3,3-bis-(4-ethylphenyl)oxirane-2-carboxylic acid methyl ester

• 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-ethylphenyl)oxirane-2-carboxylic acid methyl ester
• 英文别名: Methyl 3,3-di(4-ethylphenyl)-2,3-epoxypropionate；methyl 3,3-bis(4-ethylphenyl)oxirane-2-carboxylate
• 化学式: C₂₀H₂₂O₃
• 分子量: 310.393
• InChiKey: CDMKBEVBWNBHNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,3-bis-(4-ethylphenyl)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 2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethoxy)-3,3-di(4-ethylphenyl)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：

  氯乙酸甲酯 、 双(4-乙基苯基)甲酮 、 sodium ethanolate 、 水 在 乙醚 、 碳酸氢钠 、 柠檬酸 、 magnesium sulfate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以15.4 g of a crude oil were isolated的产率得到3,3-bis-(4-ethylphenyl)oxirane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Azinyloxy, and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed ETA/ETB endothelin receptor antagonists

  摘要：

  本发明涉及式I的羧酸衍生物，其中基团具有描述中所述的含义，并且涉及它们作为药物的使用。

  公开号：

  US06670367B1

文献信息

• US6670367B1
  申请人：——

  公开号：US6670367B1

  公开（公告）日：2003-12-30
• Discovery and Synthesis of (<i>S</i>)-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
  作者：Willi Amberg、Stefan Hergenröder、Heinz Hillen、Rolf Jansen、Georg Kettschau、Andreas Kling、Dagmar Klinge、Manfred Raschack、Hartmut Riechers、Liliane Unger

  DOI：10.1021/jm9910425

  日期：1999.8.1

  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.
• Azinyloxy, and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed ETA/ETB endothelin receptor antagonists
  申请人：Abbott GmbH & Co., KG

  公开号：US06670367B1

  公开（公告）日：2003-12-30

  The invention relates to carboxylic acid derivatives of the formula I where the radicals have the meanings stated in the description, and to their use as drugs.

  本发明涉及式I的羧酸衍生物，其中基团具有描述中所述的含义，并且涉及它们作为药物的使用。