2,6-Dimethyl-4-naphthalen-1-yl-pyridine-3,5-dicarboxylic acid dimethyl ester | 133349-26-5

• 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: 2,6-Dimethyl-4-naphthalen-1-yl-pyridine-3,5-dicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 2,6-dimethyl-4-naphthalen-1-ylpyridine-3,5-dicarboxylate
• CAS: 133349-26-5
• 化学式: C₂₁H₁₉NO₄
• 分子量: 349.386
• InChiKey: ZJVLBAVQDJUKKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  dimethyl 1,4-dihydro-2,6-dimethyl-4-(1-naphthyl)-3,5-dicarboxylate 在 potassium phosphate 、 乙二胺四乙酸 、 Emulgen 911 、 human liver cytochrome b₅ 、 human liver HL 39 lipid extract 、 rabbit liver NADPH-P-450 reductase 、 yeast P-450 IIIA₄ 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 2,6-Dimethyl-4-naphthalen-1-yl-pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4

  摘要：

  A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was approximately 10(3) times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-4.50 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.

  DOI：

  10.1021/jm00110a012