3-hydroxy-4-methyl-5-tert-butylisoxazole | 95406-69-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-hydroxy-4-methyl-5-tert-butylisoxazole
• 英文别名: 5-tert-butyl-4-methylisoxazol-3-ol；3-hydroxy-4-methyl-5-tertbutylisoxazole；5-tert-butyl-4-methyl-1,2-oxazol-3-one
• CAS: 95406-69-2
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: LMXMBGVRZMTBSW-UHFFFAOYSA-N

物化性质

• 密度：
  1.049±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-hydroxy-4-methyl-5-tert-butylisoxazole 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 、 sodium hydride 作用下， 以 四氯化碳 为溶剂， 反应 26.25h， 生成 Dimethyl 2-acetamido-2-[[5-tert-butyl-3-(diethoxyphosphorylmethoxy)-1,2-oxazol-4-yl]methyl]propanedioate
  参考文献：
  名称：

  高度选择性的羧基和膦酰基异恶唑氨基酸AMPA受体拮抗剂的合成和药理作用。

  摘要：

  （RS）-2-氨基-3-（3-羟基-5-甲基-4-异唑基）丙酸（AMPA，5）和选择性AMPA受体拮抗剂（RS）-2-氨基-3- [3-（羧基甲氧基）-5-甲基-4-异恶唑基]丙酸（AMOA，7）已被用作设计和合成多种潜在AMPA受体拮抗剂的先导。合成了两个平行的AMOA类似物系列，包含远端羧酸（化合物8b-g和11b）或膦酸（化合物9a-g，10c和11c）。使用一系列受体结合测定法以及使用大鼠皮质切片模型的体外电生理学实验，对合成的化合物进行了药理学表征。具有叔丁基取代基的两个类似物（RS）-2-氨基-3- [5-叔丁基-3-（羧基甲氧基）-4-异恶唑基] pr膦酸（ATOA，8b）和相应的膦酸类似物ATPO（9b）是每个系列中最有效和最具选择性的AMPA拮抗剂。ATOA和ATPO对皮质切片模型中AMPA引起的去极化的IC50值分别为150和28 microM，而母体化合物AMOA的IC50

  DOI：

  10.1021/jm950826p
• 作为产物：
  描述：

  特戊酰基乙酸乙酯 在 sodium hydroxide 、 盐酸羟胺 、 sodium ethanolate 作用下， 反应 6.67h， 生成 3-hydroxy-4-methyl-5-tert-butylisoxazole
  参考文献：
  名称：

  Ibotenic Acid Analogues. Synthesis, Molecular Flexibility, and in Vitro Activity of Agonists and Antagonists at Central Glutamic Acid Receptors

  摘要：

  The syntheses of (RS)-alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionic acid (9, ATPA), (alpha-RS, beta-RS)-alpha-amino-beta-methyl-3-hydroxy-5-isoxazolepropionic acid (8), (RS)-alpha-amino-3-hydroxy-5-isoxazolebutyric acid (15a), and (RS)-alpha-amino-3-hydroxy-5-isoxazolevaleric acid (15b) are described. The compounds were tested in vitro together with (RS)-alpha-amino-3-hydroxy-5-(bromomethyl)-4-isoxazolepropionic acid (ABPA) as inhibitors of the binding of radioactive-labeled (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to rat brain synaptic membranes. These data were compared with the earlier reported effects of the compounds on single neurons in the feline spinal cord obtained by microelectrophoretic techniques. The three compounds AMPA, ATPA, and ABPA are agonists at the class of receptors assumed to represent a subtype of physiological (S)-glutamic acid (Glu) receptors. Inhibition of [3H]AMPA binding by ATPA was 1 order of magnitude weaker than that of AMPA, in agreement with the relative potency of these compounds in vivo. ABPA proved to be equipotent with AMPA both as an inhibitor of AMPA binding and as a neuronal excitant. The compounds 8, 15a, and 15b have no effect as inhibitors of AMPA binding, in agreement with in vivo studies that have shown that 8 does not affect the firing of central neurons whereas 15a and 15b are antagonists at NMDA receptors, a subpopulation of excitatory receptors not affected by AMPA. Molecular mechanical calculations on AMPA, ATPA, and ABPA using the program MM2 showed that conformations of AMPA, ABPA, and especially ATPA by rotation of the amino acid side chain have energy barriers. A possible receptor-active conformation is suggested.

