CXCR4 HIV-1抑制剂的设计合成及活性研究  

Design,synthesis and activity evaluation of new anti-HIV-1 CXCR4 inhibitors

作　　者：叶建涵 周尚民[1] 王茜[3] 陆路[3] 董铭心[2] 陈红飙[1] 姜世勃[3] 戴秋云[2] 

机构地区：[1]湘潭大学化学学院,湖南湘潭411105 [2]军事医学科学院生物工程研究所,北京100071 [3]复旦大学基础医学院医学分子病毒学教育部/卫生部重点实验室,上海200032

出　　处：《军事医学》2014年第8期602-607,共6页Military Medical Sciences

基　　金：国家自然科学基金资助项目(81102373)

摘　　要：目的设计、合成一系列新型四氢喹啉-苄基或苯并咪唑多胺类化合物,作为潜在的靶向CXCR4辅助受体的新型抑制剂,并测定其抗HIV-1活性。方法组合HIV-1辅助受体CXCR4抑制剂三氮构效团与CCR5部分药效团,设计并合成一系列新化合物并经1H-NMR、MS表征,用HIV-1ⅢB病毒测定化合物抑制活性。结果与结论设计合成的10个目标化合物未见文献报道。活性测试结果显示,四氢喹啉-苯并咪唑多胺类化合物具有较好的抗HIV活性(IC50<1μmol/L),四氢喹啉-苄基多胺类化合物活性较差(IC50>8μmol/L)。Objective To design and synthesize a series of new type four hydrogen quinoline-benzyl/benzimidazole amine derivatives as a potential new inhibitor targeting auxiliary receptor CXCR 4, and determine their inhibitory activities to HIV-1.Methods Based on HIV-1 receptor CXCR4 inhibitors containing three nitrogen structure-activity motif and CCR5 partial hydrophobic pharmacophore , a series of new compounds were designed , synthesized and characterized by 1 HNMR and MS.The inhibitory activities of these compounds were determined using HIV-1 IIIB virus.Results and Conclusion Ten target compounds are synthesized .Four hydrogen quinoline-benzimidazole amine derivatives exhibit good anti-HIV activity（IC50 ＆lt;1 μmol/L）, but four hydrogen quinoline-benzyl amine compounds are less active （（IC50 ＆gt;8 μmol/L）.

关 键 词：CXCR4 HIV-1 抑制剂 合成 活性 

分 类 号：R914[医药卫生—药物化学]