3,3-Bis-(4-chloro-phenyl)-3-[2-(3,4-dimethoxy-phenyl)-ethoxy]-2-hydroxy-propionic acid | 1027901-32-1

• 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: 3,3-Bis-(4-chloro-phenyl)-3-[2-(3,4-dimethoxy-phenyl)-ethoxy]-2-hydroxy-propionic acid
• 英文别名: 3,3-Bis(4-chlorophenyl)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2-hydroxypropanoic acid
• CAS: 1027901-32-1
• 化学式: C₂₅H₂₄Cl₂O₆
• 分子量: 491.368
• InChiKey: KQYQTONIBYUBSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-甲基-4-甲氧基-2-甲磺酰基嘧啶 、 3,3-Bis-(4-chloro-phenyl)-3-[2-(3,4-dimethoxy-phenyl)-ethoxy]-2-hydroxy-propionic acid 在 lithium amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-<2-(3,4-dimethoxyphenyl)ethoxy>-2-<(4-methoxy-6-methylpyrimidin-2-yl)oxy>-3,3-bis-(4-chlorophenyl)propionic 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：

  3,3-bis-(4-chlorophenyl)oxirane-2-carboxylic acid methyl ester 在 sodium hydroxide 、 三氟化硼乙醚 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3,3-Bis-(4-chloro-phenyl)-3-[2-(3,4-dimethoxy-phenyl)-ethoxy]-2-hydroxy-propionic 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