methyl (Z,7R,8S)-8-hydroxy-7-(hydroxymethyl)-8-pyridin-3-yloct-4-enoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (Z,7R,8S)-8-hydroxy-7-(hydroxymethyl)-8-pyridin-3-yloct-4-enoate
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: JXHRHQQKLUPGLI-KXAWDHGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-2-(2-nitro-4-methylphenoxy)propanal 、 methyl (Z,7R,8S)-8-hydroxy-7-(hydroxymethyl)-8-pyridin-3-yloct-4-enoate 在 对甲苯磺酸 、 原甲酸三甲酯 作用下， 以 乙腈 为溶剂， 以78%的产率得到(Z)-6-{(2S,4S,5R)-2-[1-Methyl-1-(4-methyl-2-nitro-phenoxy)-ethyl]-4-pyridin-3-yl-[1,3]dioxan-5-yl}-hex-4-enoic acid methyl ester
  参考文献：
  名称：

  Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of [2-Substituted-4-(3-pyridyl)-1,3-dioxan-5-yl]alkenoic Acids

  摘要：

  The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.

  DOI：

  10.1021/jm00004a014
• 作为产物：
  描述：

  甲醇 、 4(Z)-6-cis-<2,2-dimethyl-4-(3-pyridyl)-1,3-dioxan-5-yl>hexenoic acid 在 对甲苯磺酸 作用下， 反应 4.0h， 以96%的产率得到methyl (Z,7R,8S)-8-hydroxy-7-(hydroxymethyl)-8-pyridin-3-yloct-4-enoate
  参考文献：
  名称：

  Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of [2-Substituted-4-(3-pyridyl)-1,3-dioxan-5-yl]alkenoic Acids

  摘要：

  The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.

  DOI：

  10.1021/jm00004a014

文献信息

• Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of [2-Substituted-4-(3-pyridyl)-1,3-dioxan-5-yl]alkenoic Acids
  作者：Alan W. Faull、Andrew G. Brewster、George R. Brown、Michael J. Smithers、Ruth Jackson

  DOI：10.1021/jm00004a014

  日期：1995.2

  The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.