4-(1-[(2,4-dinitro-phenyl)-hydrazono]-ethyl)-5-(2-(naphthalen-2-yl)-ethyl)-isoxazole-3-carboxylic acid | 1208102-78-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(1-[(2,4-dinitro-phenyl)-hydrazono]-ethyl)-5-(2-(naphthalen-2-yl)-ethyl)-isoxazole-3-carboxylic acid
• 英文别名: 4-[(E)-N-(2,4-dinitroanilino)-C-methylcarbonimidoyl]-5-(2-naphthalen-2-ylethyl)-1,2-oxazole-3-carboxylic acid
• CAS: 1208102-78-6
• 化学式: C₂₄H₁₉N₅O₇
• 分子量: 489.444
• InChiKey: ODOPQWPGJOURAB-AFUMVMLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  179
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(1-[(2,4-dinitro-phenyl)-hydrazono]-ethyl)-5-(2-(naphthalen-2-yl)-ethyl)-isoxazole-3-carboxylic acid ethyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以67%的产率得到4-(1-[(2,4-dinitro-phenyl)-hydrazono]-ethyl)-5-(2-(naphthalen-2-yl)-ethyl)-isoxazole-3-carboxylic acid
  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

文献信息

• Isoxazole analogues bind the System xc- transporter: Structure–activity relationship and pharmacophore model
  作者：Sarjubhai A. Patel、Trideep Rajale、Erin O’Brien、David J. Burkhart、Jared K. Nelson、Brendan Twamley、Alex Blumenfeld、Monika I. Szabon-Watola、John M. Gerdes、Richard J. Bridges、Nicholas R. Natale

  DOI：10.1016/j.bmc.2009.11.001

  日期：2010.1

  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.