4-[(2S',6S')-6'-(4-((6-aminohexyl)oxy)butyl)tetrahydropyran-2-yl]-1-[(2S'',6S'')-6''-(4-hydroxybutyltetrahydropyran-2-yl)methyl]-1H-1,2,3-triazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(2S',6S')-6'-(4-((6-aminohexyl)oxy)butyl)tetrahydropyran-2-yl]-1-[(2S'',6S'')-6''-(4-hydroxybutyltetrahydropyran-2-yl)methyl]-1H-1,2,3-triazole
• 英文别名: 6-[4-[(2S,6S)-6-[[4-[(2S,6S)-6-(4-phenylmethoxybutyl)oxan-2-yl]triazol-1-yl]methyl]oxan-2-yl]butoxy]hexan-1-amine
• 化学式: C₃₄H₅₆N₄O₄
• 分子量: 584.843
• InChiKey: VFPSWMSJSCTFEO-SUGCFTRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  42
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  93.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  糠酸（呋喃甲酸） 、 4-[(2S',6S')-6'-(4-((6-aminohexyl)oxy)butyl)tetrahydropyran-2-yl]-1-[(2S'',6S'')-6''-(4-hydroxybutyltetrahydropyran-2-yl)methyl]-1H-1,2,3-triazole 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以69%的产率得到N-(6-(4-((2S,6S)-6-((4-((2S,6S)-6-(4-(benzyloxy)butyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-2-yl)butoxy)hexyl)furan-2-carboxamide
  参考文献：
  名称：

  Simplifying nature: Towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

  摘要：

  The need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the world's very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product. Analogues were active against T. brucei, with a nitrofuran compound displaying nanomolar trypanocidal activity. Several analogues also showed strong activity against T. cruzi and L. major. Importantly, select compounds gave excellent selectivity over mammalian cells with a furan-based analogue highly selective while remaining active against all three cell lines, thus representing a potential lead for a new broad spectrum kinetoplastid inhibitor. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.021
• 作为产物：
  描述：

  5-hexenyl methanesulfonate 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 偶氮二甲酸二异丙酯 、 Co(salen^t-Bu,^t-Bu)Cl 、 camphor-10-sulfonic acid 、 碘 、 sodium hydride 、 magnesium 、 溶剂黄146 、 sodium ascorbate 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 、 叔丁醇 为溶剂， 反应 90.92h， 生成 4-[(2S',6S')-6'-(4-((6-aminohexyl)oxy)butyl)tetrahydropyran-2-yl]-1-[(2S'',6S'')-6''-(4-hydroxybutyltetrahydropyran-2-yl)methyl]-1H-1,2,3-triazole
  参考文献：
  名称：

  Simplifying nature: Towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

  摘要：

  The need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the world's very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product. Analogues were active against T. brucei, with a nitrofuran compound displaying nanomolar trypanocidal activity. Several analogues also showed strong activity against T. cruzi and L. major. Importantly, select compounds gave excellent selectivity over mammalian cells with a furan-based analogue highly selective while remaining active against all three cell lines, thus representing a potential lead for a new broad spectrum kinetoplastid inhibitor. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.021