(S)-2-(2,4-dichlorophenyl)-4-methyl-7-propyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene | 866141-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-2-(2,4-dichlorophenyl)-4-methyl-7-propyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene
• 英文别名: (10S)-3-(2,4-dichlorophenyl)-6-methyl-10-propyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
• CAS: 866141-43-7
• 化学式: C₁₈H₁₈Cl₂N₄
• 分子量: 361.274
• InChiKey: NECDAICTSIRDQF-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-(2,4-dichlorophenyl)-4-methyl-7-propyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene 、 溴甲基环丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 以55%的产率得到(10S)-9-(cyclopropylmethyl)-3-(2,4-dichlorophenyl)-6-methyl-10-propyl-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
• 作为产物：
  描述：

  2,2',4'-三氯苯乙酮 在 盐酸肼 、 氢溴酸 、 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 为溶剂， 反应 61.5h， 生成 (S)-2-(2,4-dichlorophenyl)-4-methyl-7-propyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene
  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