1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]ethanone | 694526-58-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]ethanone
• CAS: 694526-58-4
• 化学式: C₂₀H₂₁FN₂O
• 分子量: 324.398
• InChiKey: JVUMVCTWVZCJFH-QUCCMNQESA-N

反应信息

• 作为反应物：
  描述：

  甲基锂 、 1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]ethanone 以 乙醚 为溶剂， 反应 2.0h， 以56%的产率得到2-[(4aR,5S)-1-(4-Fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-propan-2-ol
  参考文献：
  名称：

  Novel N-Arylpyrazolo[3,2-c]-Based Ligands for the Glucocorticoid Receptor:  Receptor Binding and in Vivo Activity

  摘要：

  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.

  DOI：

  10.1021/jm030585i
• 作为产物：
  描述：

  (4aR)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hyxahydro-1H-benzo[f]indazole-5-carbaldehyde 在 N-甲基吲哚酮 、 四丙基高钌酸铵 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]ethanone
  参考文献：
  名称：

  Novel N-Arylpyrazolo[3,2-c]-Based Ligands for the Glucocorticoid Receptor:  Receptor Binding and in Vivo Activity

  摘要：

  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.

  DOI：

  10.1021/jm030585i