ethyl 4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazineylidene)ethyl)-5-methylisoxazole-3-carboxylate | 1208102-87-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazineylidene)ethyl)-5-methylisoxazole-3-carboxylate
• CAS: 1208102-87-7
• 化学式: C₁₇H₁₅F₆N₃O₃
• 分子量: 423.315
• InChiKey: HISJZMRABJOTFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  76.72
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazineylidene)ethyl)-5-methylisoxazole-3-carboxylate 在 sodium hydroxide 作用下， 生成 4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazono)ethyl)-5-methylisoxazole-3-carboxylic acid
  参考文献：
  名称：

  Novel di-aryl-substituted isoxazoles act as noncompetitive inhibitors of the system xc- cystine/glutamate exchanger

  摘要：

  The system x(c)(-) antiporter is a plasma membrane transporter that mediates the exchange of extracellular L-cystine with intracellular L-glutamate. This exchange is significant within the context of the CNS because the import of L-cystine is required for the synthesis of the antioxidant glutathione, while the efflux of L-glutamate has the potential to contribute to either excitatory signaling or excitotoxic pathology. Changes in the activity of the transport system have been linked to the underlying pathological mechanisms of a variety of CNS disorders, one of the most prominent of which is its highly enriched expression in glial brain tumors. In an effort to produce more potent system x(c)(-) blockers, we have been using amino-3-carboxy-5-methylisoxazole propionic acid (ACPA) as a scaffold for inhibitor development. We previously demonstrated that the addition of lipophilic aryl groups to either the #4 or #5 position on the isoxazole ring markedly increased the inhibitory activity at system x(c)(-). In the present work a novel series of analogues has been prepared in which aryl groups have been introduced at both the #4 and #5 positions. In contrast to the competitive action of the mono-substituted analogues, kinetic analyses indicate that the di-substituted isoxazoles block system x(c)(-)-mediated uptake of H-3-L-glutamate into SNB-19 cells by a noncompetitive mechanism. These new analogues appear to be the first noncompetitive inhibitors identified for this transport system, as well as being among the most potent blockers identified to date. These dialyl-isoxazoles should be of value in assessing the physiological roles and molecular pharmacology of system x(c)(-). (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.neuint.2013.11.012
• 作为产物：
  描述：

  3,5-双(三氟甲基)苯肼 、 3-isoxazolecarboxylic acid 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 在 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 生成 ethyl 4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazineylidene)ethyl)-5-methylisoxazole-3-carboxylate
  参考文献：
  名称：

  Novel di-aryl-substituted isoxazoles act as noncompetitive inhibitors of the system xc- cystine/glutamate exchanger

  摘要：

  The system x(c)(-) antiporter is a plasma membrane transporter that mediates the exchange of extracellular L-cystine with intracellular L-glutamate. This exchange is significant within the context of the CNS because the import of L-cystine is required for the synthesis of the antioxidant glutathione, while the efflux of L-glutamate has the potential to contribute to either excitatory signaling or excitotoxic pathology. Changes in the activity of the transport system have been linked to the underlying pathological mechanisms of a variety of CNS disorders, one of the most prominent of which is its highly enriched expression in glial brain tumors. In an effort to produce more potent system x(c)(-) blockers, we have been using amino-3-carboxy-5-methylisoxazole propionic acid (ACPA) as a scaffold for inhibitor development. We previously demonstrated that the addition of lipophilic aryl groups to either the #4 or #5 position on the isoxazole ring markedly increased the inhibitory activity at system x(c)(-). In the present work a novel series of analogues has been prepared in which aryl groups have been introduced at both the #4 and #5 positions. In contrast to the competitive action of the mono-substituted analogues, kinetic analyses indicate that the di-substituted isoxazoles block system x(c)(-)-mediated uptake of H-3-L-glutamate into SNB-19 cells by a noncompetitive mechanism. These new analogues appear to be the first noncompetitive inhibitors identified for this transport system, as well as being among the most potent blockers identified to date. These dialyl-isoxazoles should be of value in assessing the physiological roles and molecular pharmacology of system x(c)(-). (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.neuint.2013.11.012