N'-hydroxy-2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl) acetamidine | 1190270-32-6

• 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: N'-hydroxy-2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl) acetamidine
• CAS: 1190270-32-6
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: RQFUNUJNZQFLJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  77.07
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N'-hydroxy-2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl) acetamidine 、 Thioctic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以63%的产率得到N'-(5-(1,2-dithiolan-3-yl)pentanoyloxy)-2-(6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl) acetamidine
  参考文献：
  名称：

  Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids

  摘要：

  Novel 1,2-dithiolane/chroman hybrids bearing heterocyclic rings such as 1,2,4- and 1,3,4-oxadiazole, 1,2,3-triazole and tetrazole were designed and synthesized. The neuroprotective activity of the new analogues was tested against oxidative stress-induced cell death of glutamate-challenged HT22 hippocampal neurons. Our results show that bioisosteric replacement of amide group in 2-position of the chroman moiety, by 1,3,4- oxadiazole did not affect activity. However, analogue 5 bearing the 1,2,4- oxadiazole moiety showed improved neuroprotective activity. The presence of nitrogen heterocycles strongly influences the neuroprotective activity of 5-substituted chroman derivatives, depending on the nature of heterocycle. Replacement of the amide group of the first generation analogues by 1,2,4- oxadiazole or 1,2,3-triazole resulted in significant improvement of the activity against glutamate induced oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.010
• 作为产物：
  描述：

  2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl)acetonitrile 在 盐酸羟胺 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以66%的产率得到N'-hydroxy-2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-yl) acetamidine
  参考文献：
  名称：

  Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids

  摘要：

  Novel 1,2-dithiolane/chroman hybrids bearing heterocyclic rings such as 1,2,4- and 1,3,4-oxadiazole, 1,2,3-triazole and tetrazole were designed and synthesized. The neuroprotective activity of the new analogues was tested against oxidative stress-induced cell death of glutamate-challenged HT22 hippocampal neurons. Our results show that bioisosteric replacement of amide group in 2-position of the chroman moiety, by 1,3,4- oxadiazole did not affect activity. However, analogue 5 bearing the 1,2,4- oxadiazole moiety showed improved neuroprotective activity. The presence of nitrogen heterocycles strongly influences the neuroprotective activity of 5-substituted chroman derivatives, depending on the nature of heterocycle. Replacement of the amide group of the first generation analogues by 1,2,4- oxadiazole or 1,2,3-triazole resulted in significant improvement of the activity against glutamate induced oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.010

文献信息

• Synthesis of a second generation chroman/catechol hybrids and evaluation of their activity in protecting neuronal cells from oxidative stress-induced cell death
  作者：Maria Koufaki、Elissavet Theodorou、Xanthippi Alexi、Michael N. Alexis

  DOI：10.1016/j.bmc.2010.04.042

  日期：2010.6.1

  A new generation of chroman/catechol hybrids bearing heterocyclic five-membered rings, such as 1,2, 4-oxadiazole 1,3,4-oxadiazole, 1,2,3-triazole, tetrazole and isoxazole, were designed and synthesized. The activity of the new derivatives against oxidative stress induced neuronal damage, was evaluated using glutamate-challenged hippocampal HT22 cells.Compound 3 in which a 3,4-dimethoxyphenyl moiety, is directly attached to the 1,2,4-oxadiazole ring was the most active among the 2-substituted chroman analogues, with EC50 = 254 +/- 65 nM. Concerning the 5-subtituted chroman analogues, isoxazole derivative 29 exhibited the strongest activity (EC50 = 245 +/- 38 nM). However, 29 was cytotoxic at concentrations higher than 1 mu M, while the triazole analogue 24 (EC50 = 801 +/- 229 nM), was non-toxic at all concentrations tested. (C) 2010 Elsevier Ltd. All rights reserved.