6-cyclopropyl-2-phenylpyrimidin-4-ol

• 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: 6-cyclopropyl-2-phenylpyrimidin-4-ol
• 英文别名: 4-Hydroxy-2-phenyl-6-cyclopropylpyrimidine；4-cyclopropyl-2-phenyl-1H-pyrimidin-6-one
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: RLMTYNZGMXOHKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-cyclopropyl-2-phenylpyrimidin-4-ol 在 potassium carbonate 、 caesium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 4-cyclopropyl-2-phenyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Sigma-1 Receptor Antagonists Based on Pyrimidine Scaffold As Agents for Treating Neuropathic Pain

  摘要：

  The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (sigma R-1) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor binding assays. The nature of the pyrimidine scaffold was crucial for activity, and a basic amine was shown to be necessary according to the known pharmacophoric model. The most promising derivative was 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine (137), which exhibited a high binding affinity to sigma R-1 receptor (K-i sigma(1) = 1.06 nM) and good sigma-1/2 selectivity (1344-fold). In in vivo tests, compound 137 exerted dose-dependent antinociceptive effects in mice formalin model and rats CCI models of neuropathic pain. In addition, no motor impairments were found in rotarod tests; acceptable pharmacokinetic properties were also noted. These data suggest compound 137 may constitute a novel class of drugs for the treatment of neuropathic pain.

  DOI：

  10.1021/jm501207r
• 作为产物：
  描述：

  苄脒盐酸盐 、 3-环丙基-3-羰基-丙酸乙酯 在 potassium carbonate 作用下， 以 水 为溶剂， 反应 0.25h， 以78%的产率得到6-cyclopropyl-2-phenylpyrimidin-4-ol
  参考文献：
  名称：

  超声促进的4-嘧啶醇及其甲苯磺酰基衍生物的合成

  摘要：

  摘要 超声波辐照以良好至优异的产率促进了β-酮酯和am的环缩合反应，形成了十六个高度取代的4-嘧啶醇。这些化合物的甲苯磺酸化，在另一个超声促进的转化中，以高收率形成了4-嘧啶甲苯磺酸盐。所制备的甲苯磺酸盐与苯基硼酸的Suzuki-Miyaura交叉偶联的三个例子说明了使用已开发的方案作为替代4-芳基嘧啶的方法。 超声波辐照以良好至优异的产率促进了β-酮酯和am的环缩合反应，形成了十六个高度取代的4-嘧啶醇。这些化合物的甲苯磺酸化，在另一个超声促进的转化中，以高收率形成了4-嘧啶甲苯磺酸盐。所制备的甲苯磺酸盐与苯基硼酸的Suzuki-Miyaura交叉偶联的三个例子说明了使用已开发的方案作为替代4-芳基嘧啶的方法。

  DOI：

  10.1055/s-0035-1562788

文献信息

• Synthesis and Biological Evaluation of Novel Sigma-1 Receptor Antagonists Based on Pyrimidine Scaffold As Agents for Treating Neuropathic Pain
  作者：Yu Lan、Yin Chen、Xudong Cao、Juecheng Zhang、Jie Wang、Xiangqing Xu、Yinli Qiu、Tan Zhang、Xin Liu、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/jm501207r

  日期：2014.12.26

  The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (sigma R-1) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor binding assays. The nature of the pyrimidine scaffold was crucial for activity, and a basic amine was shown to be necessary according to the known pharmacophoric model. The most promising derivative was 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine (137), which exhibited a high binding affinity to sigma R-1 receptor (K-i sigma(1) = 1.06 nM) and good sigma-1/2 selectivity (1344-fold). In in vivo tests, compound 137 exerted dose-dependent antinociceptive effects in mice formalin model and rats CCI models of neuropathic pain. In addition, no motor impairments were found in rotarod tests; acceptable pharmacokinetic properties were also noted. These data suggest compound 137 may constitute a novel class of drugs for the treatment of neuropathic pain.
• Ultrasound-Promoted Synthesis of 4-Pyrimidinols and Their Tosyl Derivatives
  作者：Moisés Domínguez、Matías Vidal、Macarena García-Arriagada、Marcos Rezende

  DOI：10.1055/s-0035-1562788

  日期：——

  the prepared tosylates with phenylboronic acid. Ultrasound irradiation promoted the cyclocondensation of β-keto esters and amidines in good to excellent yields to form sixteen highly substituted 4-pyrimidinols. Tosylation of these compounds, in another ultrasound-promoted conversion, formed 4-pyrimidyl tosylates in high yields. The use of the developed protocol as an alternative route to 4-arylpyrimidines

  摘要 超声波辐照以良好至优异的产率促进了β-酮酯和am的环缩合反应，形成了十六个高度取代的4-嘧啶醇。这些化合物的甲苯磺酸化，在另一个超声促进的转化中，以高收率形成了4-嘧啶甲苯磺酸盐。所制备的甲苯磺酸盐与苯基硼酸的Suzuki-Miyaura交叉偶联的三个例子说明了使用已开发的方案作为替代4-芳基嘧啶的方法。 超声波辐照以良好至优异的产率促进了β-酮酯和am的环缩合反应，形成了十六个高度取代的4-嘧啶醇。这些化合物的甲苯磺酸化，在另一个超声促进的转化中，以高收率形成了4-嘧啶甲苯磺酸盐。所制备的甲苯磺酸盐与苯基硼酸的Suzuki-Miyaura交叉偶联的三个例子说明了使用已开发的方案作为替代4-芳基嘧啶的方法。