Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Russia.
Bioorg Med Chem. 2010 Dec 1;18(23):8310-4. doi: 10.1016/j.bmc.2010.09.070. Epub 2010 Oct 7.
Pyrimidine analogs have long found use over a broad chemotherapeutic spectrum. In an effort to further explore the antiviral potential of several uracil derivatives previously synthesized in our laboratories, a series of benzylated pyrimidines were designed and synthesized. Introduction of the benzyl residue onto the 5-phenylaminouracil scaffold was carried out using 2,4-bis(trimethylsilyloxy)pyrimidine with the corresponding benzyl bromides. Similarly, 1-benzyl-5-(benzylamino)- and 1-benzyl-5-(phenethylamino)uracils were obtained via amination of 1-benzyl-5-bromouracils with benzylamine or phenylethylamine. The results of the broad screen antiviral studies revealed that compounds 5 and 11 exhibit promising inhibitory activity against HIV-1 in CEM-SS culture. A 50% protective effect was observed at concentrations of 11.9 and 9.5 μМ, respectively. Moreover, compounds 8 and 3 exhibited good inhibitory effects against EBV in АKАТА cell culture with EC₅₀ values of 2.3 and 12 μM, respectively. The synthesis and biological studies are detailed herein.
嘧啶类似物在广泛的化疗范围内长期得到应用。为了进一步探索我们实验室之前合成的几种尿嘧啶衍生物的抗病毒潜力，设计并合成了一系列苯甲基嘧啶。用相应的溴化苄基，在 5-苯氨基尿嘧啶骨架上引入苄基残基，使用 2,4-双（三甲基甲硅烷基氧基）嘧啶。同样，通过 1-苯甲基-5-溴尿嘧啶与苄胺或苯乙胺的胺化反应，得到 1-苯甲基-5-（苄基氨基）和 1-苯甲基-5-（苯乙基氨基）尿嘧啶。广谱抗病毒研究的结果表明，化合物 5 和 11 在 CEM-SS 培养物中对 HIV-1 表现出有希望的抑制活性。在浓度分别为 11.9 和 9.5 μM 时，观察到 50%的保护作用。此外，化合物 8 和 3 在 AKATATA 细胞培养物中对 EBV 表现出良好的抑制作用，EC₅₀ 值分别为 2.3 和 12 μM。本文详细介绍了它们的合成和生物学研究。
