1,4-dihydro-2,6-dimethyl-4-(2-chloro-6-fluorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester | 86408-11-9

• 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: 1,4-dihydro-2,6-dimethyl-4-(2-chloro-6-fluorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 4-(2-chloro-6-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 86408-11-9
• 化学式: C₁₇H₁₇ClFNO₄
• mdl: MFCD01462444
• 分子量: 353.778
• InChiKey: ITTXNNGVEHGVPB-UHFFFAOYSA-N

物化性质

• 沸点：
  419.0±45.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 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：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-2,6-dimethyl-4-(2-chloro-6-fluorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester 在 硝酸 作用下， 反应 1.0h， 以82%的产率得到4-(2-Chloro-6-fluoro-phenyl)-2,6-dimethyl-pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  人肝微粒体对4-芳基和4-烷基取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶的氧化作用和涉及细胞色素P-450形式的免疫化学证据。

  摘要：

  4-取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶很重要，因为它们作为钙通道阻滞剂。检查了人肝微粒体对14个4-芳基和四个4-烷基取代的衍生物的混合功能氧化。所有4-芳基化合物的酶促氧化的主要产物是含有4-芳基的吡啶衍生物。相反，4-烷基化合物形成吡啶衍生物，其中在4-位存在氢原子并且烷基丢失；这些化合物还使细胞色素P-450失活，并在酶促氧化后导致硝苯地平氧化酶活性丧失。所有这些反应均受到针对纯化的人肝硝苯地平氧化酶细胞色素P-450（P-450NF）的抗体的抑制，表明该酶在这些化合物的氧化中起主要作用。4-烷基化合物的氧化不仅导致P-450NF的损失，而且还导致细胞色素P-450同工酶催化其他反应（非那西丁O-去乙基化和己糖3'-羟基化）的催化活性降低。结果表明，P-450NF（或密切相关的酶形式）负责人肝微粒体中这些硝苯地平相关化合物的氧化，并且代谢高度依赖于4-取

  DOI：

  10.1021/jm00159a007
• 作为产物：
  描述：

  2-氯-6-氟-苯甲醛 、 乙酰乙酸甲酯 在 氨 作用下， 以 甲醇 为溶剂， 以36%的产率得到1,4-dihydro-2,6-dimethyl-4-(2-chloro-6-fluorophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester
  参考文献：
  名称：

  1,4-Dihydropyridine antagonist activities at the calcium channel: a quantitative structure-activity relationship approach

  摘要：

  The effect of 46 1,4-dihydropyridine-type calcium channel antagonists on the tonic contractile response of longitudinal muscle strips of guinea pig ileum was determined. 2,6-Dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine (13) and 13 ortho-, 15 meta-, and seven para-monosubstituted and 10 polysubstituted aromatic derivatives of 13 were studied. The pharmacological activities of the monosubstituted derivatives were best correlated by eq 10, log 1/C = 0.68 pi + 2.50 sigma m -0.47Lmeta -3.40B1para + 11.31, which had a correlation coefficient of 0.89. The full data set was best correlated by eq 11, log 1/C = 0.62 pi + 1.96 sigma m -0.44Lmeta -3.26B1para -1.51Lmeta' + 14.23, which had a correlation coefficient of 0.90. Equations of similar form but involving an ortho steric term were found to correlate the radioligand binding data for this class of compounds.

  DOI：

  10.1021/jm00119a009

文献信息

• Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450
  作者：Ronald H. Boecker、F. Peter Guengerich

  DOI：10.1021/jm00159a007

  日期：1986.9

  lost; these compounds also inactivated cytochrome P-450 and caused the loss of nifedipine oxidase activity after enzymatic oxidation. All of these reactions were extensively inhibited by an antibody raised to purified human liver nifedipine oxidase cytochrome P-450 (P-450NF), indicating a major role for this enzyme in the oxidation of these compounds. Oxidation of the 4-alkyl compounds led not only

  4-取代的2,6-二甲基-3,5-双（烷氧基羰基）-1,4-二氢吡啶很重要，因为它们作为钙通道阻滞剂。检查了人肝微粒体对14个4-芳基和四个4-烷基取代的衍生物的混合功能氧化。所有4-芳基化合物的酶促氧化的主要产物是含有4-芳基的吡啶衍生物。相反，4-烷基化合物形成吡啶衍生物，其中在4-位存在氢原子并且烷基丢失；这些化合物还使细胞色素P-450失活，并在酶促氧化后导致硝苯地平氧化酶活性丧失。所有这些反应均受到针对纯化的人肝硝苯地平氧化酶细胞色素P-450（P-450NF）的抗体的抑制，表明该酶在这些化合物的氧化中起主要作用。4-烷基化合物的氧化不仅导致P-450NF的损失，而且还导致细胞色素P-450同工酶催化其他反应（非那西丁O-去乙基化和己糖3'-羟基化）的催化活性降低。结果表明，P-450NF（或密切相关的酶形式）负责人肝微粒体中这些硝苯地平相关化合物的氧化，并且代谢高度依赖于4-取
• 1,4-Dihydropyridine antagonist activities at the calcium channel: a quantitative structure-activity relationship approach
  作者：Robert A. Coburn、Mark Wierzba、Mark J. Suto、Alan J. Solo、A. M. Triggle、David J. Triggle

  DOI：10.1021/jm00119a009

  日期：1988.11

  The effect of 46 1,4-dihydropyridine-type calcium channel antagonists on the tonic contractile response of longitudinal muscle strips of guinea pig ileum was determined. 2,6-Dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine (13) and 13 ortho-, 15 meta-, and seven para-monosubstituted and 10 polysubstituted aromatic derivatives of 13 were studied. The pharmacological activities of the monosubstituted derivatives were best correlated by eq 10, log 1/C = 0.68 pi + 2.50 sigma m -0.47Lmeta -3.40B1para + 11.31, which had a correlation coefficient of 0.89. The full data set was best correlated by eq 11, log 1/C = 0.62 pi + 1.96 sigma m -0.44Lmeta -3.26B1para -1.51Lmeta' + 14.23, which had a correlation coefficient of 0.90. Equations of similar form but involving an ortho steric term were found to correlate the radioligand binding data for this class of compounds.