2-Hydroxy-3,3-diphenyl-3-[(E)-3-(3,4,5-trimethoxy-phenyl)-allyloxy]-propionic acid methyl ester | 1026321-57-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-Hydroxy-3,3-diphenyl-3-[(E)-3-(3,4,5-trimethoxy-phenyl)-allyloxy]-propionic acid methyl ester
• 英文别名: methyl 2-hydroxy-3,3-diphenyl-3-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoxy]propanoate
• CAS: 1026321-57-2
• 化学式: C₂₈H₃₀O₇
• 分子量: 478.542
• InChiKey: FIMWPWRGEMNFRN-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-Hydroxy-3,3-diphenyl-3-[(E)-3-(3,4,5-trimethoxy-phenyl)-allyloxy]-propionic acid methyl ester 在 sodium hydroxide 、 lithium amide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 3-<3-(3,4,5-trimethoxyphenyl)prop-(2E)-enoxy>-2-<(4,6-dimethylpyrimidin-2-yl)oxy>-3,3-diphenylpropionic acid
  参考文献：
  名称：

  Discovery and Synthesis of (S)-3-[2-(3,4-Dimethoxyphenyl)ethoxy]-2- (4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic Acid (LU 302872), a Novel Orally Active Mixed ET_A/ET_B Receptor Antagonist

  摘要：

  Structural variation of the endothelin A-selective antagonist (S)-3-methoxy-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 135252) led to analogues which retain ETA affinity but exhibit substantial ETB affinity as well. The most active derivative obtained is (S)-3- [2-(3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K-i = 2.15 nM far binding to the ETA receptor and a K-i = 4.75 nM for binding to the ETB receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.

  DOI：

  10.1021/jm9910425
• 作为产物：
  描述：

  反式-3,4,5-三甲氧基肉桂醇 、 3, 3-二苯基-2,3-环氧丙酸甲酯 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-Hydroxy-3,3-diphenyl-3-[(E)-3-(3,4,5-trimethoxy-phenyl)-allyloxy]-propionic acid methyl ester
  参考文献：
  名称：

  Discovery and Synthesis of (S)-3-[2-(3,4-Dimethoxyphenyl)ethoxy]-2- (4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic Acid (LU 302872), a Novel Orally Active Mixed ET_A/ET_B Receptor Antagonist

  摘要：

  Structural variation of the endothelin A-selective antagonist (S)-3-methoxy-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 135252) led to analogues which retain ETA affinity but exhibit substantial ETB affinity as well. The most active derivative obtained is (S)-3- [2-(3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K-i = 2.15 nM far binding to the ETA receptor and a K-i = 4.75 nM for binding to the ETB receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.

  DOI：

  10.1021/jm9910425