3,4-dihydro-5-ethynyl-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran | 1190270-67-7

• 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: 3,4-dihydro-5-ethynyl-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran
• 英文别名: 5-ethynyl-3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran
• CAS: 1190270-67-7
• 化学式: C₁₆H₂₀O₂
• 分子量: 244.334
• InChiKey: ZUVVHQFFCJSRLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-5-ethynyl-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran 在 copper(ll) sulfate pentahydrate 、 三氟二甲基硫醚络合物 、 chloroamine-T 、 铜 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 2.0h， 生成 3,4-dihydro-5-(3-(4-methoxyphenyl)isoxazol-5-yl)-2,2,7,8-tetramethyl-2H-1-benzopyran-6-ol
  参考文献：
  名称：

  Isoxazole substituted chromans against oxidative stress-induced neuronal damage

  摘要：

  We have previously reported that catechol-bearing regioisomers of 5-isoxazolyl-6-hydroxy-chroman display higher in vitro neuroprotective activity, compared to hybrids with other nitrogen heterocycles, but their activity is hampered by cytotoxicity at higher concentrations. In an effort to discover non-cytotoxic isoxazole substituted chromans of high neuroprotective activity, 20 new 3- and 5-substituted (chroman-5-yl)-isoxazoles and (chroman-2-yl)-isoxazoles were synthesized using the copper(I)-catalysed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. An additional aim was to further explore the effect of the isoxazole ring substituents on the neuroprotective activity. The activity of these compounds against oxidative stress-induced death (oxytosis) of neuronal HT22 cells was evaluated and interesting SARs for this group of analogues were derived. The vast majority of new chroman analogues displayed high in vitro neuroprotective activity displaying EC(50) values below 1 mu M and lacked cytotoxicity. The position of substituents on the isoxazole ring influences the activity of the regioisomers, with the 3-aryl-5-(chroman-5-yl)-isoxazoles, 17 and 18 and bis-chroman 20 displaying higher neuroprotective activity (EC(50) similar to 0.3 mu M) compared to other (chroman-5-yl) and (chroman-2-yl)-isoxazoles. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.074
• 作为产物：
  描述：

  (1-重氮基-2-氧代丙基)膦酸二甲酯 、 3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-carboxaldehyde 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以41%的产率得到3,4-dihydro-5-ethynyl-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran
  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.