2-Acetyl-3-phenyl-4-(5-phenyl-isoxazol-3-yl)-pentanedioic acid diethyl ester | 114957-77-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 2-Acetyl-3-phenyl-4-(5-phenyl-isoxazol-3-yl)-pentanedioic acid diethyl ester
• CAS: 114957-77-6
• 化学式: C₂₆H₂₇NO₆
• 分子量: 449.503
• InChiKey: ZHMYBVZNORPYTD-UHFFFAOYSA-N

物化性质

• 沸点：
  600.1±55.0 °C(predicted)
• 密度：
  1.186±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  33.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  95.7
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-Acetyl-3-phenyl-4-(5-phenyl-isoxazol-3-yl)-pentanedioic acid diethyl ester 在 molybdenum hexacarbonyl 作用下， 以 水 、 乙腈 为溶剂， 反应 23.0h， 以16%的产率得到(3S,4R)-6-Methyl-2-[2-oxo-2-phenyl-eth-(Z)-ylidene]-4-phenyl-1,2,3,4-tetrahydro-pyridine-3,5-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers

  摘要：

  The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

  DOI：

  10.1021/jm00403a030
• 作为产物：
  描述：

  ethyl 5-phenyl-3,5-dioxopentanoate 在 盐酸羟胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 1.33h， 生成 2-Acetyl-3-phenyl-4-(5-phenyl-isoxazol-3-yl)-pentanedioic acid diethyl ester
  参考文献：
  名称：

  2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers

  摘要：

  The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

  DOI：

  10.1021/jm00403a030