Research Center of Biotechnology RAS, Leninsky Prospekt 33-2, 119071, Moscow, Russia.
Institute of Virology, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Chariteplatz 1, 10117, Berlin, Germany.
Eur J Med Chem. 2021 Feb 5;211:113014. doi: 10.1016/j.ejmech.2020.113014. Epub 2020 Nov 12.
Viruses are obligate intracellular parasites and have evolved to enter the host cell. To gain access they come into contact with the host cell through an initial adhesion, and some viruses from different genus may use heparan sulfate proteoglycans for it. The successful inhibition of this early event of the infection by synthetic molecules has always been an attractive target for medicinal chemists. Numerous reports have yielded insights into the function of compounds based on the dispirotripiperazine scaffold. Analysis suggests that this is a structural requirement for inhibiting the interactions between viruses and cell-surface heparan sulfate proteoglycans, thus preventing virus entry and replication. This review summarizes our current knowledge about the early history of development, synthesis, structure-activity relationships and antiviral evaluation of dispirotripiperazine-based compounds and where they are going in the future.
病毒是专性细胞内寄生虫，已经进化到可以进入宿主细胞。为了进入宿主细胞，它们通过最初的黏附与宿主细胞接触，一些来自不同属的病毒可能会利用硫酸乙酰肝素蛋白聚糖来实现这一点。通过合成分子成功抑制感染的这个早期事件一直是药物化学家的一个有吸引力的目标。许多报告深入了解了基于双稠哌嗪骨架的化合物的功能。分析表明，这是抑制病毒与细胞表面硫酸乙酰肝素蛋白聚糖之间相互作用的结构要求，从而阻止病毒进入和复制。这篇综述总结了我们目前对基于双稠哌嗪的化合物的早期开发、合成、构效关系和抗病毒评估的了解，以及它们未来的发展方向。
