2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-nitrophenyl)-1,4-dihydropyridine | 256219-09-7

• 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: 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-nitrophenyl)-1,4-dihydropyridine
• 英文别名: Dimethyl 4-[2-(difluoromethoxy)-5-nitrophenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate；dimethyl 4-[2-(difluoromethoxy)-5-nitrophenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 256219-09-7
• 化学式: C₁₈H₁₈F₂N₂O₇
• 分子量: 412.347
• InChiKey: CKXVFIPITDNXJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-nitrophenyl)-1,4-dihydropyridine 在 氢气 、 镍 、 三乙胺 、 三苯基膦 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Vasorelaxation by New Hybrid Compounds Containing Dihydropyridine and Pinacidil-Like Moieties

  摘要：

  The synthesis and pharmacological properties of a novel type of vasorelaxant hybrid compounds are described. The investigated compounds originate from fluorinated 4-aryl-1,4-dihydropyridines, which are known calcium channel blockers, and/or from fluorinated analogues of pinacidil, which is an opener of ATP-sensitive potassium channels. In particular, we studied the most potent hybrid, 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-N-(N "-cyano-N'-1,2,2-trimethyl-propylguanidyl)-phenyl)-1,4-dihydropyridine (4a), together with its parent compounds, the dihydropyridine 1b and the pinacidil analogue 3. In isolated rat mesenteric arteries, micromolar concentrations of 4a relaxed contractions exerted by K+-depolarization or by norepinephrine. The latter effect was sensitive to the potassium channel blocker glibenclamide. Micromolar 4a also inhibited [H-3](+)-isradipine and [H-3]P1075 binding to rat cardiac membranes, and it blocked L-type calcium. channels expressed in a mammalian cell line. The respective parent compounds 1b and 3 were always more potent and more selective regarding calcium channel or potassium channel interaction, respectively. In contrast, 4a combined both effects within the same concentration range, indicating that it may represent a lead structure for a novel class of pharmacological hybrid compounds.

  DOI：

  10.1021/jm990443h
• 作为产物：
  描述：

  (二氟甲氧基)苯甲醛 在 硫酸 、 硝酸 作用下， 以 甲醇 为溶剂， 反应 9.0h， 生成 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-nitrophenyl)-1,4-dihydropyridine
  参考文献：
  名称：

  Vasorelaxation by New Hybrid Compounds Containing Dihydropyridine and Pinacidil-Like Moieties

  摘要：

  The synthesis and pharmacological properties of a novel type of vasorelaxant hybrid compounds are described. The investigated compounds originate from fluorinated 4-aryl-1,4-dihydropyridines, which are known calcium channel blockers, and/or from fluorinated analogues of pinacidil, which is an opener of ATP-sensitive potassium channels. In particular, we studied the most potent hybrid, 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-N-(N "-cyano-N'-1,2,2-trimethyl-propylguanidyl)-phenyl)-1,4-dihydropyridine (4a), together with its parent compounds, the dihydropyridine 1b and the pinacidil analogue 3. In isolated rat mesenteric arteries, micromolar concentrations of 4a relaxed contractions exerted by K+-depolarization or by norepinephrine. The latter effect was sensitive to the potassium channel blocker glibenclamide. Micromolar 4a also inhibited [H-3](+)-isradipine and [H-3]P1075 binding to rat cardiac membranes, and it blocked L-type calcium. channels expressed in a mammalian cell line. The respective parent compounds 1b and 3 were always more potent and more selective regarding calcium channel or potassium channel interaction, respectively. In contrast, 4a combined both effects within the same concentration range, indicating that it may represent a lead structure for a novel class of pharmacological hybrid compounds.

  DOI：

  10.1021/jm990443h

文献信息

• Vasorelaxation by New Hybrid Compounds Containing Dihydropyridine and Pinacidil-Like Moieties
  作者：Lev M. Yagupolskii、Wolfram Antepohl、Ferruh Artunc、Renate Handrock、Boris M. Klebanov、Irina I. Maletina、Bent Marxen、Kirill I. Petko、Ulrich Quast、Anna Vogt、Carolin Weiss、Jutta Zibold、Stefan Herzig

  DOI：10.1021/jm990443h

  日期：1999.12.1

  The synthesis and pharmacological properties of a novel type of vasorelaxant hybrid compounds are described. The investigated compounds originate from fluorinated 4-aryl-1,4-dihydropyridines, which are known calcium channel blockers, and/or from fluorinated analogues of pinacidil, which is an opener of ATP-sensitive potassium channels. In particular, we studied the most potent hybrid, 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-N-(N "-cyano-N'-1,2,2-trimethyl-propylguanidyl)-phenyl)-1,4-dihydropyridine (4a), together with its parent compounds, the dihydropyridine 1b and the pinacidil analogue 3. In isolated rat mesenteric arteries, micromolar concentrations of 4a relaxed contractions exerted by K+-depolarization or by norepinephrine. The latter effect was sensitive to the potassium channel blocker glibenclamide. Micromolar 4a also inhibited [H-3](+)-isradipine and [H-3]P1075 binding to rat cardiac membranes, and it blocked L-type calcium. channels expressed in a mammalian cell line. The respective parent compounds 1b and 3 were always more potent and more selective regarding calcium channel or potassium channel interaction, respectively. In contrast, 4a combined both effects within the same concentration range, indicating that it may represent a lead structure for a novel class of pharmacological hybrid compounds.