ethyl 3-<(4-formylphenoxy)ethoxy>-4-<<2-(1-imidazolyl)ethyl>oxy>benzoate | 163163-75-5

• 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: ethyl 3-<(4-formylphenoxy)ethoxy>-4-<<2-(1-imidazolyl)ethyl>oxy>benzoate
• 英文别名: Ethyl 3-[2-(4-formylphenoxy)ethoxy]-4-(2-imidazol-1-ylethoxy)benzoate
• CAS: 163163-75-5
• 化学式: C₂₃H₂₄N₂O₆
• 分子量: 424.453
• InChiKey: LTMZHMWZIHKRHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  88.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-<(4-formylphenoxy)ethoxy>-4-<<2-(1-imidazolyl)ethyl>oxy>benzoate 在 sodium hydroxide 、 四丁基氟化铵 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 3-(2-{4-[(2R,4R,5S)-5-((Z)-5-Carboxy-pent-2-enyl)-4-(2-hydroxy-phenyl)-[1,3]dioxan-2-yl]-phenoxy}-ethoxy)-4-(2-imidazol-1-yl-ethoxy)-benzoic acid
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005
• 作为产物：
  描述：

  对羟基苯甲醛 在 sodium hydride 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 ethyl 3-<(4-formylphenoxy)ethoxy>-4-<<2-(1-imidazolyl)ethyl>oxy>benzoate
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005