(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde | 614763-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde
• 英文别名: (4aR,5S)-1-(4-fluorophenyl)-4a-methyl-5,6,7,8-tetrahydro-4H-benzo[f]indazole-5-carbaldehyde
• CAS: 614763-01-8
• 化学式: C₁₉H₁₉FN₂O
• 分子量: 310.371
• InChiKey: XHGCSJVRTPIJCE-BEFAXECRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以51%的产率得到((4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl)methanol
  参考文献：
  名称：

  Stereoisomers of an Aryl Pyrazole Glucocorticoid Receptor Agonist Scaffold Elicit Differing Anti-inflammatory Responses

  摘要：

  DOI：

  10.1021/acsmedchemlett.2c00299
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 反应 36.0h， 以69%的产率得到(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde
  参考文献：
  名称：

  Stereoisomers of an Aryl Pyrazole Glucocorticoid Receptor Agonist Scaffold Elicit Differing Anti-inflammatory Responses

  摘要：

  DOI：

  10.1021/acsmedchemlett.2c00299

文献信息

• Novel <i>N-</i>Arylpyrazolo[3,2-<i>c</i>]-Based Ligands for the Glucocorticoid Receptor:  Receptor Binding and in Vivo Activity
  作者：Amjad Ali、Christopher F. Thompson、James M. Balkovec、Donald W. Graham、Milton L. Hammond、Nazia Quraishi、James R. Tata、Monica Einstein、Lan Ge、Georgianna Harris、Terri M. Kelly、Paul Mazur、Shilpa Pandit、Joseph Santoro、Ayesha Sitlani、Chuanlin Wang、Joanne Williamson、Douglas K. Miller、Chris M. Thompson、Dennis M. Zaller、Michael J. Forrest、Ester Carballo-Jane、Silvi Luell

  DOI：10.1021/jm030585i

  日期：2004.5.1

  A novel series of selective ligands for the human glucocorticoid receptor (hGR) are described. Preliminary structure-activity relationships were focused on substitution at C-1 and indicated a preference for 3-, 4-, and 5-substituted aromatic and benzylic groups. The resulting analogues, e.g., 18 and 34, exhibited excellent affinity for hGR (IC50 1.9 nM and 2.8 PM, respectively) and an interesting partial agonist profile in functional assays of transactivation (tyrosine aminotransferase, TAT, and glutamine synthetase, GS) and transrepression (IL-6). The most potent compounds described in this study were the tertiary alcohol derivatives 21 and 25. These candidates showed highly efficacious IL-6 inhibition versus dexamethasone. The thiophenyl analogue 25 was evaluated in vivo in the mouse LPS challenge model and showed an ED50 = 4.0 mg/kg, compared to 0.5 mg/kg for prednisolone in the same assay.
• Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy
  作者：Christopher F. Thompson、Nazia Quraishi、Amjad Ali、James R. Tata、Milton L. Hammond、James M. Balkovec、Monica Einstein、Lan Ge、Georgianna Harris、Theresa 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.2005.02.009

  日期：2005.4

  A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse. (c) 2005 Elsevier Ltd. All rights reserved.
• 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