Inhibition of adenosine deaminase by novel 5:7 fused heterocycles containing the imidazo[4,5-e][1,2,4]triazepine ring system: a structure-activity relationship study.
Inhibition of adenosine deaminase by novel 5:7 fused heterocycles containing the imidazo[4,5-e][1,2,4]triazepine ring system: a structure-activity relationship study.
复制标题
含有咪唑并[4,5-e][1,2,4]三氮杂环系统的新型 5:7 稠合杂环对腺苷脱氨酶的抑制：构效关系研究。
DOI：
10.1021/jm0304257
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Hosmane,RamachandraS
中科院分区：
文献类型：
--
作者：
Reayi,Ayub;Hosmane,RamachandraS
作为探索Coformycins与腺苷脱氨酶高度紧密结合抑制特性的结构和活性关系的计划的一部分，合成了一系列含咪唑[4，5-e][1，2，4]三氮杂环体系的类似物(1a−1h)，并在体外对哺乳动物的腺苷脱氨酶进行了抑制活性的筛选。化合物1a和1b是从4-硝基咪唑开始分五步合成的，其他的是通过与适当的醇进行简单的交换反应得到的。观察到的动力学曲线和Ki值表明，目标化合物是竞争性抑制剂，与6-−的结合强度降低了9个数量级。化合物1和1在该系列中最活跃，KI的活性在12到15μM之间。
As part of a program to explore structure−activity relationships for the extremely tight binding inhibition characteristics of coformycins to adenosine deaminase, a series of analogues (1a−1h) containing the imidazo[4,5-e][1,2,4]triazepine ring system has been synthesized and screened in vitro against a mammalian adenosine deaminase for inhibitory activity. While compounds1aand1bwere synthesized in five steps starting from 4-nitroimidazole, others were derived from1athrough simple exchange reactions with the appropriate alcohols. The observed kinetics profiles andKivalues suggest that the target compounds are competitive inhibitors that bind 6−9 orders of magnitude less tightly to the enzyme. Compounds1cand1dwere the most active in the series withKi's ranging from 12 to 15 μM.