含有芳杂环片段的喹诺酮类化合物的设计、合成与体外抗病毒活性

摘要

目的 设计合成一系列含有芳杂环片段的喹诺酮类化合物,并评价其体外抗人类巨细胞病毒(HCMV)和抗单纯疱疹病毒1型(HSV-1)活性.方法 N-芳杂环基哌嗪与喹诺酮母核化合物通过亲核取代反应制备目标物,其结构经1H-NMR、13C-NMR、MS和HRMS确证.CPE法测定所有目标物对细胞的TC50及对HCMV和HSV-1的IC50值.结果 合成了22个喹诺酮类化合物(包括先导物WC5).部分目标物对HCMV和(或)HSV-1有抑制作用,其中化合物19对HSV-1的IC50为(2.18±0.30)μg/ml,略弱于WC5的(1.68±0.25)μg/ml.结论 丰富了喹诺酮类化合物抗病毒构效关系,并为下一步设计合成活性喹诺酮类化合物奠定基础.%Objective To design and synthesize a series of novel quinolones containing a heteroaromatic moiety, and evaluate their in vitro antiviral (HCMV and HSV-1) activity. Methods Target compounds were synthesized through nucleophilic substitution of N-heteroaromaticpiperazines with different quinolone cores. Their structures were characterized by1H-NMR,13C-NMR, MS and HRMS.In vitroantiviral (HCMV and HSV-1) activity of the compounds was evaluated by CPE assay. Results Twenty-two compounds including WC5 were synthesized in this study. Some compounds were found to have inhibition against HCMV and/or HSV-1. Compound 19 [IC50: (2.18 ± 0.30) μg/ml] is slightly less active than WC5 [IC50: (1.68 ± 0.25) μg/ml] against HSV-1. Conclusion The study enriches the structure activity relationship of quinolone against HCMV/HSV-1, which lays the foundation for the future design of novel quinolones with potent activity.