  DOI：

  10.1021/jm50001a022

文献信息

• Isoxazol-5(4H)-ones. X-Ray crystal structures of a 4-hydroxyisoxazol-5(4H)-one and a [4,4′-biisoxazole]-5(4H),5′(4′H)-dione formed by oxygen oxidation of 3-tert-butyl-4-methylisoxazol-5(4H)-one
  作者：Lotte Brehm、Jørgen S. Johansen、Povl Krogsgaard-Larsen

  DOI：10.1039/p19920002059

  日期：——

  (2H)-one 6 and (RS)-3-tert-butyl-4-methylisoxazol-5(4H)-one 7. During the attempts to crystallize the inseparable mixture of tautomers 6 and 7 two other compounds, (RS)-3-tert-butyl-4-hydroxy-4-methylisoxazol-5(4H)-one 8 and (RS,RS)-3,3′-di-tert-butyl-4,4′-dimethyl-[4,4′-biisoxazole]-5(4H), 5′(4H)-dione 9, were progressively formed. The structures of compounds 8 and 9 were established by X-ray analyses

  乙基的处理（RS）-2,4,4-三甲基-3-氧代戊酸酯4在碱性条件下的羟胺，得到5-叔丁基-4-甲基异恶唑-3-醇5和3-互变异构体混合物叔丁基- 4-甲基异恶唑-5（2 H）-one 6和（RS）-3-叔丁基-4-甲基异恶唑-5（4 H）-one 7。在尝试使互变异构体6和7的不可分离的混合物结晶的过程中，出现了另外两种化合物（（RS）-3-叔丁基-4-羟基-4-甲基异恶唑-5（4 H）-8和（RS，RS）-3,3'-二叔丁基-4,4'-二甲基-[4,4'-联异唑] -5（4 H），5'（4 H）-二酮9，逐渐形成。通过X射线分析确定化合物8和9的结构。提出化合物8和9是通过用氧气氧化化合物7而形成的，但是这两个氧化过程的机理尚不清楚。
• [EN] INDOLE-2,3-DIONE-3-OXIME DERIVATIVES FOR THERAPEUTIC USE<br/>[FR] DERIVES D'INDOL-2,3-DIONE-3-OXIME DESTINES A UN USAGE THERAPEUTIQUE
  申请人：NEUROSEARCH A/S

  公开号：WO1999049864A1

  公开（公告）日：1999-10-07

  (EN) The present invention relates to the use of indole-2,3-dione-3-oxime derivatives in a method of combating diseases and disorders associated with or mediated by the release of excitatory amino acids.(FR) L'invention concerne l'utilisation de dérivés d'indol-2,3-dione-3-oxime dans une méthode de lutte contre les maladies et les troubles associés à ou induits par la libération d'acides aminés excitateurs.

  (中)本发明涉及使用吲哚-2，3-二酮-3-肟衍生物在一种对抗与或介导兴奋性氨基酸释放相关的疾病和障碍的方法中。(FR)本发明涉及使用吲哚-2，3-二酮-3-肟衍生物在一种对抗与或介导兴奋性氨基酸释放相关的疾病和障碍的方法中。
• Brehm, Lotte; Madsen, Ulf; Johansen, Joergen S., Journal of the Chemical Society. Perkin transactions I, 1991, # 8, p. 2009 - 2013
  作者：Brehm, Lotte、Madsen, Ulf、Johansen, Joergen S.、Krogsgaard-Larsen, Povl

  DOI：——

  日期：——
• NOVEL INDOLE-2,3-DIONE-3-OXIME DERIVATIVES
  申请人：NEUROSEARCH A/S

  公开号：EP0869958B1

  公开（公告）日：2004-12-29
• USE OF INDOLE-2,3-DIONE-3-OXIME DERIVATIVES AS AMPA ANTAGONISTS
  申请人：NEUROSEARCH A/S

  公开号：EP1066037B1

  公开（公告）日：2004-12-29