D,L-2,6-dimethyl-3-(2,2,2-trifluoroethoxycarbonyl)-4-(3,5-difluorophenyl)-5-methoxycarbonyl-1,4-dihydropyridine

• 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: D,L-2,6-dimethyl-3-(2,2,2-trifluoroethoxycarbonyl)-4-(3,5-difluorophenyl)-5-methoxycarbonyl-1,4-dihydropyridine
• 英文别名: 3-O-methyl 5-O-(2,2,2-trifluoroethyl) 4-(3,5-difluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₁₈H₁₆F₅NO₄
• 分子量: 405.321
• InChiKey: BKFVCMGELXNVCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,2,2-trifluoroethyl 3-oxobutanoate 、 3,5-二氟苯甲醛 、 methyl (E)-3-aminocrotonate 以 异丙醇 为溶剂， 反应 20.0h， 以46%的产率得到D,L-2,6-dimethyl-3-(2,2,2-trifluoroethoxycarbonyl)-4-(3,5-difluorophenyl)-5-methoxycarbonyl-1,4-dihydropyridine
  参考文献：
  名称：

  Novel halogenated 1,4-dihydropyridines: Synthesis, bioassay, microsomal oxidation and structure-activity relationships

  摘要：

  Nine new 1,4-dihydropyridines (DHPs) were synthesized and evaluated for their relaxant ability (rat aorta) and their antihypertensive activity in spontaneously hypertensive rats; their microsomal oxidation rate (MOR) was determined. In terms of relaxant activity, the 4-(3,5-difluorophenyl) analogues were more potent than those with 4-(4-fluorophenyl) but weaker than those with 4-(3-nitrophenyl) substituents, while in terms of antihypertensive activity the 4-(3,5-difluorophenyl) derivatives were more potent than their 4-(3-nitrophenyl) analogues. Their MOR could be explained on the basis of the electron-withdrawing effect of the substituents, and in some cases they permitted a rationalization of discrepancies noted between DHP antihypertensive and relaxant activities. A parabolic relationship was found between the size of the carboxylic ester substituents and their contributions calculated from a Free-Wilson/Fujita-Ban analysis of relaxant activity data.

  DOI：

  10.1016/0223-5234(96)88245-6

文献信息

• Novel halogenated 1,4-dihydropyridines: Synthesis, bioassay, microsomal oxidation and structure-activity relationships
  作者：Z Hernández-Gallegos、PA Lehmann F、E Hong、F Posadas、E Hernández-Gallegos

  DOI：10.1016/0223-5234(96)88245-6

  日期：1995.1

  Nine new 1,4-dihydropyridines (DHPs) were synthesized and evaluated for their relaxant ability (rat aorta) and their antihypertensive activity in spontaneously hypertensive rats; their microsomal oxidation rate (MOR) was determined. In terms of relaxant activity, the 4-(3,5-difluorophenyl) analogues were more potent than those with 4-(4-fluorophenyl) but weaker than those with 4-(3-nitrophenyl) substituents, while in terms of antihypertensive activity the 4-(3,5-difluorophenyl) derivatives were more potent than their 4-(3-nitrophenyl) analogues. Their MOR could be explained on the basis of the electron-withdrawing effect of the substituents, and in some cases they permitted a rationalization of discrepancies noted between DHP antihypertensive and relaxant activities. A parabolic relationship was found between the size of the carboxylic ester substituents and their contributions calculated from a Free-Wilson/Fujita-Ban analysis of relaxant activity data.