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Acta Chimica Sinica ›› 2008, Vol. 66 ›› Issue (24): 2725-2729. Previous Articles     Next Articles

Original Articles

新型α1受体拮抗剂先导化合物的寻找(I): 5-氯-2-(4-(芳氧烷基)哌嗪-1-基)苯并噁唑类化合物的设计、合成及生物活性研究

李嘉宾a 江振洲b 王 涛b 刘明明a
夏 俊c 吴 斌d 夏 霖*,e

  

  1. (a中国药科大学 无机化学教研室 南京 210009)
    (b中国药科大学 新药筛选中心 南京 210009)
    (c中国药科大学 新药研究中心 南京 210009)
    (d南京医科大学 药物化学教研室 南京 210029)
    (e中国药科大学 药物化学教研室 南京 210009)

  • 投稿日期:2008-09-23 修回日期:2008-11-04 发布日期:2008-12-28
  • 通讯作者: 夏霖

Searching for the Novel Lead Compounds of α1-AR Antagonists (Part I): Design, Synthesis and Bioassay of 5-Chloro-2-[4-(aryloxyalkyl)piperazin-1-yl] benzo[d]oxazole Compounds

LI, Jia-Bin a JIANG, Zhen-Zhou b WANG, Tao b LIU, Ming-Ming a
XIA, Jun c WU, Bin d XIA, Lin *,e
  

  1. (a Department of Inorganic Chemistry, China Pharmaceutical University, Nanjing 210009)
    (b National Drug Screening Center, China Pharmaceutical University, Nanjing 210009)
    (c New Drug Research Center, China Pharmaceutical University, Nanjing 210009)
    (d Department of Medicinal Chemistry, Nanjing Medical Univeristy, Nanjing 210029)
    (e Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009)
  • Received:2008-09-23 Revised:2008-11-04 Published:2008-12-28
  • Contact: XIA, Lin

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To search for the new α1-adrenoceptor antagonists, 11 target compounds bearing a 2-(piperazin-1-yl) benzo[d]oxazole scaffold were designed from our lead compound 2-[(4-(2-(2-chloropheno-
xy)-ethyl)-piperazin-1-yl)methyl]-5-methylbenzo[d]oxazole (wb5c) and synthesized from 5-chloro-2- aminophenol and substituted phenols via condensation, chloration, amination, Williamson ether synthesis and substitution etc. All the target compounds were identified by ESI-MS, IR, 1H NMR and HRMS. Functional bioassay showed that they had moderate antagonistic activities against α1-AR, which verified our three-element pharmacophore model. In conclusion, 5-chloro-2-(4-(aryloxyalkyl)piperazin-1-yl)benzo- [d]oxazole compounds were novel candidates as potential α1-AR antagonist.

Key words: benign prostatic hyperplasia, α1-adrenoceptor, antagonist, pharmacore, benzoxazole, piperazine