5-[2-methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[2-methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole
• 英文别名: PDE472；5-(2-methoxy-5-pyridin-4-ylphenyl)-2,1,3-benzoxadiazole
• 化学式: C₁₈H₁₃N₃O₂
• 分子量: 303.32
• InChiKey: UGCRBILAPBGGAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[2-methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole 、 顺丁烯二酸 以 四氢呋喃 为溶剂， 反应 0.58h， 以98%的产率得到5-[2-methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole hemi-maleate salt
  参考文献：
  名称：

  Large-Scale Negishi Coupling as Applied to the Synthesis of PDE472, an Inhibitor of Phosphodiesterase Type 4D

  摘要：

  5-[2-Methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole (PDE472) is a selective inhibitor of the phosphodiesterase PDE4D isoenzyme, which is a recognised drug target for the treatment of asthma. Different synthetic routes to PDE472 were investigated, and the research synthesis was optimised to prepare a phase I batch on pilot-plant scale with the focus on the elimination or minimization of inherent process risks. An important refinement of the key Negishi aryl-aryl coupling involved preforming the arylpalladium complex, which was then added to the arylzinc intermediate. Residual palladium was removed from PDE472 via crystallization of the hemi-maleate salt, which afforded drug-substance containing < 2 ppm Pd.

  DOI：

  10.1021/op025615q
• 作为产物：
  描述：

  4-氯吡啶 在 四(三苯基膦)钯 、 溴 、 碘 、 正己基锂 、 magnesium 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 84.0h， 生成 5-[2-methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole
  参考文献：
  名称：

  Large-Scale Negishi Coupling as Applied to the Synthesis of PDE472, an Inhibitor of Phosphodiesterase Type 4D

  摘要：

  5-[2-Methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole (PDE472) is a selective inhibitor of the phosphodiesterase PDE4D isoenzyme, which is a recognised drug target for the treatment of asthma. Different synthetic routes to PDE472 were investigated, and the research synthesis was optimised to prepare a phase I batch on pilot-plant scale with the focus on the elimination or minimization of inherent process risks. An important refinement of the key Negishi aryl-aryl coupling involved preforming the arylpalladium complex, which was then added to the arylzinc intermediate. Residual palladium was removed from PDE472 via crystallization of the hemi-maleate salt, which afforded drug-substance containing < 2 ppm Pd.

  DOI：

  10.1021/op025615q

文献信息

• Phenylpyridine derivatives useful as phosphodiesterase inhibitors
  申请人：——

  公开号：US20020028831A1

  公开（公告）日：2002-03-07

  (4-oxy-3-(aryl)phenyl)pyridine compounds, in free or acid addition salt form, are useful as pharmaceuticals for treatment and prophylaxis of inflammation, particularly inflammatory or obstructive diseases of the airways, e.g. for asthma therapy. Preferred compounds are novel biphenyl pyridines, biphenyl benzamides and biphenyl phenylcarboxy compounds. The compounds are selective inhibitors of PDE 4 isoenzyme activity and also act to down regulate or inhibit TNF-&agr; release.

  (4-氧代-3-(芳基)苯基)吡啶化合物，以自由形式或酸盐形式，作为药物用于治疗和预防炎症，特别是空气道的炎症或阻塞性疾病，例如哮喘治疗。优选的化合物是新型的联苯基吡啶、联苯基苯甲酰胺和联苯基苯基羧酸化合物。这些化合物是PDE 4同工酶活性的选择性抑制剂，同时也可以下调或抑制TNF-α的释放。
• US6090817A
  申请人：——

  公开号：US6090817A

  公开（公告）日：2000-07-18
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  公开号：US6258843B1

  公开（公告）日：2001-07-10
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  申请人：——

  公开号：US6410547B1

  公开（公告）日：2002-06-25