双环/三环氮杂糖稠合噻嗪烷-4-酮的合成及其对HIV逆转录酶的抑制活性。
Synthesis of bi-/tricyclic azasugars fused thiazinan-4-one and their HIV-RT inhibitory activity.
作者信息
Chen Hua, Hao Le, Zhu Mo, Yang Tianyu, Wei Sinan, Qin Zhanbin, Zhang Pingzhu, Li Xiaoliu
机构信息
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
出版信息
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3426-9. doi: 10.1016/j.bmcl.2014.05.079. Epub 2014 Jun 2.
Novel bi-/tricyclic azasugars fused thiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. The aryl group (phenyl or pyridyl) in mercaptan acid had an important effect on the formation of the diastereomers of the tricyclic hybrids 12b-15b. The new bi/tricyclic azasugars 3a-8a, 4b, 6b, 8b and the known ones 2a, 2b were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that compounds 2a-b, 4a, 4b, 5a, and 6a could effectively inhibit RT activity. Among them, the tricyclic azasugar 5a was the best one with the IC50 value of 0.49 μM. Structure-activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was benefit for their anti-HIV RT activity.
通过微波辐射下的串联施陶丁格/氮杂维蒂希/环化反应，方便地合成了新型双环/三环氮杂糖稠合噻嗪烷-4-酮。硫醇酸中的芳基（苯基或吡啶基）对三环杂化物12b - 15b非对映异构体的形成有重要影响。对新型双环/三环氮杂糖3a - 8a、4b、6b、8b以及已知的2a、2b进行了HIV逆转录酶（RT）抑制活性检测。结果表明，化合物2a - b、4a、4b、5a和6a能有效抑制RT活性。其中，三环氮杂糖5a是最佳的，IC50值为0.49 μM。构效关系分析表明，三环氮杂糖中的苯基有利于其抗HIV RT活性。
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