9-Cyclohexyl-3-(2,4-dichlorophenyl)-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 9-Cyclohexyl-3-(2,4-dichlorophenyl)-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
• 化学式: C₂₁H₂₂Cl₂N₄
• 分子量: 401.338
• InChiKey: YVDHAPQBQNWZAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,2',4'-三氯苯乙酮 在 盐酸肼 、 potassium carbonate 、 对甲苯磺酸 、 一水合肼 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二苯醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 丁酮 为溶剂， 反应 76.5h， 生成 9-Cyclohexyl-3-(2,4-dichlorophenyl)-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
  参考文献：
  名称：

  Design and Synthesis of Tricyclic Corticotropin-Releasing Factor-1 Antagonists

  摘要：

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF, antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship between structure and CRF, binding affinity, NBI 35965 (12a) was identified as a high-affinity antagonist with a pK(i) value of 8.5. Compound 12a proved to be a functional CRF, antagonist with pIC(50) values of 7.1 and 6.9 in the in vitro CRF-stimulated cAMP accumulation and ACTH production assays, respectively, and 12a also reduced CRF or stress induced ACTH production in vivo.

  DOI：

  10.1021/jm049085v

文献信息

• Design and Synthesis of Tricyclic Corticotropin-Releasing Factor-1 Antagonists
  作者：Raymond S. Gross、Zhiqiang Guo、Brian Dyck、Tim Coon、Charles Q. Huang、Richard F. Lowe、Dragan Marinkovic、Manisha Moorjani、Jodene Nelson、Said Zamani-Kord、Dimitri E. Grigoriadis、Sam R. J. Hoare、Paul D. Crowe、Jane Han Bu、Mustapha Haddach、James McCarthy、John Saunders、Robert Sullivan、Chen、John P. Williams

  DOI：10.1021/jm049085v

  日期：2005.9.1

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF, antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship between structure and CRF, binding affinity, NBI 35965 (12a) was identified as a high-affinity antagonist with a pK(i) value of 8.5. Compound 12a proved to be a functional CRF, antagonist with pIC(50) values of 7.1 and 6.9 in the in vitro CRF-stimulated cAMP accumulation and ACTH production assays, respectively, and 12a also reduced CRF or stress induced ACTH production in vivo.