1-(4-fluorophenyl)-4a-[(4-fluorophenyl)methyl]-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-g]isoquinoline | 865062-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-fluorophenyl)-4a-[(4-fluorophenyl)methyl]-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-g]isoquinoline
• CAS: 865062-64-2
• 化学式: C₂₃H₂₁F₂N₃
• 分子量: 377.437
• InChiKey: KUWOLTWFWUDAOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴甲基吡啶 、 1-(4-fluorophenyl)-4a-[(4-fluorophenyl)methyl]-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-g]isoquinoline 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 4a-(4-fluoro-benzyl)-1-(4-fluoro-phenyl)-6-pyridin-3-ylmethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene
  参考文献：
  名称：

  1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as selective glucocorticoid receptor antagonists with high functional activity

  摘要：

  Addition of the 4-fluorophenylpyrazole group to the previously described 2-azadecalin glucocorticoid receptor (GR) antagonist 1 resulted in significantly enhanced functional activity. SAR of the bridgehead substituent indicated that whereas groups as small as methyl afforded high GR binding, GR functional activity was enhanced by larger groups such as benzyl, substituted ethers, and aminoalkyl derivatives. GR antagonists with binding and functional activity comparable to mifepristone were discovered ( e. g., 52: GR binding K-i 0.7 nM; GR reporter gene functional K-i 0.6 nM) and found to be highly selective over other steroid receptors. Analogues 43 and 45 had > 50% oral bioavailability in the dog. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.027
• 作为产物：
  描述：

  6-benzyl-4a-(4-fluoro-benzyl)-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-cyclopenta[b]naphthalene 在 甲醇 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 1-(4-fluorophenyl)-4a-[(4-fluorophenyl)methyl]-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-g]isoquinoline
  参考文献：
  名称：

  1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as selective glucocorticoid receptor antagonists with high functional activity

  摘要：

  Addition of the 4-fluorophenylpyrazole group to the previously described 2-azadecalin glucocorticoid receptor (GR) antagonist 1 resulted in significantly enhanced functional activity. SAR of the bridgehead substituent indicated that whereas groups as small as methyl afforded high GR binding, GR functional activity was enhanced by larger groups such as benzyl, substituted ethers, and aminoalkyl derivatives. GR antagonists with binding and functional activity comparable to mifepristone were discovered ( e. g., 52: GR binding K-i 0.7 nM; GR reporter gene functional K-i 0.6 nM) and found to be highly selective over other steroid receptors. Analogues 43 and 45 had > 50% oral bioavailability in the dog. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.027

文献信息

• [EN] FUSED RING AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RECEPTEURS GLUCOCORTICOIDES D'AZADECALINE A CYCLES ACCOLES
  申请人：CORCEPT THERAPEUTICS INC

  公开号：WO2005087769A1

  公开（公告）日：2005-09-22

  The present invention provides a novel class of fused ring azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了一种新型的融合环氮杂蒽类化合物，以及使用该化合物作为糖皮质激素受体调节剂的方法。
• Fused Ring Azadecalin Glucocorticoid Receptor Modulators
  申请人：Clark D. Robin

  公开号：US20070281928A1

  公开（公告）日：2007-12-06

  The present invention provides a novel class of fused ring azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了一种新型的融合环氮杂莰化合物，以及使用这些化合物作为糖皮质激素受体调节剂的方法。
• FUSED RING AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Clark Robin D.

  公开号：US20120225856A1

  公开（公告）日：2012-09-06

  The present invention provides a novel class of fused ring azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了一种新型的融合环氮杂癸烷化合物，以及使用该化合物作为糖皮质激素受体调节剂的方法。
• US7928237B2
  申请人：——

  公开号：US7928237B2

  公开（公告）日：2011-04-19
• US8557839B2
  申请人：——

  公开号：US8557839B2

  公开（公告）日：2013-10-15