6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid methyl ester | 1493777-21-1

• 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-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid methyl ester
• CAS: 1493777-21-1
• 化学式: C₁₆H₁₅ClN₂O₃
• 分子量: 318.76
• InChiKey: VBRMIRWYSXXRPR-UHFFFAOYSA-N

物化性质

• 沸点：
  435.9±45.0 °C(predicted)
• 密度：
  1.304±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.37
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.31
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid methyl ester 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 以94%的产率得到6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708
• 作为产物：
  描述：

  4-氯苯硼酸 在 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三甲基溴硅烷 、 一氧化碳 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 1,2-二溴乙烷 、 mineral oil 为溶剂， 20.0~110.0 ℃ 、7.0 MPa 条件下， 反应 26.75h， 生成 6-(4-chlorophenyl)-5-(cyclopropylmethoxy)-2-pyrazinecarboxylic acid methyl ester
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708