(R)-8a-benzyl-2-(4-tert-butyl-benzenesulfonyl)-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one | 864973-54-6

• 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: (R)-8a-benzyl-2-(4-tert-butyl-benzenesulfonyl)-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one
• 英文别名: (R)-8a-benzyl-2-(4-tert-butylphenylsulfonyl)-1,2,3,4,8,8a-hexahydroisoquinolin-6(7H)-one；(8aR)-8a-benzyl-2-(4-tert-butylphenyl)sulfonyl-3,4,7,8-tetrahydro-1H-isoquinolin-6-one
• CAS: 864973-54-6
• 化学式: C₂₆H₃₁NO₃S
• 分子量: 437.603
• InChiKey: YGAPRLXEVVTMID-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-8a-benzyl-2-(4-tert-butyl-benzenesulfonyl)-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one 、 甲酸乙酯 在 sodium methylate 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 (S)-8a-benzyl-2-(4-tert-butyl-benzenesulfonyl)-7-[1-hydroxy-meth-(Z)-ylidene]-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one
  参考文献：
  名称：

  [EN] FUSED RING AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  [FR] MODULATEURS DE RECEPTEURS GLUCOCORTICOIDES D'AZADECALINE A CYCLES ACCOLES

  摘要：

  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。

  公开号：

  WO2005087769A1
• 作为产物：
  描述：

  对叔丁基苯磺酰氯 、 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (R)-8a-benzyl-2-(4-tert-butyl-benzenesulfonyl)-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one
  参考文献：
  名称：

  [EN] FUSED RING AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  [FR] MODULATEURS DE RECEPTEURS GLUCOCORTICOIDES D'AZADECALINE A CYCLES ACCOLES

  摘要：

  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。

  公开号：

  WO2005087769A1

文献信息

• 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。
• 2-Benzenesulfonyl-8a-benzyl-hexahydro-2H-isoquinolin-6-ones as selective glucocorticoid receptor antagonists
  作者：Robin D. Clark、Nicholas C. Ray、Paul Blaney、Peter H. Crackett、Christopher Hurley、Karen Williams、Hazel J. Dyke、David E. Clark、Peter M. Lockey、Rene Devos、Melanie Wong、Anne White、Joseph K. Belanoff

  DOI：10.1016/j.bmcl.2007.07.055

  日期：2007.10

  The 2-azadecalin ring system was evaluated as a scaffold for the preparation of glucocorticoid receptor (GR) antagonists. High affinity, selective GR antagonists were discovered based on a hypothetical binding mode related to the steroidal GR antagonist RU-43044. 2-Benzenesulfonyl substituted 8a-benzyl-hexahydro-2H-isoquinolin-6-ones exemplified by (R)-37 had low nanomolar affinity for GR with moderate functional activity (200 nM) in a reporter gene assay. These compounds were devoid of affinity for other steroidal receptors (ER, AR, MR, and PR). Analogues based on an alternative putative binding mode (CP-like) were found to be inactive. (c) 2007 Elsevier Ltd. All rights reserved.
• 1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as selective glucocorticoid receptor antagonists with high functional activity
  作者：Robin D. Clark、Nicholas C. Ray、Karen Williams、Paul Blaney、Stuart Ward、Peter H. Crackett、Christopher Hurley、Hazel J. Dyke、David E. Clark、Peter Lockey、Rene Devos、Melanie Wong、Soraya S. Porres、Colin P. Bright、Robert E. Jenkins、Joseph Belanoff

  DOI：10.1016/j.bmcl.2008.01.027

  日期：2008.2

  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.
• US7928237B2
  申请人：——

  公开号：US7928237B2

  公开（公告）日：2011-04-19