Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Japan.
Bioorg Med Chem. 2013 Sep 15;21(18):5900-6. doi: 10.1016/j.bmc.2013.06.061. Epub 2013 Jul 3.
A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N(3)-position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 μM and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization.
合成了一系列新型的 N(3)-位带有 3,5-二甲基苄基的尿嘧啶衍生物，并将其作为非核苷类 HIV-1 逆转录酶抑制剂进行了评估。其中一些化合物表现出良好至中等的活性，半数有效浓度（EC50）值在亚微摩尔范围内。在这些化合物中，化合物 10c 对 HIV-1 活性表现出显著的效力，半数有效浓度（EC50）值为 0.03 μM，选择性指数高达 2863。初步的构效关系和分子模拟分析用于探索 HIV-1 逆转录酶与强效抑制剂 10c 之间的主要相互作用，这可能为进一步优化提供重要线索。
