1-[4-[(10S)-9-(cyclopropylmethyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl]-3-(trifluoromethyl)phenyl]ethanone | 866141-78-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-[(10S)-9-(cyclopropylmethyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl]-3-(trifluoromethyl)phenyl]ethanone
• CAS: 866141-78-8
• 化学式: C₂₄H₂₅F₃N₄O
• 分子量: 442.484
• InChiKey: IGJOCDFZJSWBAL-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  51
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[4-[(10S)-9-(cyclopropylmethyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl]-3-(trifluoromethyl)phenyl]ethanone 在 platinum(II) oxide 氢气 、 magnesium sulfate 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 20.0~60.0 ℃ 、275.79 kPa 条件下， 反应 19.5h， 生成 (10S)-9-(cyclopropylmethyl)-10-ethyl-6-methyl-3-[4-propan-2-yl-2-(trifluoromethyl)phenyl]-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 barium dihydroxide 、 四(三苯基膦)钯 、 氢溴酸 、 溴 、 sodium hydride 、 sodium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 89.75h， 生成 1-[4-[(10S)-9-(cyclopropylmethyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl]-3-(trifluoromethyl)phenyl]ethanone
  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