(S)-6-cyclopropylmethyl-2-bromo-7-ethyl-4-methyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene | 866141-75-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: (S)-6-cyclopropylmethyl-2-bromo-7-ethyl-4-methyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene
• 英文别名: (10S)-3-bromo-9-(cyclopropylmethyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
• CAS: 866141-75-5
• 化学式: C₁₅H₁₉BrN₄
• 分子量: 335.247
• InChiKey: AKLMYGUEYCHBFO-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-6-cyclopropylmethyl-2-bromo-7-ethyl-4-methyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene 、 4-氯-2-甲基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以49%的产率得到(10S)-3-(4-chloro-2-methylphenyl)-9-(cyclopropylmethyl)-10-ethyl-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
• 作为产物：
  描述：

  7-氯-5-甲基-1H-吡唑并[4,3-b]-吡啶 在 氢溴酸 、 溴 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 89.75h， 生成 (S)-6-cyclopropylmethyl-2-bromo-7-ethyl-4-methyl-7,8-dihydro-6H-1,3,6,8a-tetraazaacenaphthylene 、 alkaline earth salt of/the/ methylsulfuric acid
  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.