4-pyridin-4-yl-2H-phthalazin-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-pyridin-4-yl-2H-phthalazin-1-one
• 化学式: C₁₃H₉N₃O
• 分子量: 223.234
• InChiKey: SDEPPVQXYSHWPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-pyridin-4-yl-2H-phthalazin-1-one 在 sodium hydride 、 sodium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-[3-[1-[3-(1-oxo-4-pyridin-4-ylphthalazin-2-yl)propyl]piperidin-4-yl]phenyl]acetamide
  参考文献：
  名称：

  4-Heteroaryl Phthalazin-1(2H)-one Derivatives as Potent Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists

  摘要：

  DOI：

  10.5012/bkcs.2012.33.7.2389
• 作为产物：
  描述：

  4-溴吡啶 在 正丁基锂 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.5h， 生成 4-pyridin-4-yl-2H-phthalazin-1-one
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)-phthalazinones

  摘要：

  A number of 4-substituted 2-[omega-(1-imidazolyl)allryl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.

  DOI：

  10.1021/jm00077a008

文献信息

• Application of Organolithium and Related Reagents in Synthesis. Part 22¹. Synthetic Strategies Based on Ortho-Aromatic Metallation. A Concise Regiospecific Conversion of Benzoic Acids into the 4-Pyridyl-2<i>H</i>-Phthalazin-1-Ones
  作者：J. Z. Brzezinski、J. Epsztajn、A. D. Bakalarz、A. Lajszczak、Z. Malinowski

  DOI：10.1080/00397919908085788

  日期：1999.2

  Abstract The synthesis of phthalazin-1-ones 6, 7, 8 via the reaction of 3-hydroxyisoindolin-l-ones 3, 4, 5 with hydrazine hydrate is described. Starting compounds 3, 4, 5 were regiospecifically prepared upon the lithiation (n-BuLi) of the benzanilides 1 and subsequently the reaction of the dilithiated anilides 2 with methyl pyridinecarboxylates.

  摘要 描述了通过 3-羟基异吲哚啉-1-酮 3、4、5 与水合肼反应合成酞嗪-1-酮 6、7、8。起始化合物 3、4、5 在苯甲酰苯胺 1 的锂化 (n-BuLi) 和随后二锂化的苯胺 2 与吡啶羧酸甲酯反应后进行区域特异性制备。
• Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives
  作者：Tatsuzo Ukita、Masakatsu Sugahara、Yoshihiro Terakawa、Tooru Kuroda、Kazuteru Wada、Aya Nakata、Yasushi Ohmachi、Hideo Kikkawa、Katsuo Ikezawa、Kazuaki Naito

  DOI：10.1021/jm980314l

  日期：1999.3.1

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).
• Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)-phthalazinones
  作者：Masahisa Yamaguchi、Kenshi Kamei、Takaki Koga、Michitaka Akima、Toshio Kuroki、Nobuhiro Ohi

  DOI：10.1021/jm00077a008

  日期：1993.12

  A number of 4-substituted 2-[omega-(1-imidazolyl)allryl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
• 4-Heteroaryl Phthalazin-1(2H)-one Derivatives as Potent Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists
  作者：Chae-Jo Lim、Ka-Eun Lee、Byung-Ho Lee、Kwang-Seok Oh、Kyu-Yang Yi

  DOI：10.5012/bkcs.2012.33.7.2389

  日期：2012.7.20