2,4-二甲氧基苯乙胺类α_1-肾上腺素受体拮抗剂的合成、生物活性研究  

Synthesis and biological activity of 2,4-dimethoxyphenylethylamines as α_1-AR antagonist

作　　者：习保民[1] 江振洲[2] 王涛[2] 倪沛洲[3] 

机构地区：[1]南方医科大学药学院药物化学系,广东广州510515 [2]中国药科大学国家新药筛选中心,江苏南京210038 [3]中国药科大学有机化学教研室,江苏南京210009

出　　处：《中国药物化学杂志》2008年第6期401-405,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30600776);国家高技术研究发展计划项目(863项目;2002AA2Z3118)

摘　　要：目的设计合成苯乙胺类α1-肾上腺素受体(α1-AR)拮抗剂,并研究它们对大鼠肛尾肌收缩功能的影响。方法以DDPH为先导化合物设计合成了11个新化合物,以2,6-二甲基苯酚为原料经多步反应得中间体卤代苯氧丙酮,再经还原胺化得目标物。运用大鼠肛尾肌收缩功能实验测定目标物的拮抗活性。结果共合成了11个目的物,其结构经IR、HRMS1、H-NMR确证。结论生物活性测试显示大部分目标化合物均具有一定的α1-AR拮抗活性,化合物Ⅲk拮抗作用和DDPH接近。Aim To study the blocking activity of 2, 4-dimethoxyphenylethylamine analogues as α1-adrenocepter（α1-AR） antagonist. Methods Based on the biological activity of DDPH, 11 analogues of 2, 4- dimethoxyphylethylamines were designed and prepared. The target compounds were synthesized from 2, 6- dimetbylphenol. Their structures were confirmed by HRMS, ^1H-NMR, IR spectra. Their bioaetivities were also tested. Results The result indicated that most the target compounds exhibited well in blocking α1- adrenoceptor. Conclusion The preliminary bioassay indicates that compound Ⅲ k functions well in blocking α1-adrenoceptor.

关 键 词：化学合成 α1-AR拮抗剂 DDPH 

分 类 号：R914[医药卫生—药物化学]