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

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

结合苯基哌嗪类α1 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1HNMR ,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α1 受体拮抗活性 .其中一个目标化合物 3b的活性 (pA2 )高于阳性对照药哌唑嗪 .

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.