谱和质谱确证。化合物6a及新化合物6b、6c和6d对PTKs具有良好的抑制活性。
As one kind of flavone family compounds,chalcone is a kind of high-value compounds bearing common skeleton of diphenyl acrylketone with a variety of pharmacological activities.In our previous work,flavanone derivatives were found have good inhibitory activity against protein tyrosine kinases（PTKs）.Now the structural modification of flavanone derivatives was made mainly on the B ring as a new way to prepare chalcone derivatives.Ten target compounds,among them nine are new derivatives,were synthesized by aldol condensation of benzaldehyde derivatives with substituted acetophenone which were obtained by successive nitration,reduction and hydrolysis of m-xylene,followed by methoxymethyl-group protection and then deprotection.Their structures were confirmed by1H-NMR and ESI-MS.And their protein tyrosine kinases（PTKs） inhibitory activity was investigated by ELISA with genistein as a positive control compound.The results showed that compounds 6a,6b,6c and 6d exhibited moderate inhibitory activities against protein tyrosine kinases,with inhibition rates varied from 28.44% to 53.12%,while genistein was 50.54%.The results showed that compounds with an ortho electron-withdrawing substituent on the B ring have good activity.
出处
《中国药物化学杂志》
CAS
CSCD
2011年第3期178-182,共5页
Chinese Journal of Medicinal Chemistry
基金
"重大新药创制"科技重大专项(2009ZX09302-003)
北京大学天然药物与仿生药物国家重点实验室开放基金(20080210)
山西省归国留学人员基金(2008-51)
山西医科大学博士启动基金(200631)
