1-(tetrahydrofuran-2-yl)-5-trifluoromethylpyrimidine-2,4-dione | 25509-03-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(tetrahydrofuran-2-yl)-5-trifluoromethylpyrimidine-2,4-dione
• 英文别名: 1-tetrahydrofuran-2-yl-5-trifluoromethyl-1H-pyrimidine-2,4-dione；(2-tetrahydrofuryl)-5-trifluoromethyluracil；N-(2'-Furanidyl)-5-trifluormethyluracil；1-(Oxolan-2-yl)-5-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione；1-(oxolan-2-yl)-5-(trifluoromethyl)pyrimidine-2,4-dione
• CAS: 25509-03-9
• 化学式: C₉H₉F₃N₂O₃
• 分子量: 250.177
• InChiKey: RRIWAAONMPNFPS-UHFFFAOYSA-N

物化性质

• 熔点：
  193-194 °C (decomp)
• 密度：
  1.522±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(tetrahydrofuran-2-yl)-5-trifluoromethylpyrimidine-2,4-dione 在 sodium hydride 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-ylmethyl)-5-trifluoromethylpyrimidine-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：

  5-三氟甲基尿嘧啶 在 硫酸氢铵 、 六甲基二硅氮烷 作用下， 以 乙腈 为溶剂， 生成 1-(tetrahydrofuran-2-yl)-5-trifluoromethylpyrimidine-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

• Method for the preparation of derivatives of uracil
  申请人：Toshin Chemical Co., Ltd.

  公开号：US04159378A1

  公开（公告）日：1979-06-26

  A novel and very elegant method is proposed for the preparation of N.sub.1 -(2-tetrahydrofuryl)-5-substituted or -unsubstituted uracil, especially, N.sub.1 -(2-tetrahydrofuryl)-5-fluorouracil, by the reaction of the corresponding 5-substituted uracil compound with 2,3-dihydrofuran. The reaction is performed in the presence of a chlorosilane compound, e.g. dimethyldichlorosilane, and a catalytic amount of an organic amine compound and can proceed very rapidly without disadvantageous side reactions to give the objective compound with high purity in a high yield.

  提出了一种新颖而非常优雅的方法，用于制备N.sub.1-(2-四氢呋喃基)-5-取代或未取代尿嘧啶，特别是N.sub.1-(2-四氢呋喃基)-5-氟尿嘧啶，通过相应的5-取代尿嘧啶化合物与2,3-二氢呋喃的反应。在氯硅烷化合物（例如二甲基二氯硅烷）和有机胺化合物的催化下进行反应，可以非常迅速地进行，没有不利的副反应，从而以高纯度和高产率得到目标化合物。
• 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).