methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate | 1297284-50-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate
• 英文别名: methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate；methyl 2-[3-[(3-benzyl-4-oxophthalazin-1-yl)methyl]-5-chloro-2-methylindol-1-yl]acetate
• CAS: 1297284-50-4
• 化学式: C₂₈H₂₄ClN₃O₃
• 分子量: 485.97
• InChiKey: MGQKCVIKXNSHKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  63.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 以55%的产率得到2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetic acid
  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
• 作为产物：
  描述：

  5-氯-2-甲基吲哚 在 正丁基锂 、 水 、 sodium acetate 、 potassium carbonate 、 lithium hydroxide 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 51.27h， 生成 methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate
  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

文献信息

• [EN] INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS CRTH2 À BASE D'INDOLE
  申请人：WYETH LLC

  公开号：WO2011055270A1

  公开（公告）日：2011-05-12

  Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.