5-{[(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methoxy]methyl}-3-(4-hydroxyphenyl)isoxazole | 1333118-63-0

• 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: 5-{[(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methoxy]methyl}-3-(4-hydroxyphenyl)isoxazole
• 英文别名: 4-[5-[(6-Methoxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methoxymethyl]-1,2-oxazol-3-yl]phenol；4-[5-[(6-methoxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methoxymethyl]-1,2-oxazol-3-yl]phenol
• CAS: 1333118-63-0
• 化学式: C₂₅H₂₉NO₅
• 分子量: 423.509
• InChiKey: DSNORUJKNRVIGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2-(prop-2-ynyloxymethyl)-2H-1-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 2-{[(3-(4-methoxyphenyl)isoxazol-5-yl)methoxy]methyl}-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol 、 5-{[(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methoxy]methyl}-3-(4-hydroxyphenyl)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

文献信息

• Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity
  作者：Maria Koufaki、Theano Fotopoulou、Marianna Kapetanou、Georgios A. Heropoulos、Efstathios S. Gonos、Niki Chondrogianni

  DOI：10.1016/j.ejmech.2014.06.046

  日期：2014.8

  One-pot uncatalysed microwave-assisted 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxides and alkynes bearing protected antioxidant substituents, were regioselectively afforded 3,5-disubstituted isoxazoles. The yields were moderate, based on the starting aldehydes, while the reaction times were in general shorter than those reported in the literature. The cytoprotective and anti-ageing effect of the final deprotected compounds was evaluated in vitro, on cellular survival following oxidative challenge and in vivo, on organismal longevity using the nematode Caenorhabditis elegans. The activity of the isoxazole analogues depends on the nature and the number of the antioxidant substituents. Analogue 17 bearing a phenolic group and a 6-OH-chroman group is a promising anti-ageing agent, since it increased survival of human primary fibroblasts following treatment with H2O2 and extended C. elegans lifespan.
• Isoxazole substituted chromans against oxidative stress-induced neuronal damage
  作者：Maria Koufaki、Alexandra Tsatsaroni、Xanthippi Alexi、Helène Guerrand、Sofia Zerva、Michael N. Alexis

  DOI：10.1016/j.bmc.2011.06.074

  日期：2011.8

  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.