ethyl 5-benzyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate | 1340474-39-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 5-benzyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate
• CAS: 1340474-39-6
• 化学式: C₂₀H₂₅NO₅
• 分子量: 359.422
• InChiKey: UCJXJVIPMCUPJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 5-benzyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate 在 对甲苯磺酸 、 sodium hydroxide 作用下， 以 丙酮 为溶剂， 生成 5-benzyl-4-(1-(2-(3,5-bis(trifluoromethyl)phenyl)hydrazono)ethyl)isoxazole-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-isoxazolecarboxylic acid 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 在 N-溴代丁二酰亚胺(NBS) 、 palladium diacetate 、 potassium carbonate 、 2-(二叔丁基膦)联苯 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.34h， 生成 ethyl 5-benzyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate
  参考文献：
  名称：

  微波条件下苄基溴化物的 Suzuki-Miyaura 交叉偶联

  摘要：

  已经开发了一种在微波条件下用于苄基 Suzuki-Miyaura 交叉偶联的程序。这些条件允许杂环化合物偶联。发现的最佳条件是 Pd(OAc) 2，JohnPhos 作为催化剂和配体，碳酸钾作为碱，DMF 作为溶剂。使用这些条件，合成了结构多样的化合物库。

  DOI：

  10.1016/j.tetlet.2011.08.096

文献信息

• Suzuki–Miyaura cross-coupling of benzylic bromides under microwave conditions
  作者：Steven W. McDaniel、Charles M. Keyari、Kevin C. Rider、Nicholas R. Natale、Philippe Diaz

  DOI：10.1016/j.tetlet.2011.08.096

  日期：2011.10

  A procedure for benzylic Suzuki–Miyaura cross-coupling under microwave conditions has been developed. These conditions allowed for heterocyclic compounds to be coupled. Optimum conditions found were Pd(OAc)2, JohnPhos as the catalyst and ligand, potassium carbonate as the base, and DMF as the solvent. Using these conditions, a library of structurally diverse compounds was synthesized.

  已经开发了一种在微波条件下用于苄基 Suzuki-Miyaura 交叉偶联的程序。这些条件允许杂环化合物偶联。发现的最佳条件是 Pd(OAc) 2，JohnPhos 作为催化剂和配体，碳酸钾作为碱，DMF 作为溶剂。使用这些条件，合成了结构多样的化合物库。
• Novel di-aryl-substituted isoxazoles act as noncompetitive inhibitors of the system <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif" overflow="scroll"><mml:mrow><mml:msubsup><mml:mrow><mml:mtext>x</mml:mtext></mml:mrow><mml:mrow><mml:mtext>c</mml:mtext></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:mrow></mml:math> cystine/glutamate exchanger
  作者：J.L. Newell、C.M. Keyari、S.W. McDaniel、P.J. Diaz、N.R. Natale、S.A. Patel、R.J. Bridges

  DOI：10.1016/j.neuint.2013.11.012

  日期：2014.7

  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.