1,2-Pyrrolidinedicarboxylic acid, 5-oxo-4-(5-thiazolylmethylene)-,bis(1,1-dimethylethyl) ester, (2S,4E)- | 660439-65-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,2-Pyrrolidinedicarboxylic acid, 5-oxo-4-(5-thiazolylmethylene)-,bis(1,1-dimethylethyl) ester, (2S,4E)-
• 英文别名: tert-butyl (S)-E-1-(tert-butoxycarbonyl)-4-[(thiazol-5-yl)methylene]pyroglutamate
• CAS: 660439-65-6
• 化学式: C₁₈H₂₄N₂O₅S
• 分子量: 380.465
• InChiKey: TZNSIJRDKUMIRI-HJTPGIPUSA-N

物化性质

• 沸点：
  481.0±55.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  85.8
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1,2-Pyrrolidinedicarboxylic acid, 5-oxo-4-(5-thiazolylmethylene)-,bis(1,1-dimethylethyl) ester, (2S,4E)- 在 lithium hydroxide 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (S)-E-4-[(thiazol-5-yl)methylene]glutamic acid dihydrobromide
  参考文献：
  名称：

  Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues

  摘要：

  2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid (1) is a potent AMPA receptor agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between I and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand and to indiscriminately bind to the AMPA receptor subtypes GluR1-4 with lower affinities. Compounds 4b-h, in which the 2-thiazolyl substituent of 4a was replaced by other heterocyclic rings, which have previously been incorporated as 5-substituents in AMPA analogues, as exemplified by 1 were also synthesized. Compounds 4b-h were either inactive (4e,f) or weaker than 4a as affinity ligands for GluR1-4 and GluR5 with relative potencies comparable with those of the corresponding AMPA analogues as AMPA receptor agonists. Compounds 4a-h may be useful tools for the progressing pharmacophore mapping of the GluR5 agonist binding site. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00485-1
• 作为产物：
  描述：

  2-(三甲基硅基)噻唑 、 tert-butyl (S)-1-(tert-butoxycarbonyl)-4-(dimethylaminomethylene)pyroglutamate 在 正丁基锂 、 magnesium bromide 作用下， 以 乙醚 、 正己烷 、 四氢呋喃 为溶剂， 反应 1.25h， 以62%的产率得到1,2-Pyrrolidinedicarboxylic acid, 5-oxo-4-(5-thiazolylmethylene)-,bis(1,1-dimethylethyl) ester, (2S,4E)-
  参考文献：
  名称：

  Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues

  摘要：

  2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid (1) is a potent AMPA receptor agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between I and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand and to indiscriminately bind to the AMPA receptor subtypes GluR1-4 with lower affinities. Compounds 4b-h, in which the 2-thiazolyl substituent of 4a was replaced by other heterocyclic rings, which have previously been incorporated as 5-substituents in AMPA analogues, as exemplified by 1 were also synthesized. Compounds 4b-h were either inactive (4e,f) or weaker than 4a as affinity ligands for GluR1-4 and GluR5 with relative potencies comparable with those of the corresponding AMPA analogues as AMPA receptor agonists. Compounds 4a-h may be useful tools for the progressing pharmacophore mapping of the GluR5 agonist binding site. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00485-1