Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6895-8. doi: 10.1016/j.bmcl.2011.08.081. Epub 2011 Sep 5.
Based on molecular docking analysis of earlier results, we designed a series of 2,5-disubstituted furans/pyrroles (5a-h) as HIV-1 entry inhibitors. Compounds were synthesized by Suzuki-Miyaura cross coupling, followed by a Knoevenagel condensation or Wittig reaction. Four of these compounds were found to be effective in inhibiting HIV-1 infection, with the best compounds being 5f and 5h, which exhibited significant inhibition on HIV-1(IIIB) infection at micromolar levels with low cytotoxicity. These compounds are also effective in blocking HIV-1 mediated cell-cell fusion and the gp41 six-helix bundle formation, suggesting that they are also HIV-1 fusion inhibitors targeting gp41 and have potential to be developed as a new class of anti-HIV-1 agents.
基于早期结果的分子对接分析，我们设计了一系列 2,5-二取代呋喃/吡咯（5a-h）作为 HIV-1 进入抑制剂。通过 Suzuki-Miyaura 交叉偶联，随后进行 Knoevenagel 缩合或 Wittig 反应合成了这些化合物。其中四种化合物被发现能够有效抑制 HIV-1 感染，其中最好的化合物是 5f 和 5h，它们在微摩尔水平上对 HIV-1(IIIB)感染表现出显著的抑制作用，同时细胞毒性较低。这些化合物还能有效阻断 HIV-1 介导的细胞融合和 gp41 六螺旋束形成，表明它们也是针对 gp41 的 HIV-1 融合抑制剂，有可能开发成为一类新型抗 HIV-1 药物。
