(R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H-cyclopenta[f]indazol-5-yl](1-benzothiophen-3-yl)methanol | 614762-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H-cyclopenta[f]indazol-5-yl](1-benzothiophen-3-yl)methanol
• 英文别名: (R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,5,6,7-tetrahydrocyclopenta[f]indazol-5-yl]-(1-benzothiophen-3-yl)methanol
• CAS: 614762-03-7
• 化学式: C₂₆H₂₃FN₂OS
• 分子量: 430.546
• InChiKey: FJQOIKVDJJOXNL-RZFJZAQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H-cyclopenta[f]indazol-5-yl](1-benzothiophen-3-yl)methanol 在 间氯过氧苯甲酸 作用下， 以15%的产率得到(R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,5,6,7-tetrahydrocyclopenta[f]indazol-5-yl]-(1,1-dioxo-1-benzothiophen-3-yl)methanol
  参考文献：
  名称：

  Novel glucocorticoids containing a 6,5-bicyclic core fused to a pyrazole ring: Synthesis, in vitro profile, molecular modeling studies, and in vivo experiments

  摘要：

  Chemistry was developed to synthesize the title series of compounds. The ability of these novel ligands to bind to the glucocorticoid receptor was investigated. These compounds were also tested in a series of functional assays and some were found to display the profile of a dissociated glucocorticoid. The SAR of the 6,5-bicyclic series differed markedly from the previously reported 6,6-series. Molecular modeling studies were employed to understand the conformational differences between the two series of compounds, which may explain their divergent activity. Two compounds were profiled in vivo and shown to reduce inflammation in a mouse model. An active metabolite is suspected in one case. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.103
• 作为产物：
  描述：

  (4αS)-1-(4-fluorophenyl)-4α-methyl-4,4α,6,7-tetrahydrocyclopenta[f]indazol-5(1H)-one 在 9-borabicyclo[3.3.1]nonane dimer 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H-cyclopenta[f]indazol-5-yl](1-benzothiophen-3-yl)methanol
  参考文献：
  名称：

  Novel glucocorticoids containing a 6,5-bicyclic core fused to a pyrazole ring: Synthesis, in vitro profile, molecular modeling studies, and in vivo experiments

  摘要：

  Chemistry was developed to synthesize the title series of compounds. The ability of these novel ligands to bind to the glucocorticoid receptor was investigated. These compounds were also tested in a series of functional assays and some were found to display the profile of a dissociated glucocorticoid. The SAR of the 6,5-bicyclic series differed markedly from the previously reported 6,6-series. Molecular modeling studies were employed to understand the conformational differences between the two series of compounds, which may explain their divergent activity. Two compounds were profiled in vivo and shown to reduce inflammation in a mouse model. An active metabolite is suspected in one case. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.103

文献信息

• 1H-BENZO(F)INDAZOL-5-YL DERIVATIVES AS SELECTIVE GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1496892B1

  公开（公告）日：2011-01-26
• 1H-benzo[F]indazol-5-YL derivatives as selective glucocorticoid receptor modulators
  申请人：Ali Amjad

  公开号：US20080076795A1

  公开（公告）日：2008-03-27

  The present invention encompasses compounds of Formula I: or pharmaceutically acceptable salts or hydrates thereof, which are useful as selective glucocorticoid receptor ligands for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.
• US7282591B2
  申请人：——

  公开号：US7282591B2

  公开（公告）日：2007-10-16
• US7625937B2
  申请人：——

  公开号：US7625937B2

  公开（公告）日：2009-12-01
• Novel glucocorticoids containing a 6,5-bicyclic core fused to a pyrazole ring: Synthesis, in vitro profile, molecular modeling studies, and in vivo experiments
  作者：Christopher F. Thompson、Nazia Quraishi、Amjad Ali、Ralph T. Mosley、James R. Tata、Milton L. Hammond、James M. Balkovec、Monica Einstein、Lan Ge、Georgianna Harris、Terri M. Kelly、Paul Mazur、Shilpa Pandit、Joseph Santoro、Ayesha Sitlani、Chuanlin Wang、Joanne Williamson、Douglas K. Miller、Ting-ting D. Yamin、Chris M. Thompson、Edward A. O’Neill、Dennis Zaller、Michael J. Forrest、Ester Carballo-Jane、Silvi Luell

  DOI：10.1016/j.bmcl.2007.03.103

  日期：2007.6

  Chemistry was developed to synthesize the title series of compounds. The ability of these novel ligands to bind to the glucocorticoid receptor was investigated. These compounds were also tested in a series of functional assays and some were found to display the profile of a dissociated glucocorticoid. The SAR of the 6,5-bicyclic series differed markedly from the previously reported 6,6-series. Molecular modeling studies were employed to understand the conformational differences between the two series of compounds, which may explain their divergent activity. Two compounds were profiled in vivo and shown to reduce inflammation in a mouse model. An active metabolite is suspected in one case. (c) 2007 Elsevier Ltd. All rights reserved.