摘要
N6-(2-羟乙基)-腺嘌呤核苷(HEA,1)是从冬虫夏草培养物中提取的有效成分,具有明显的镇静、催眠与抗缺氧脑保护作用。本文以HEA为先导物,设计合成了N6-取代腺苷(2～10)、2-氨基-N6-取代腺苷(11～14)、N6,N9-双取代无环核苷(20～22)、N6-取代腺嘌呤(15～19)和N6-(2-羟基乙基)-8-溴腺苷(23)共23个目标化合物,经MS、1HNMR及元素分析进行了化学结构确证。药理实验结果表明:10个化合物(1、2、4、8～14)具有不同程度的镇静、催眠和抗缺氧脑保护作用。其中化合物4、8、13的活性明显高于先导物,并初步探讨了构效关系。
N6-（2-Hydroxyethyl） adenosine, HEA （1）, an active ingredient isolated from cultured mycelia of cordyceps species which is a famous traditional tonic in China, showed brain protective, sedative hypnotic activity in pharmacological tests. In order to explore novel non-benzodiazepine sedative-hypnotic agents, HEA was treated as the lead compound. Twenty three target compounds were designed and synthesized. Their chemical structures were characterized by ~H NMR, MS and elemental analysis. Pharmacological test in vivo showed that target compounds 8, 4, 13 were more active than HEA on locomotor and gasping activities of mice. Structure-activity relationships showed that the ribose moiety at N-9 position of adenine base was critical for activity
出处
《药学学报》
CAS
CSCD
北大核心
2013年第6期881-886,共6页
Acta Pharmaceutica Sinica
关键词
冬虫夏草
腺苷类似物
镇静催眠
抗缺氧脑保护
构效关系
Cordyceps
adenosine analogues
sedative-hypnotic activity
brain protective
structure-activityrelationship
