摘要
目的设计合成卤代苯氧烷胺类α1 肾上腺素受体 (α1 AR)拮抗剂并研究它们的降压活性及构效关系。方法根据苯氧烷胺类化合物DDPH的代谢物设计合成 12个卤代芳氧烷胺类化合物 ,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 ,再还原胺化得目标物 ,测试了目标化合物的降压活性 ,并用WHIM描述子进行构效关系研究。结果共合成 12个目标物 ,其结构经红外、质谱、核磁共振谱确证。药理实验显示 :12个目标物均具有一定的降压活性 ,化合物 3、10有较强的降压作用 ,但降压持续时间均比DDPH短。结论提高整个分子的对称性 ,或降低分子的取代基的复杂程度 ,对延长该类药物的降压时间是有利的。
Aim To study the antihypertensive effect and quantitative structure-activity relationship(QSAR)of halophenoxylalkylamines as α 1-adrenocepter(α 1-AR)antagonist.Methods Based on the biological activity of DDPH metabolites,12 compounds of halophenoxylalkylamines were designed and prepared.The target compounds were synthesized from 2,6-dimethylphenol and their structures were confirmed by MS, 1H-NMR,IR spectra.Their antihypertensive effects were tested and the QSAR was subjected to weighted holistic invariant molecular(WHIM)descriptors.Results The test indicates that all the target compounds exhibited antihypertensive activities.Compounds 3,10 have potent antihypertensive effect but their duration time is shorter than that of DDPH.Conclusion The QSAR indicates that the antihypertensive duration time of the compounds could be prolonged by enhancement in molecular symmetry or simplification of the molecular substituents.
出处
《中国药物化学杂志》
CAS
CSCD
2005年第1期5-11,共7页
Chinese Journal of Medicinal Chemistry
基金
8 6 3计划资助项目 (2 0 0 2AA2Z3118)
