3-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)-5-cyclopentyl-isoxazole | 1333118-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 3-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)-5-cyclopentyl-isoxazole
• CAS: 1333118-48-1
• 化学式: C₂₂H₂₉NO₃
• 分子量: 355.477
• InChiKey: LJDJIPMIZLZXDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.51
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  44.49
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)-5-cyclopentyl-isoxazole 在 三氟二甲基硫醚络合物 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以64%的产率得到3,4-dihydro-2,5,7,8-tetramethyl-2-[5-(cyclopentyl)-3-isoxazolyl]-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：

  (6-methoxy-2,5,7,8-tetramethylchroman-2-yl)methanol 在 吡啶 、 copper(ll) sulfate pentahydrate 、 盐酸羟胺 、 chloroamine-T 、 铜 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 生成 3-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)-5-cyclopentyl-isoxazole
  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