(4-fluorophenyl)[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]methanol | 1206515-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4-fluorophenyl)[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]methanol
• CAS: 1206515-72-1
• 化学式: C₂₅H₂₄F₂N₂O
• 分子量: 406.475
• InChiKey: YXQPDNYJXVGIES-PIHPCUNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.77
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.05
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4-fluorophenyl)[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]methanol 在 N-甲基吗啉氧化物 、 四丙基高钌酸铵 作用下， 以 二氯甲烷 为溶剂， 反应 2.58h， 以24 mg的产率得到(4-fluorophenyl)[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]methanone
  参考文献：
  名称：

  Novel Synthesis of the Hexahydroimidazo[1,5b]isoquinoline Scaffold: Application to the Synthesis of Glucocorticoid Receptor Modulators

  摘要：

  The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure - activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticold receptor (GR) in terms of binding affinity, although the partial agonist activity in the transrepressive assays depends on the substitution pattern on the B-ring. More importantly, most compounds in the HHII series bearing a tertiary alcohol moiety on the B-ring are either inactive or significantly less active in inducing GR-mediated transactivation, thus displaying a "dissociated" pharmacology in vitro.

  DOI：

  10.1021/jm901551w
• 作为产物：
  描述：

  在 碳酸氢钠 作用下， 以 水 为溶剂， 生成 (4-fluorophenyl)[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]methanol
  参考文献：
  名称：

  Novel Synthesis of the Hexahydroimidazo[1,5b]isoquinoline Scaffold: Application to the Synthesis of Glucocorticoid Receptor Modulators

  摘要：

  The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure - activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticold receptor (GR) in terms of binding affinity, although the partial agonist activity in the transrepressive assays depends on the substitution pattern on the B-ring. More importantly, most compounds in the HHII series bearing a tertiary alcohol moiety on the B-ring are either inactive or significantly less active in inducing GR-mediated transactivation, thus displaying a "dissociated" pharmacology in vitro.

  DOI：

  10.1021/jm901551w