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目的设计合成一系列具有新型结构特征的双环哌啶类C-C族趋化因子受体5(CCR5)抑制剂并测定其抗HIV-1活性。方法以HIV-1辅助受体CCR5抑制剂Vicriviroc的结构为模板,通过改变左侧哌嗪结构、取代基位置等方法设计并合成一系列新化合物。并利用MS及1H-NMR谱对这些化合物进行结构表征。结果与结论合成了15个新结构化合物,活性测试结果表明,该系列化合物具有较强的抗HIV-1 R5病毒株的活性(IC50=1.20～66.24μmol.L-1)。当R1为芳基结构且两个氮原子满足标准的丙二胺结构时,化合物的活性更好。
OBJECTIVE: To design and synthesize a series of novel bicyclic piperidine C-C chemokine receptor 5 (CCR5) inhibitors with novel structural characteristics and to determine their anti-HIV-1 activity. Methods The structure of Vicriviroc, a CCR5 inhibitor of HIV-1, was used as a template to design and synthesize a series of new compounds by changing the structure of the left piperazine and the position of substituents. These compounds were characterized by MS and 1H-NMR spectra. RESULTS AND CONCLUSION: Fifteen new structural compounds were synthesized. The results of the activity test showed that the compounds possess strong activity against the HIV-1 R5 strain (IC50 = 1.20 ~ 66.24μmol.L-1). Compounds are more active when R1 is an aryl structure and both nitrogen atoms satisfy the standard propylenediamine structure.