1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol | 205654-00-8

• 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: 1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol
• 英文别名: 1-[4-(2-Hydroxyethoxy)-3-methoxy-5-nitrophenyl]-4-(3,4,5-trimethoxyphenyl)butane-1,4-diol
• CAS: 205654-00-8
• 化学式: C₂₂H₂₉NO₁₀
• 分子量: 467.473
• InChiKey: KLVLJABWJJUJEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol 在 三乙胺 、 三氟乙酸 、 calcium chloride 、 锌 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 37.0h， 生成 2-[2-(4-Bromo-phenylsulfanyl)-ethoxy]-3-methoxy-5-[(2S,5S)-5-(3,4,5-trimethoxy-phenyl)-tetrahydro-furan-2-yl]-phenylamine
  参考文献：
  名称：

  (±)-trans-2-[3-Methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N- hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a Potent Dual 5-Lipoxygenase Inhibitor and Platelet-Activating Factor Receptor Antagonist

  摘要：

  By incorporating an N-hydroxyurea functionality onto diaryltetrahydrofurans, a novel series of compounds was investigated as dual 5-lipoxygenese (5-LO) inhibitor and platelet-activating factor (PAF) receptor antagonist. These dual functional compounds were evaluated in vitro for 5-LO inhibition in RBL cell extracts and human whole blood, and PAF receptor antagonism in a receptor binding assay. PAF-induced hemoconcentration and arachidonic acid-and TPA-induced ear edema in mice were used to determine in vivo activities. The structure-activity relationship analysis to define a preclinical lead is presented. (+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (40, CMI-392) was selected for further study. In the arachidonic acid-induced mouse ear edema model, 40 was more potent than either zileuton (a 5-LO inhibitor) or BN 50739 (a PAF receptor antagonist), and it demonstrated the same inhibitory effect as a physical combination of the latter two agents. These results suggest that a single compound which both inhibits leukotriene synthesis and blocks PAF receptor binding may provide therapeutic advantages over single-acting agents. The clinical development of compound 40 is in progress.

  DOI：

  10.1021/jm980046r
• 作为产物：
  描述：

  3-methoxy-4-hydroxyethoxy-5-nitrobenzaldehyde 在 sodium tetrahydroborate 、 3-苄基羟乙基甲基噻唑氯化锂 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 19.0h， 生成 1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol
  参考文献：
  名称：

  (±)-trans-2-[3-Methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N- hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a Potent Dual 5-Lipoxygenase Inhibitor and Platelet-Activating Factor Receptor Antagonist

  摘要：

  By incorporating an N-hydroxyurea functionality onto diaryltetrahydrofurans, a novel series of compounds was investigated as dual 5-lipoxygenese (5-LO) inhibitor and platelet-activating factor (PAF) receptor antagonist. These dual functional compounds were evaluated in vitro for 5-LO inhibition in RBL cell extracts and human whole blood, and PAF receptor antagonism in a receptor binding assay. PAF-induced hemoconcentration and arachidonic acid-and TPA-induced ear edema in mice were used to determine in vivo activities. The structure-activity relationship analysis to define a preclinical lead is presented. (+/-)-trans-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (40, CMI-392) was selected for further study. In the arachidonic acid-induced mouse ear edema model, 40 was more potent than either zileuton (a 5-LO inhibitor) or BN 50739 (a PAF receptor antagonist), and it demonstrated the same inhibitory effect as a physical combination of the latter two agents. These results suggest that a single compound which both inhibits leukotriene synthesis and blocks PAF receptor binding may provide therapeutic advantages over single-acting agents. The clinical development of compound 40 is in progress.

  DOI：

  10.1021/jm980046r