diethyl 3-[(3-(4-(methoxycarbonyl)thiophen-3-yl)ureido)methyl]thiophen-2-phosphonate | 1312367-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: diethyl 3-[(3-(4-(methoxycarbonyl)thiophen-3-yl)ureido)methyl]thiophen-2-phosphonate
• 英文别名: Methyl 4-[(2-diethoxyphosphorylthiophen-3-yl)methylcarbamoylamino]thiophene-3-carboxylate
• CAS: 1312367-22-8
• 化学式: C₁₆H₂₁N₂O₆PS₂
• 分子量: 432.458
• InChiKey: ONOJJRANFUXSIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl 3-[(3-(4-(methoxycarbonyl)thiophen-3-yl)ureido)methyl]thiophen-2-phosphonate 在 sodium ethanolate 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (S)-1-[2'-(tert-butoxycarbonylamino)-2'-carboxyethyl]-3-[(2-diethylphosphonothien-3-yl)methyl]thieno[3,4-d]pyrimidin-2,4-dione
  参考文献：
  名称：

  Selective Kainate Receptor (GluK1) Ligands Structurally Based upon 1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: Synthesis, Molecular Modeling, and Pharmacological and Biostructural Characterization

  摘要：

  The physiological function of kainate receptors (GluK1-GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacological evaluation revealed that they are selective for the GluK1 subunit, with 7b being the most subtype-selective ligand reported to date (GluK1 vs GluK3). The antagonist 7a was cocrystallized with the GluK1 ligand binding domain, and an X-ray crystallographic analysis revealed the largest flexibility in GluK1 ligand binding domain opening upon binding of a ligand seen to date. The results provide new insights into the molecular Mechanism of GluK1 receptor ligand binding and pave the way to the development of new tool compounds for studying kainate receptor function.

  DOI：

  10.1021/jm2004078
• 作为产物：
  描述：

  2-溴-3-甲基噻吩 在 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 偶氮二异丁腈 、 palladium on activated charcoal 、 氢气 、 nickel dichloride 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 diethyl 3-[(3-(4-(methoxycarbonyl)thiophen-3-yl)ureido)methyl]thiophen-2-phosphonate
  参考文献：
  名称：

  Selective Kainate Receptor (GluK1) Ligands Structurally Based upon 1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: Synthesis, Molecular Modeling, and Pharmacological and Biostructural Characterization

  摘要：

  The physiological function of kainate receptors (GluK1-GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacological evaluation revealed that they are selective for the GluK1 subunit, with 7b being the most subtype-selective ligand reported to date (GluK1 vs GluK3). The antagonist 7a was cocrystallized with the GluK1 ligand binding domain, and an X-ray crystallographic analysis revealed the largest flexibility in GluK1 ligand binding domain opening upon binding of a ligand seen to date. The results provide new insights into the molecular Mechanism of GluK1 receptor ligand binding and pave the way to the development of new tool compounds for studying kainate receptor function.

  DOI：

  10.1021/jm2004078