Design, Synthesis and Anti-HIV-1 Activity of (E)-N′-Arylmethylene-4-(4-Phenylpyrimidin-2-ylamino) benzohydrazide Derivatives as CDK9 Inhibitors
ZHU Ke-yu1, ZHAO Sheng-xian2, HE Feng-ming3, ZHENG Xiao-xiang1,4*, YANG Xue-wen2, ZHANG Zhao-lin1, HU Hong-yu1*
1. Xingzhi College, Zhejiang Normal University, Lanxi 321100, China; 2. Zhejiang Apeloa Tospo Pharmaceutical Co.,Ltd., Dongyang 322118, China; 3. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; 4. College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China
Abstract：OBJECTIVE To design and synthesize(E)-N′-arylmethylene-4-(4-phenylpyrimidin-2-ylamino) benzohydrazide derivatives and investigate their anti-HIV-1 activities. METHODS The target compound was synthesized by five step reactions using ethyl aminobenzoate as starting material. The transcriptional inhibitory activities of the synthetic compounds against HIV-1 were detected by luciferase reporter gene. RESULTS The target compounds showed certain inhibitory activities on HIV-1 transcription, among which compound 7P had the best inhibitory activity, with inhibitory rate of (73±0.05)% at 2 μmol·L-1 and (90±0.01)% at 20 μmol·L-1, respectively. Further study showed that compound 7P inhibited HIV-1 transcriptional activity and down-regulated RNA polymerase Ⅱ CTD serine 2 phosphorylation in a concentration-dependent manner in NH1 and NH2 cells. Finally, molecular docking showed that compound 7P had a strong binding effect with CDK9. CONCLUSION This series of compounds have good anti-HIV-1 activities, which has significant research value for further study.
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2022, Vol. 57 
