Development of anti-HIV agents targeting dynamic supramolecular mechanism and feedback mechanism

在治疗HIV感染性疾病和艾滋病药物的开发中，我们合成了具有动态超分子机制的HIV进入抑制剂，如CXCR4拮抗剂和其他具有不同作用机制的新型药物。1.开发了以二甲苯为骨架的新型CXCR4拮抗剂和有效的二价CXCR4拮抗剂。2.发现小分子的CD4模拟衍生物具有显著的抑制HIV侵入的活性，并能增加与中和抗体的结合亲和力。3.从VPR片段中发现了整合酶抑制剂。4.开发了具有细胞膜穿透信号的基质片段衍生的抗HIV药物。

In the development of drugs for treatments of HIV infectious disease and AIDS, we have synthesized HIV entry inhibitors having dynamic supramolecular mechanism such CXCR4 antagonists and other novel agents having different action mechanism. 1. Novel CXCR4 antagonists having xylene scaffold and potent bivalent CXCR4 antagonists were developed. 2. Small CD4 mimic derivatives having significant inhibitory activity against HIV entry and causing an increase of binding affinity for neutralizing antibodies were found. 3. Integrase inhibitors were discovered from Vpr fragments. 4. Anti-HIV agents derived from matrix fragments with cell membrane penetrating signals were developed.