3-(2-methoxycarbonylbenzyl)-5-methyl-1-(tetrahydrofuran-2-yl)pyrimidine-2,4-dione | 936095-23-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2-methoxycarbonylbenzyl)-5-methyl-1-(tetrahydrofuran-2-yl)pyrimidine-2,4-dione
• 英文别名: Methyl 2-[[5-methyl-2,6-dioxo-3-(oxolan-2-yl)pyrimidin-1-yl]methyl]benzoate
• CAS: 936095-23-7
• 化学式: C₁₈H₂₀N₂O₅
• 分子量: 344.367
• InChiKey: YBRRMEUBYUIZPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-methoxycarbonylbenzyl)-5-methyl-1-(tetrahydrofuran-2-yl)pyrimidine-2,4-dione 在 lithium hydroxide 、 sodium hydride 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl)-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of N³-Substituted Willardiine Derivatives:  Role of the Substituent at the 5-Position of the Uracil Ring in the Development of Highly Potent and Selective GLU_K5 Kainate Receptor Antagonists

  摘要：

  Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2).

  DOI：

  10.1021/jm061041u
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.0h， 生成 3-(2-methoxycarbonylbenzyl)-5-methyl-1-(tetrahydrofuran-2-yl)pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of N³-Substituted Willardiine Derivatives:  Role of the Substituent at the 5-Position of the Uracil Ring in the Development of Highly Potent and Selective GLU_K5 Kainate Receptor Antagonists

  摘要：

  Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2).

  DOI：

  10.1021/jm061041u

文献信息

• Synthesis and Pharmacological Characterization of N³-Substituted Willardiine Derivatives:  Role of the Substituent at the 5-Position of the Uracil Ring in the Development of Highly Potent and Selective GLU_K5 Kainate Receptor Antagonists
  作者：Nigel P. Dolman、Julia C. A. More、Andrew Alt、Jody L. Knauss、Olli T. Pentikäinen、Carla R. Glasser、David Bleakman、Mark L. Mayer、Graham L. Collingridge、David E. Jane

  DOI：10.1021/jm061041u

  日期：2007.4.1

  Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2).