4-amino-8-bromo-N-cyclopropyl-7-fluorocinnoline-3-carboxamide | 1309764-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-amino-8-bromo-N-cyclopropyl-7-fluorocinnoline-3-carboxamide
• CAS: 1309764-51-9
• 化学式: C₁₂H₁₀BrFN₄O
• 分子量: 325.14
• InChiKey: PMOVIOFCWIBLQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 4-amino-8-bromo-N-cyclopropyl-7-fluorocinnoline-3-carboxamide 以 甲醇 为溶剂， 以81%的产率得到4-amino-8-bromo-N-cyclopropyl-7-fluorocinnoline-3-carboxamide methanesulfonic acid salt
  参考文献：
  名称：

  [EN] CINNOLINE COMPOUNDS, THEIR PREPARATION, AND THEIR USE
  [FR] COMPOSÉS DE CINNOLINE, LEUR PRÉPARATION ET LEUR UTILISATION

  摘要：

  本发明涉及茜草啉化合物，特别是4-氨基-N-环丙基-7-氟-8-(3,6-二甲氧吡啶并[4,5]嘧啶-4-基)茜草啉-3-羧酰胺及其盐。所述发明还涉及包含该化合物的组合物，以及用于生产该化合物的用途和过程。所述茜草啉化合物是GABAA调节剂，在治疗焦虑症、认知障碍、情绪障碍、精神分裂症和疼痛方面有用。

  公开号：

  WO2011021979A1
• 作为产物：
  描述：

  2-氰基-N-环丙基乙酰胺 在 盐酸 、 aluminum (III) chloride 、 溶剂黄146 作用下， 以 水 、 甲苯 为溶剂， 反应 21.67h， 生成 4-amino-8-bromo-N-cyclopropyl-7-fluorocinnoline-3-carboxamide
  参考文献：
  名称：

  [EN] CINNOLINE COMPOUNDS, THEIR PREPARATION, AND THEIR USE
  [FR] COMPOSÉS DE CINNOLINE, LEUR PRÉPARATION ET LEUR UTILISATION

  摘要：

  本发明涉及茜草啉化合物，特别是4-氨基-N-环丙基-7-氟-8-(3,6-二甲氧吡啶并[4,5]嘧啶-4-基)茜草啉-3-羧酰胺及其盐。所述发明还涉及包含该化合物的组合物，以及用于生产该化合物的用途和过程。所述茜草啉化合物是GABAA调节剂，在治疗焦虑症、认知障碍、情绪障碍、精神分裂症和疼痛方面有用。

  公开号：

  WO2011021979A1

文献信息

• Development and SAR of functionally selective allosteric modulators of GABAA receptors
  作者：Cristobal Alhambra、Chris Becker、Timothy Blake、Amy (Hui-Fang) Chang、James R. Damewood、Thalia Daniels、Bruce T. Dembofsky、David A. Gurley、James E. Hall、Keith J. Herzog、Carey L. Horchler、Cyrus J. Ohnmacht、Richard Jon Schmiesing、Adam Dudley、Maria D. Ribadeneira、Katherine S. Knappenberger、Carla Maciag、Mark M. Stein、Maninder Chopra、Xiaodong F. Liu、Edward P. Christian、Jeffrey L. Arriza、Marc J. Chapdelaine

  DOI：10.1016/j.bmc.2011.03.035

  日期：2011.5

  Positive modulators at the benzodiazepine site of alpha 2- and alpha 3-containing GABA(A) receptors are believed to be anxiolytic. Through oocyte voltage clamp studies, we have discovered two series of compounds that are positive modulators at alpha 2-/alpha 3-containing GABA(A) receptors and that show no functional activity at alpha 1-containing GABAA receptors. We report studies to improve this functional selectivity and ultimately deliver clinical candidates. The functional SAR of cinnolines and quinolines that are positive allosteric modulators of the alpha 2- and alpha 3-containing GABA(A) receptors, while simultaneously neutral antagonists at alpha 1-containing GABAA receptors, is described. Such functionally selective modulators of GABA(A) receptors are expected to be useful in the treatment of anxiety and other psychiatric illnesses. (C) 2011 Elsevier Ltd. All rights reserved.
• Developing dual functional allosteric modulators of GABAA receptors
  作者：Xiaodong F. Liu、Hui-Fang Chang、Richard Jon Schmiesing、Steven S. Wesolowski、Katharine S. Knappenberger、Jeffrey L. Arriza、Marc J. Chapdelaine

  DOI：10.1016/j.bmc.2010.09.058

  日期：2010.12

  Positive modulators at benzodiazepine sites of alpha 2- and alpha 3-containing GABA(A) receptors are believed to be anxiolytic. Negative allosteric modulators of alpha 5-containing GABA(A) receptors enhance cognition. By oocyte two-electrode voltage clamp and subsequent structure-activity relationship studies, we discovered cinnoline and quinoline derivatives that were both positive modulators at alpha 2-/alpha 3-containing GABA(A) receptors and negative modulators at alpha 5-containing GABA(A) receptors. In addition, these compounds showed no functional activity at alpha 1-containing GABA(A) receptors. Such dual functional modulators of GABA(A) receptors might be useful for treating comorbidity of anxiety and cognitive impairments in neurological and psychiatric illnesses. (C) 2010 Elsevier Ltd. All rights reserved.