4-amino-N-cyclopropyl-7-fluoro-8-(3,6-dimethoxypyridazin-4-yl)cinnoline-3-carboxamide | 1268518-42-8

• 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-N-cyclopropyl-7-fluoro-8-(3,6-dimethoxypyridazin-4-yl)cinnoline-3-carboxamide
• 英文别名: 4-amino-N-cyclopropyl-8-(3,6-dimethoxypyridazin-4-yl)-7-fluorocinnoline-3-carboxamide
• CAS: 1268518-42-8
• 化学式: C₁₈H₁₇FN₆O₃
• 分子量: 384.37
• InChiKey: KJDDJAPSHCVDDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氰基-N-环丙基乙酰胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 tri tert-butylphosphoniumtetrafluoroborate 盐酸 、 aluminum (III) chloride 、 potassium fluoride 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 2.5h， 生成 4-amino-N-cyclopropyl-7-fluoro-8-(3,6-dimethoxypyridazin-4-yl)cinnoline-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

• [EN] CINNOLINE COMPOUNDS, THEIR PREPARATION, AND THEIR USE<br/>[FR] COMPOSÉS DE CINNOLINE, LEUR PRÉPARATION ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2011021979A1

  公开（公告）日：2011-02-24

  The present invention relates to cinnoline compounds, particularly 4-amino-N-cyclopropyl- 7-fluoro-8-(3,6-dimethoxypyridazin-4-yl)cinnoline-3-carboxamide and salts thereof. The claimed invention also relates to compositions comprising such a compound, as well as uses of and processes for production of said compounds. The claimed cinnoline compounds are GABAA modulators useful in the treatment of anxiety disorders, cognitive disorders, mood disorders, schizophrenia and pain.

  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。
• 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.