1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione | 205653-99-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione
• 英文别名: 1-[4-(2-Hydroxyethoxy)-3-methoxy-5-nitrophenyl]-4-(3,4,5-trimethoxyphenyl)butane-1,4-dione
• CAS: 205653-99-2
• 化学式: C₂₂H₂₅NO₁₀
• 分子量: 463.441
• InChiKey: PAAMBPGZDLVNAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  146
• 氢给体数：
  1
• 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-butanedione 在 sodium tetrahydroborate 、 三乙胺 、 三氟乙酸 、 calcium chloride 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 42.0h， 生成 (+/-)-trans-2-[3-methoxy-4-(4-methoxyphenylthioethoxy)-5-(N-butyl-N-hydroxyureidyl)phenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran
  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：

  2-丙烯-1-酮,1-(3,4,5-三甲氧苯基)- 、 3-methoxy-4-hydroxyethoxy-5-nitrobenzaldehyde 在 3-苄基羟乙基甲基噻唑氯化锂 、 三乙胺 作用下， 反应 16.0h， 以60%的产率得到1-(3-methoxy-4-hydroxyethoxy-5-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione
  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

文献信息

• (±)-<i>trans</i>-2-[3-Methoxy-4-(4-chlorophenylthioethoxy)-5-(<i>N</i>-methyl-<i>N</i>- hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a Potent Dual 5-Lipoxygenase Inhibitor and Platelet-Activating Factor Receptor Antagonist
  作者：Xiong Cai、Ralph T. Scannell、David Yaeger、Md. Sajjat Hussoin、David B. Killian、Changgeng Qian、Joseph Eckman、San-Bao Hwang、Lynn Libertine-Garahan、C. Grace Yeh、Stephen H. Ip、T. Y. Shen

  DOI：10.1021/jm980046r

  日期：1998.5.1

  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.