|
|
- 2015
|
Abstract:
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] | 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. |
| [2] | Mohammed Abdul Rasheed,Nagul Meera Shaik,Concise and aimple synthesis OFM1 allosteric agonist TBPB[J].Synthetic Communications,2013,43:1796-1801. |
| [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] | 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. |
| [6] | 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. |
| [7] | 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. |
| [8] | 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. |
| [9] | 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. |
| [10] | 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. |
| [11] | 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. |
| [12] | 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. |
