药学学报, 2013, 48(6): 881-886
引用本文:
王冬梅, 刘晓辉, 郭 辉, 黄俊华, 王 琳. 腺苷类似物的设计、合成及活性研究[J]. 药学学报, 2013, 48(6): 881-886.
WANG Dong-mei, LIU Xiao-hui, GUO Hui, HUANG Jun-hua, WANG Lin. Design, synthesis and biological activity evaluation of adenosine analogues[J]. Acta Pharmaceutica Sinica, 2013, 48(6): 881-886.

腺苷类似物的设计、合成及活性研究
王冬梅, 刘晓辉, 郭 辉, 黄俊华*, 王 琳*
(中国医学科学院、北京协和医学院药物研究所, 北京 100050)
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 (210)2-氨基-N6-取代腺苷 (1114)N6, N9-双取代无环核苷 (2022)N6-取代腺嘌呤 (1519) N6-(2-羟基乙基)-8-溴腺苷 (23) 23个目标化合物, MS1H NMR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 (124814) 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4813的活性明显高于先导物, 并初步探讨了构效关系。

关键词:   
Design, synthesis and biological activity evaluation of adenosine analogues
Abstract:

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 1H 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.

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