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Synthesis, characterization and biological binding assay of bromo benzamides CCR5 antagonists[J]. Journal of South China normal University (Natural Science Edition), 2015, 47(3): 69-0. doi: 10.6054/j.jscnun.2014.12.053
Citation: Synthesis, characterization and biological binding assay of bromo benzamides CCR5 antagonists[J]. Journal of South China normal University (Natural Science Edition), 2015, 47(3): 69-0. doi: 10.6054/j.jscnun.2014.12.053

doi: 10.6054/j.jscnun.2014.12.053
基金项目: 

国家自然科学基金项目

详细信息
    通讯作者:

    程德军

  • 中图分类号: O621.3

Synthesis, characterization and biological binding assay of bromo benzamides CCR5 antagonists

  • 摘要: 非肽类小分子拮抗剂可以作为一种靶向制剂,用于防治人类HIV-1感染。溴代苯甲酰胺类非肽类小分子具有酰胺、哌啶、卤原子等活性基团而备受关注。本文合成了苯甲酰胺的邻位、间位以及邻位间位二取代溴化物中间体7,以对氯苄氯为原料合成了4-溴-2-溴甲基-1-((4-氯苄基)氧)苯(中间体3),通过中间体3、中间体7合成了三种新的溴代苯甲酰胺类拮抗剂,对三种溴代物进行了1H NMR、IR、 MS表征及生物活性检测。结果表明N-烯丙基-N-(1-(5-溴-2-(4-氯苄氧基)苄基)-4-哌啶基)-2,5-二溴苯甲酰胺具有一定的生物活性。
  • [1] Mohammed Abdul Rasheed,Nagul Meera Shaik,Concise and aimple synthesis OFM1 allosteric agonist TBPB[J].Synthetic Communications,2013,43:1796-1801.
    [2] 焦诗卉,何淼.HIV辅助受体CCR5常见小分子抑制剂抑制效果的综合评价[J].中山大学学报(自然科学版),2012,51(6):97-102.
    [3] Yongjun Ji,Mao Shu,Yong Lin,et al.Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists[J].Journal of Molecular Structure,2013,1045(11):35-41.
    [4] Renato Skerlj,Gary Bridger,Yuanxi Zhou,et al.Design and synthesis of pyridin-2-ylmethylaminopiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic(R5)HIV-1 replication[J].Bioorganic & Medicinal Chemistry Letters,2011,21(23):6950-6954.
    [5] Mohsen Shahlaei,Alireza Pourhossein.Modeling of CCR5 antagonists as anti HIV agents using combined genetic algorithm and adaptive neuro-fuzzy inference system(GA-ANFIS)[J].Med Chem Res,2013,22:4423-4436.
    [6] Lavina Gharu,Rajesh Ringe,Jayanta Bhattacharya.HIV-1 clade C envelopes obtained from late stage symptomatic Indian patients varied in their ability towards relative CD4 usages and sensitivity to CCR5 antagonist TAK-779[J].Virus Research,2011,158(1):216-224.
    [7] 袁利,吴建中,陈国泉. 2,9-二(2-咪唑并[4,5-f]邻菲咯啉)邻菲咯啉的合成和表征[J].华南师范大学学报(自然科学版),2002,(04): 104-108.
    [8] Shou-Fu Lu,Binglong Chen,Dave Davey,et al.CCR5 receptor antagonists:Discovery and SAR of novel 4-hydroxypiperidine derivatives[J].Bioorganic & Medicinal Chemistry Letters,2007,17(7):1883-1887.
    [9] Paul E.Finkea,Bryan Oates,Sander G.Mills.Antagonists of the Human CCR5 Receptor as Anti-HIV-1 Agents.Part 4:Synthesis and Structure–Activity Relationships for 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes[J].Bioorganic & Medicinal Chemistry Letters,2001,11(18):2475-2479.
    [10] Mark A.Ashwell,Jean-Marc Lapierre,Alan Kaplan.The design,preparation and SAR of novel small molecule sodium(Na+) channel blockers[J].Bioorganic & Medicinal Chemistry Letters,2004,14(9):2025-2030.
    [11] 吕燕慧.CCR5拮抗剂TD0232的体外药效学研究[D].上海:中国科学院上海生命科学研究院,2005:28-30.
    [12] CHENG Z J, FAN G H, ZHAO J.Endogenous opioid receptor-like receptor in human neuroblastoma SK-N-SH cells: activation of inhibitory G protein and homologous desensitization[J].Neuroreport,1997(8):1913-1918.

    [1] Mohammed Abdul Rasheed,Nagul Meera Shaik,Concise and aimple synthesis OFM1 allosteric agonist TBPB[J].Synthetic Communications,2013,43:1796-1801.
    [2] 焦诗卉,何淼.HIV辅助受体CCR5常见小分子抑制剂抑制效果的综合评价[J].中山大学学报(自然科学版),2012,51(6):97-102.
    [3] Yongjun Ji,Mao Shu,Yong Lin,et al.Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists[J].Journal of Molecular Structure,2013,1045(11):35-41.
    [4] Renato Skerlj,Gary Bridger,Yuanxi Zhou,et al.Design and synthesis of pyridin-2-ylmethylaminopiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic(R5)HIV-1 replication[J].Bioorganic & Medicinal Chemistry Letters,2011,21(23):6950-6954.
    [5] Mohsen Shahlaei,Alireza Pourhossein.Modeling of CCR5 antagonists as anti HIV agents using combined genetic algorithm and adaptive neuro-fuzzy inference system(GA-ANFIS)[J].Med Chem Res,2013,22:4423-4436.
    [6] Lavina Gharu,Rajesh Ringe,Jayanta Bhattacharya.HIV-1 clade C envelopes obtained from late stage symptomatic Indian patients varied in their ability towards relative CD4 usages and sensitivity to CCR5 antagonist TAK-779[J].Virus Research,2011,158(1):216-224.
    [7] 袁利,吴建中,陈国泉. 2,9-二(2-咪唑并[4,5-f]邻菲咯啉)邻菲咯啉的合成和表征[J].华南师范大学学报(自然科学版),2002,(04): 104-108.
    [8] Shou-Fu Lu,Binglong Chen,Dave Davey,et al.CCR5 receptor antagonists:Discovery and SAR of novel 4-hydroxypiperidine derivatives[J].Bioorganic & Medicinal Chemistry Letters,2007,17(7):1883-1887.
    [9] Paul E.Finkea,Bryan Oates,Sander G.Mills.Antagonists of the Human CCR5 Receptor as Anti-HIV-1 Agents.Part 4:Synthesis and Structure–Activity Relationships for 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes[J].Bioorganic & Medicinal Chemistry Letters,2001,11(18):2475-2479.
    [10] Mark A.Ashwell,Jean-Marc Lapierre,Alan Kaplan.The design,preparation and SAR of novel small molecule sodium(Na+) channel blockers[J].Bioorganic & Medicinal Chemistry Letters,2004,14(9):2025-2030.
    [11] 吕燕慧.CCR5拮抗剂TD0232的体外药效学研究[D].上海:中国科学院上海生命科学研究院,2005:28-30.
    [12] CHENG Z J, FAN G H, ZHAO J.Endogenous opioid receptor-like receptor in human neuroblastoma SK-N-SH cells: activation of inhibitory G protein and homologous desensitization[J].Neuroreport,1997(8):1913-1918.
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出版历程
  • 收稿日期:  2015-01-03
  • 修回日期:  2015-01-08
  • 刊出日期:  2015-05-25

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