ethyl 5-((naphthalen-2-ylmethoxy)methyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate | 1208103-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 5-((naphthalen-2-ylmethoxy)methyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate
• CAS: 1208103-03-0
• 化学式: C₂₅H₂₉NO₆
• 分子量: 439.508
• InChiKey: DKOKZSQGPWQAIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  80.02
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 5-((naphthalen-2-ylmethoxy)methyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate 在 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 以72%的产率得到ethyl 4-acetyl-5-((naphthalen-2-ylmethoxy)methyl)isoxazole-3-carboxylate
  参考文献：
  名称：

  Isoxazole analogues bind the System xc- transporter: Structure–activity relationship and pharmacophore model

  摘要：

  Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System x(c)(-). Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System x(c)(-), the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y = Y' = 3,5-(CF3)(2), which both inhibited glutamate uptake by the System x(c)(-) transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.001
• 作为产物：
  描述：

  ethyl 5-(hydroxymethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.08h， 以69%的产率得到ethyl 5-((naphthalen-2-ylmethoxy)methyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate
  参考文献：
  名称：

  Isoxazole analogues bind the System xc- transporter: Structure–activity relationship and pharmacophore model

  摘要：

  Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System x(c)(-). Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System x(c)(-), the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y = Y' = 3,5-(CF3)(2), which both inhibited glutamate uptake by the System x(c)(-) transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.001