3-甲氧基-4-甲基-5-(2-甲基-2-丙基)-1,2-恶唑 | 95406-70-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-甲氧基-4-甲基-5-(2-甲基-2-丙基)-1,2-恶唑
• 英文名称: 3-methoxy-4-methyl-5-tert-butylisoxazole
• 英文别名: 5-tert-butyl-3-methoxy-4-methylisoxazole；5-(tert-Butyl)-3-methoxy-4-methylisoxazole；5-tert-butyl-3-methoxy-4-methyl-1,2-oxazole
• CAS: 95406-70-5
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: IXDLHHCPSWDHFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-甲氧基-4-甲基-5-(2-甲基-2-丙基)-1,2-恶唑 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 、 水 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 20.0h， 生成 5-tert-butyl-3-methoxyisoxazole-4-carbaldehyde
  参考文献：
  名称：

  Synthesis and Structure-Activity Studies on Acidic Amino Acids and Related Diacids as NMDA Receptor Ligands

  摘要：

  The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively, of(S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [H-3]CPP-binding assay (IC50 = 7 +/- 3 mu M) and electropharmacologically in the rat cortical wedge model (EC(50) = 8 +/- 2 mu M) In contrast to this, the tert-butyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a c were studied by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very weak basic character, 6 is a, perhaps subtype-selective, NMDA receptor agonist and a potent neurotoxic agent. These aspects prompted us to synthesize and test the diacids 8a,b, in which the amino group of AMAA, has been replaced by a methylthio and methoxy group, respectively. Neither compound showed significant affinity for nor depolarizing effects at NMDA receptors. The hydroxymethyl AMPA analogue 3c showed no interaction with NMDA receptors and only weak AMPA agonist effects.

  DOI：

  10.1021/jm00046a009
• 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， 以 乙醚 为溶剂， 反应 8.67h， 生成 3-甲氧基-4-甲基-5-(2-甲基-2-丙基)-1,2-恶唑
  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

• HERBICIDE TRIAZOLYLPYRIDINE KETONES
  申请人：Bayer CropScience AG

  公开号：US20130296168A1

  公开（公告）日：2013-11-07

  Triazolylpyridine ketones expressed by the following formula (1) and use thereof as herbicides.

  以下是Triazolylpyridine酮的化学式（1），以及其作为除草剂的应用。
• US8927458B2
  申请人：——

  公开号：US8927458B2

  公开（公告）日：2015-01-06
• Ibotenic Acid Analogues. Synthesis, Molecular Flexibility, and in Vitro Activity of Agonists and Antagonists at Central Glutamic Acid Receptors
  作者：Jørn Lauridsen、Tage Honoré、Povl Krogsgaard-Larsen

  DOI：10.1021/jm50001a022

  日期：1985.5

  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.
• Synthesis and Structure-Activity Studies on Acidic Amino Acids and Related Diacids as NMDA Receptor Ligands
  作者：Tommy N. Johansen、Karla Frydenvang、Bjarke Ebert、Povl Krogsgaard-Larsen、Ulf Madsen

  DOI：10.1021/jm00046a009

  日期：1994.9

  The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively, of(S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [H-3]CPP-binding assay (IC50 = 7 +/- 3 mu M) and electropharmacologically in the rat cortical wedge model (EC(50) = 8 +/- 2 mu M) In contrast to this, the tert-butyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a c were studied by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very weak basic character, 6 is a, perhaps subtype-selective, NMDA receptor agonist and a potent neurotoxic agent. These aspects prompted us to synthesize and test the diacids 8a,b, in which the amino group of AMAA, has been replaced by a methylthio and methoxy group, respectively. Neither compound showed significant affinity for nor depolarizing effects at NMDA receptors. The hydroxymethyl AMPA analogue 3c showed no interaction with NMDA receptors and only weak AMPA agonist effects.