摘要
哌嗪环是药物结构修饰中常用的一类重要氮杂环,在以DNA拓扑异构酶、羊毛甾醇14α-去甲基化酶、(1,3)-β-D-葡聚糖合成酶、11β-羟基固醇脱氢酶1、葡萄糖激酶、β-分泌酶和脂肪酰胺水解酶等为靶点的化合物中引入哌嗪环,不仅可以增强药物疗效,改善药物的药代动力学性质,而且易被其他官能团修饰,构成多药理靶点的杂合体,呈现出广泛的生物活性,可用于治疗细菌感染、真菌感染、2型糖尿病、阿尔茨海默病以及疼痛等,具有很大的开发价值。本文综述了作用于酶的含哌嗪化合物在抗菌、抗真菌、抗糖尿病、治疗阿尔茨海默病与镇痛等方面的最新进展及其构效关系。
Piperazine ring is an important class of heteroeyclic nitrogen which is widely used in structural modification of drugs. The introduction of piperazine ring into compounds, which are targeting DNA topoisomerase, lansterol 14a-demethy- lase, （ 1,3 ） -β-D-glucan synthase, 11 β -hydroxy steroid dehydrogenase 1, glucokinase, beta-site APP cleaving enzyme 1 and fatty acid amide hydrolase, not only could enhance their efficacy and improve pharmaeokinetic properties, but also could be easy to be modified to constitute a hybrid with multi pharmacological targets. These compounds have shown a wide range of biological activities and could be used for the treatment of bacterial infection, fungal infection, type 2 diabetes, Alzheimer＇s disease and pain, which have great development value. Therefore, the recent advances of the piperazine-containing com- pounds as antibacterial agents, antifungal agents, anti-diabetes agents, anti-Alzheimer＇s disease agents and anodyne were de- scribed, and their structure-activity relationship were also reviewed.
出处
《世界科技研究与发展》
CSCD
2017年第2期149-158,共10页
World Sci-Tech R&D
基金
重庆市科技项目(cstc2016jcyj A0437)
重庆医药高等专科学校科研项目(ygz2013108)资助
