4-(1-Oxo-4-pyridin-3-ylphthalazin-2-yl)butanoic acid | 137381-92-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(1-Oxo-4-pyridin-3-ylphthalazin-2-yl)butanoic acid
• CAS: 137381-92-1
• 化学式: C₁₇H₁₅N₃O₃
• 分子量: 309.324
• InChiKey: TWAUMQQSPXJBGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  异丙胺 、 4-(1-Oxo-4-pyridin-3-ylphthalazin-2-yl)butanoic acid 在 五氯化磷 、 三乙胺 作用下， 生成 2-<3-<(N-isopropylamino)carbonyl>propyl>-4-(3-pyridyl)-1(2H)-phthalazinone
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones

  摘要：

  A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A(2) (TXA(2)) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated. While the length and the built of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b. These findings suggest that heteroaromatic nuclei at the Li-position of phthalazinones play a critical role in TXA(2) synthetase inhibition, Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity. These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1 (2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies. Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.

  DOI：

  10.1021/jm00077a009
• 作为产物：
  描述：

  1-hydroxy-4-(3-pyridyl)phthalazine 在 sodium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 生成 4-(1-Oxo-4-pyridin-3-ylphthalazin-2-yl)butanoic acid
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones

  摘要：

  A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A(2) (TXA(2)) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated. While the length and the built of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b. These findings suggest that heteroaromatic nuclei at the Li-position of phthalazinones play a critical role in TXA(2) synthetase inhibition, Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity. These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1 (2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies. Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.

  DOI：

  10.1021/jm00077a009

文献信息

• Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones
  作者：Masahisa Yamaguchi、Kenshi Kamei、Takaki Koga、Michitaka Akima、Akinori Maruyama、Toshio Kuroki、Nobuhiro Ohi

  DOI：10.1021/jm00077a009

  日期：1993.12

  A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A(2) (TXA(2)) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated. While the length and the built of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b. These findings suggest that heteroaromatic nuclei at the Li-position of phthalazinones play a critical role in TXA(2) synthetase inhibition, Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity. These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1 (2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies. Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.