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化学学报
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化学学报 ›› 2002, Vol. 60 ›› Issue (4): 725-731. 上一篇    下一篇

研究论文

N-（取代苯基哌嗪基烷基）酰胺类α_1-受体拮抗剂的设计、合成及生物活性研究

方浩;夏霖;江振洲;张伟;张陆勇   

  1. 中国药科大学药物化学教研室,南京(210009)
  • 发布日期:2002-04-15

Design, Synthesis and Biological Activity Study on N-[4- (Substituted Phenyl)piperazine-1-yl]alkyl Amide Series as α_1- Adrenoceptor Antagonists

Fang Hao;Xia Lin;Jiang Zhenzhou;Zhang Wei;Zhang Luyong   

  1. Department of Medicinal Chemistry, Xingzhong New Drug Research and Development Center, China Pharmaceutical University,Nanjing(210009)
  • Published:2002-04-15

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被引次数

1

结合苯基哌基类α_1-受体拮抗剂的构效关系和我们应用计算机辅助药物设计 方法所构建的药效团模型，设计并合成了呋喃-2-甲酸{ω-[4-（取代苯基）-1-哌 嗪基]-烷基}酰胺和2-氧代-2H-苯并吡喃-3-羧酸{ω-[4-（取代苯基）-1-哌嗪基]- 烷基}酰胺两类衍生物，其结构经~1H NMR，IR及MS（HRMS）确证。初步生物活性测 试表明，所合成的目标化合物多数具有较好的α_1-受体拮抗剂，良性前列腺增生 。

关键词: 哌嗪 P, 拮抗剂, 构效关系, 计算机辅助设计, 呋喃 P, 甲酸 P, 酰胺 P, 苯并吡喃 P, 生物活性

Novel furan-2-carboxylic acid {ω-[4-(substituted phenyl)- piperazine-1-yl]alkyl} amide and 2-oxo-2H-chromene-3-carboxylic acid {ω -[4-(substituted phenyl)-piperazine-1-yl]alkyl} amide derivatives have been designed and synthesized based on the structure and acitivity relationship (SAR) of phenylpiperazine series as α_1-adrenoceptor (α _1-AR) antagonists and the results of computer-aided drug design we studied before. All the target compounds have been identified by ~1H NMR, IR and MS (HRMS). Preliminary bioassay suggests that most of the target compounds display good blocking activity to α_1-AR. The potency (pA_2) of compound 3b is higher than prazosin.

Key words: PIPERAZINE P, ANTAGONIST, STRUCTURE ACTIVITY RELATIONSHIP, COMPUTER AIDED DESIGN, FURAN P, FORMIC ACID P, AMIDES P, BENZOPYRAN P, BIOLOGICAL ACTIVITY

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