新型1-(1,3,5-三嗪-6-基)-3-甲基-4-(5-苯基-1,3,4-噁二唑-2-基)吡唑的合成及活性评价

设计合成了18个以吡唑桥连1,3,4-噁二唑和1,3,5-三嗪的新型多杂环分子7A(a~f),7B(a~f)和7C(a~f)];通过红外光谱(IR)、核磁共振波谱(NMR)和高分辨质谱(HRMS)等对目标分子进行了结构表征;评价了目标分子对蛋白酪氨酸磷酸酯酶1B(PTP1B)和细胞分裂周期25磷酸酯酶B(Cdc25B)的抑制活性.结果表明,所有目标分子对PTP1B和Cdc25B均有较好的抑制活性,其中,9个目标分子表现出优异的PTP1B和Cdc25B抑制效果,IC50值低于齐墩果酸(PTP1B抑制活性测试参照物)和正钒酸钠(Cdc25B抑制活性测试阳性参照物),有望成为潜在的PTP1B和Cdc25B抑制剂.

Synthesis and Bioactivities Evaluation of Novel 1-( 1,3,5-Triazin-6-yl)-3-methyl-4-( 5-phenyl-1,3,4-oxadiazol-2-yl) pyrazole

Eighteen novel multi-heterocyclic molecules7A(a—f), 7B(a—f), 7C(a—f)] were designed and synthesized by hybrid-linking 1,3,4-oxadiazole and 1,3,5-triazine onto pyrazole. The structures of all the compounds were confirmed by IR, NMR and HRMS. The inhibitory activities of target molecules against protein tyrosine phosphatase 1B( PTP1B) and cell division cycle 25 phosphatase B( Cdc25B) were evaluated. As a result, all of the target molecules behave good inhibitory activities against PTP1B and Cdc25B, in which nine compounds show excellent inhibitory activities, respectively. The inhibitory activities of nine compounds are better than the reference oleanolic acid and Na3 VO4 , respectively. The nine compounds are expected to be-come potential inhibitors of PTP1B and Cdc25B.