2-(3-(3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetonitrile | 1297284-06-0

• 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: 2-(3-(3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetonitrile
• 英文别名: 2-(3-(3-Benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)-acetonitrile；2-[3-(3-benzyl-4-oxophthalazin-1-yl)-2-methylindol-1-yl]acetonitrile
• CAS: 1297284-06-0
• 化学式: C₂₆H₂₀N₄O
• 分子量: 404.471
• InChiKey: MTJCQSMLMLOCND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  61.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-(3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetonitrile 在 sodium azide 、 zinc dibromide 作用下， 以 水 、 异丙醇 为溶剂， 以46%的产率得到4-(1-((2H-tetrazol-5-yl)methyl)-2-methyl-1H-indol-3-yl)-2-benzylphthalazin-1(2H)-one
  参考文献：
  名称：

  INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS

  摘要：

  公开的是以下化合物的结构（I）：这些化合物可用作CRTH2受体的拮抗剂。还公开了含有化合物（I）的药物组合物以及利用化合物（I）治疗对抑制内源配体与CRTH2受体结合响应的疾病或疾病的用途。进一步描述了制备和使用这些化合物的方法。

  公开号：

  US20110105509A1
• 作为产物：
  描述：

  1-chloro-4-(2-methyl-1H-indol-3-yl)phthalazine 在 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2-(3-(3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetonitrile
  参考文献：
  名称：

  Diazine Indole Acetic Acids as Potent, Selective, and Orally Bioavailable Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents, 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.

  DOI：

  10.1021/jm300007n