(R)-1-(9-(6-(tert-butyldimethylsilanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonyl)-1H-1,2,3-triazole | 1071461-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (R)-1-(9-(6-(tert-butyldimethylsilanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonyl)-1H-1,2,3-triazole
• 英文别名: (R)-1-(9-(6-(tert-butyldimethylsilyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonyl)-1H-1,2,3-triazole；tert-butyl-dimethyl-[[(2R)-2,5,7,8-tetramethyl-2-[9-(triazol-1-yl)nonyl]-3,4-dihydrochromen-6-yl]oxy]silane
• CAS: 1071461-15-8
• 化学式: C₃₀H₅₁N₃O₂Si
• 分子量: 513.839
• InChiKey: QERWXCLRHMEIBU-SSEXGKCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.49
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  49.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-(9-(6-(tert-butyldimethylsilanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonyl)-1H-1,2,3-triazole 在 四丁基氟化铵 、 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以70%的产率得到(R)-2-(9-(1H-1,2,3-triazol-1-yl)nonyl)-2,5,7,8-tetramethylchroman-6-ol
  参考文献：
  名称：

  Tocopherol derivatives and uses thereof

  摘要：

  提供具有一般公式的生育酚衍生物：其中n是6到13的整数，R1是氢，硅醚或醋酸酯，R2是一个可选择地取代的含氮杂环或多环含氮杂环；以及其药用可接受的盐。还提供了一种合成这些化合物的方法。这些生育酚衍生物能够抑制生育酚和生育三烯酚（维生素E化合物）的代谢的主要酶，即生育酚-ω-羟基化酶，从而增加这些化合物在血浆和组织中的含量并延长其可用性。

  公开号：

  US20080293792A1
• 作为产物：
  描述：

  9-((2R)-6-{[tert-butyl(dimethyl)-silyl]-oxy}-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-yl)-1-nonanol 在 4-二甲氨基吡啶 18-冠醚-6 、 potassium tert-butylate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 16.75h， 生成 (R)-1-(9-(6-(tert-butyldimethylsilanyloxy)-2,5,7,8-tetramethylchroman-2-yl)nonyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  Tocopherol derivatives and uses thereof

  摘要：

  提供具有一般公式的生育酚衍生物：其中n是6到13的整数，R1是氢，硅醚或醋酸酯，R2是一个可选择地取代的含氮杂环或多环含氮杂环；以及其药用可接受的盐。还提供了一种合成这些化合物的方法。这些生育酚衍生物能够抑制生育酚和生育三烯酚（维生素E化合物）的代谢的主要酶，即生育酚-ω-羟基化酶，从而增加这些化合物在血浆和组织中的含量并延长其可用性。

  公开号：

  US20080293792A1

文献信息

• Tocopherol derivatives and uses thereof
  申请人：Atkinson Jeffrey

  公开号：US20080293792A1

  公开（公告）日：2008-11-27

  Tocopherol derivatives having the general formula: wherein n is an integer of 6 to 13, R 1 is hydrogen, a silyl ether or acetate, R 2 is an optionally substituted nitrogen-containing heterocycle or a polycyclic nitrogen-containing heterocycle; and pharmaceutically acceptable salts thereof are provided. A method for synthesizing the compounds is also provided. The tocopherol derivatives are capable of inhibiting the primary enzyme responsible for the metabolism of the tocopherols and tocotrienols compounds of vitamin E, namely tocopherol-ω-hydroxylase, and thus increase the amount and prolong the availability of these compounds in plasma and tissue.

  提供具有一般公式的生育酚衍生物：其中n是6到13的整数，R1是氢，硅醚或醋酸酯，R2是一个可选择地取代的含氮杂环或多环含氮杂环；以及其药用可接受的盐。还提供了一种合成这些化合物的方法。这些生育酚衍生物能够抑制生育酚和生育三烯酚（维生素E化合物）的代谢的主要酶，即生育酚-ω-羟基化酶，从而增加这些化合物在血浆和组织中的含量并延长其可用性。
• Inhibition of oxidative metabolism of tocopherols with ω-N-heterocyclic derivatives of vitamin E
  作者：Stephan Ohnmacht、Phillip Nava、Ryan West、Robert Parker、Jeffrey Atkinson

  DOI：10.1016/j.bmc.2008.07.020

  日期：2008.8

  The oxidative metabolism of tocopherols and tocotrienols by monooxygenases is a key factor in the plasma and tissue clearance of forms of vitamin E other than alpha-tocopherol. It is well known that a commonly ingested form of vitamin E, gamma-tocopherol, has greatly reduced plasma half-life (faster clearance) than alpha-tocopherol. The tocotrienols are metabolized even faster than gamma-tocopherol. Both gamma-tocopherol and alpha- and delta-tocotrienol possess intriguing biological activities that are different from alpha-tocopherol, making them potentially of interest for therapeutic use. Unfortunately, the fast clearance of non-alpha-tocopherols from animal tissues is a significant hurdle to maximizing their effect(s) as dietary supplements. We report here the design and synthesis of N-heterocycle-containing analogues of alpha-tocopherol that act as inhibitors of Cyp4F2, the key monooxygenase responsible for omega-hydroxylation of the side chain of tocols. In particular, an omega-imidazole containing compound, 1, [(R)-2-(9-(1H-imidazol-1-yl)nonyl)-2,5,7,8-tetramethylchroman-6-ol] had an ED50 for inhibition of gamma-CEHC production from c-tocopherol of similar to 1 nM when tested in HepG2 cells in culture. Furthermore, feeding of 1 to mice along with rapidly metabolized delta-tocopherol, resulted in a doubling of the delta-tocopherol/alpha-tocopherol ratio in liver ( P<0.05). Thus, 1 may be a useful adjuvant to the therapeutic use of non-alpha-tocopherols. (C) 2008 Elsevier Ltd. All rights reserved.