methyl 2-[3-(1-benzyl-2-oxo-3H-1,4-benzodiazepin-5-yl)-4-methoxyphenyl]acetate | 721948-31-8

• 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: methyl 2-[3-(1-benzyl-2-oxo-3H-1,4-benzodiazepin-5-yl)-4-methoxyphenyl]acetate
• CAS: 721948-31-8
• 化学式: C₂₆H₂₄N₂O₄
• 分子量: 428.488
• InChiKey: ZYOFSPGTPPSOSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-[3-(1-benzyl-2-oxo-3H-1,4-benzodiazepin-5-yl)-4-methoxyphenyl]acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以90%的产率得到2-(3-(1-benzyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-4-methoxyphenyl)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
• 作为产物：
  描述：

  4-甲氧基苯乙酸甲酯 在 吡啶 、 aluminum (III) chloride 、 potassium tert-butylate 、 铁粉 、 溶剂黄146 作用下， 以 1,1-二氯乙烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 methyl 2-[3-(1-benzyl-2-oxo-3H-1,4-benzodiazepin-5-yl)-4-methoxyphenyl]acetate
  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

• Asthma and allergic inflammation modulators
  申请人：Fu Zice

  公开号：US20080085891A1

  公开（公告）日：2008-04-10

  Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related diseases and conditions. In particular, the invention provides compounds which modulate the function and/or expression of proteins involved in atopic diseases, inflammatory conditions and cancer. The subject compounds are carboxylic acid derivatives.

  本发明提供了在治疗炎症和免疫相关疾病和病况方面有用的化合物、制药组合物和方法。特别是，本发明提供了调节参与过敏性疾病、炎症病况和癌症的蛋白质的功能和/或表达的化合物。所述化合物为羧酸衍生物。
• US7321001B2
  申请人：——

  公开号：US7321001B2

  公开（公告）日：2008-01-22
• US7541383B2
  申请人：——

  公开号：US7541383B2

  公开（公告）日：2009-06-02
• 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.