尼苯坦及其类似物的合成与抗纤颤活性

Synthesis and antifibrillatory activity of nibentan and its analogues.

作者信息

Davydova N K, Sizova O S, Vinogradova S M, L'vov A I, Glushkov R G, Yuzhakov S D, Mashkovskiy M D

机构信息

Department of Organic Synthesis, Centre of Chemistry of Drugs, Zubovskaya Str. 7, Moscow, Russia.

出版信息

Eur J Med Chem. 2000 Feb;35(2):205-15. doi: 10.1016/s0223-5234(00)00116-1.

DOI:10.1016/s0223-5234(00)00116-1

PMID:10758282

Abstract

A series of 1,5-diaminopentane derivatives, structurally related to nibentan, was synthesized and tested for antifibrillatory activity. Improved modifications of some known chemical syntheses were proposed. (+/-)-N-[5-(Diethylamino)-1-(4-nitrophenyl)pentyl]-benzamide hydrochloride, (+/-)-N-[5-(diethylamino)-1-(4-nitrophenyl)pentyl]-4-nitrobenzamide hydrochloride and (+/-)-N-[5-(diethylamino)-1-(4-hydroxyphenyl)pentyl]-4-nitrobenzamide hydrochloride were more potent than nibentan and possessed a longer duration of action (up to 5 h in comparison with 60-90 min for nibentan). The antifibrillatory activity of (+/-)-N-[5-(diethylamino)-1-(4-methoxyphenyl)pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-sotalol and sematilide.

摘要

合成了一系列与尼苯坦结构相关的1,5 - 二氨基戊烷衍生物，并对其抗纤颤活性进行了测试。提出了对一些已知化学合成方法的改进。（±）-N-[5-（二乙氨基）-1-（4-硝基苯基）戊基]-苯甲酰胺盐酸盐、（±）-N-[5-（二乙氨基）-1-（4-硝基苯基）戊基]-4-硝基苯甲酰胺盐酸盐和（±）-N-[5-（二乙氨基）-1-（4-羟基苯基）戊基]-4-硝基苯甲酰胺盐酸盐比尼苯坦更有效，且作用持续时间更长（与尼苯坦的60 - 90分钟相比长达5小时）。（±）-N-[5-（二乙氨基）-1-（4-甲氧基苯基）戊基]-4-硝基苯甲酰胺盐酸盐的抗纤颤活性与尼苯坦相当，但超过了D-索他洛尔和塞马利德的效力。