4-(2-chloro-4-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester | 112969-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(2-chloro-4-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 4-(2-chloro-4-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 112969-07-0
• 化学式: C₁₇H₁₇ClN₂O₆
• 分子量: 380.785
• InChiKey: BFTOERDJDKTEKN-UHFFFAOYSA-N

物化性质

• 沸点：
  494.2±45.0 °C(Predicted)
• 密度：
  1.339±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氯-4-硝基苯甲醛 、 乙酰乙酸甲酯 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以25%的产率得到4-(2-chloro-4-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Studies directed toward ascertaining the active conformation of 1,4-dihydropyridine calcium entry blockers

  摘要：

  A series of unsymmetrically substituted 4-phenyl-1,4-dihydropyridine calcium entry blockers were investigated for their ability to relax potassium-contracted rabbit aortic smooth muscle and to competitively displace [3H]nitrendipine from its specific binding sites on guinea pig myocardial membranes in order to delineate the pharmacologically active conformer with respect to the position of the aromatic substituent (synperiplanar or antiperiplanar). The data show that the 1,4-dihydropyridine receptor distinguishes between 2',3'-disubstituted phenyldihydropyridines and 2',5'-disubstituted analogues as measured by changes of vasodilation and receptor affinity in vitro. The IC50 values for vasorelaxation by the analogues presented here correlate best with the Kd values for binding to the predominant receptor of two coexisting dihydropyridine binding sites in the guinea pig myocardium. We report the first observation of an antiperiplanar orientation of an o-phenyl substituent in the X-ray structure of 2-chlorophenyl analogue 3. Using nuclear Overhauser enhancement, we have developed a method that also demonstrates that an ortho (chloro or nitro) substituent on the phenyl ring does not preclude the presence of either synperiplanar or antiperiplanar phenyl rotamer in solution. These experimental findings contrast with the accepted belief that o-phenyl substituents essentially force these 1,4-dihydropyridines into the synperiplanar conformation exclusively.

  DOI：

  10.1021/jm00400a008

文献信息

• Studies directed toward ascertaining the active conformation of 1,4-dihydropyridine calcium entry blockers
  作者：George Rovnyak、Niels Andersen、Jack Gougoutas、Anders Hedberg、S. David Kimball、Mary Malley、Suzanne Moreland、Michael Porubcan、Andrew Pudzianowski

  DOI：10.1021/jm00400a008

  日期：1988.5

  A series of unsymmetrically substituted 4-phenyl-1,4-dihydropyridine calcium entry blockers were investigated for their ability to relax potassium-contracted rabbit aortic smooth muscle and to competitively displace [3H]nitrendipine from its specific binding sites on guinea pig myocardial membranes in order to delineate the pharmacologically active conformer with respect to the position of the aromatic substituent (synperiplanar or antiperiplanar). The data show that the 1,4-dihydropyridine receptor distinguishes between 2',3'-disubstituted phenyldihydropyridines and 2',5'-disubstituted analogues as measured by changes of vasodilation and receptor affinity in vitro. The IC50 values for vasorelaxation by the analogues presented here correlate best with the Kd values for binding to the predominant receptor of two coexisting dihydropyridine binding sites in the guinea pig myocardium. We report the first observation of an antiperiplanar orientation of an o-phenyl substituent in the X-ray structure of 2-chlorophenyl analogue 3. Using nuclear Overhauser enhancement, we have developed a method that also demonstrates that an ortho (chloro or nitro) substituent on the phenyl ring does not preclude the presence of either synperiplanar or antiperiplanar phenyl rotamer in solution. These experimental findings contrast with the accepted belief that o-phenyl substituents essentially force these 1,4-dihydropyridines into the synperiplanar conformation exclusively.