2-(4-methoxy-3-(2-oxo-1-(4-(trifluoromethyl)benzyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)phenyl)acetic acid | 1292285-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2-(4-methoxy-3-(2-oxo-1-(4-(trifluoromethyl)benzyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)phenyl)acetic acid
• 英文别名: 2-[4-methoxy-3-[2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]-3H-1,4-benzodiazepin-5-yl]phenyl]acetic acid
• CAS: 1292285-00-7
• 化学式: C₂₆H₂₁F₃N₂O₄
• 分子量: 482.459
• InChiKey: FZQJQWGWGPOIFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 2-(4-methoxy-3-(2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)phenyl)acetate 在 potassium tert-butylate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2-(4-methoxy-3-(2-oxo-1-(4-(trifluoromethyl)benzyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)phenyl)acetic acid
  参考文献：
  名称：

  Benzodiazepinone Derivatives as CRTH2 Antagonists

  摘要：

  Multiple CRTH2 antagonists are currently evaluated in human clinical trials for asthma and chronic obstructive pulmonary disease (COPD). During our lead optimization for CRTH2 antagonists, an observation of an intramolecular hydrogen bond in ortho-phenylsulfonamido benzophenone derivatives led to the design and synthesis of conformationally constrained benzodiazepinones as potent CRTH2 antagonists. The benzodiazepinones are 2 orders of magnitude more potent than the original flexible bisaryl ethers in our binding assay. Selected benzodiazepinones, such as compound 6, were also potent in the human eosinophil shape change assay. Analysis of the rigid conformations of these benzodiazepinones and ortho-phenylsulfonamido benzophenones provided an explanation for the structure-activity relationship and revealed the possible bound conformations to CRTH2, which may be useful for building a pharmacophore model of CRTH2 antagonists.

  DOI：

  10.1021/ml200019y

文献信息

• Benzodiazepinone Derivatives as CRTH2 Antagonists
  作者：Jiwen (Jim) Liu、Alan C. Cheng、H. Lucy Tang、Julio C. Medina

  DOI：10.1021/ml200019y

  日期：2011.7.14

  Multiple CRTH2 antagonists are currently evaluated in human clinical trials for asthma and chronic obstructive pulmonary disease (COPD). During our lead optimization for CRTH2 antagonists, an observation of an intramolecular hydrogen bond in ortho-phenylsulfonamido benzophenone derivatives led to the design and synthesis of conformationally constrained benzodiazepinones as potent CRTH2 antagonists. The benzodiazepinones are 2 orders of magnitude more potent than the original flexible bisaryl ethers in our binding assay. Selected benzodiazepinones, such as compound 6, were also potent in the human eosinophil shape change assay. Analysis of the rigid conformations of these benzodiazepinones and ortho-phenylsulfonamido benzophenones provided an explanation for the structure-activity relationship and revealed the possible bound conformations to CRTH2, which may be useful for building a pharmacophore model of CRTH2 antagonists.