4-amino-3,5-dichloro-N-(9-hydroxy-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethanobenzo[9]annulen-7-yl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-3,5-dichloro-N-(9-hydroxy-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethanobenzo[9]annulen-7-yl)benzamide
• 英文别名: 4-amino-3,5-dichloro-N-(12-hydroxy-10-tetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trienyl)benzamide
• 化学式: C₂₂H₂₂Cl₂N₂O₂
• 分子量: 417.335
• InChiKey: BBNDTOIDGWCRHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-amino-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-ol 、 4-氨基-3,5-二氯苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4-amino-3,5-dichloro-N-(9-hydroxy-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethanobenzo[9]annulen-7-yl)benzamide
  参考文献：
  名称：

  Searching for novel applications of the benzohomoadamantane scaffold in medicinal chemistry: Synthesis of novel 11β-HSD1 inhibitors

  摘要：

  The structural and physicochemical properties of the adamantane nucleus account for its use as a chemical scaffold in multiple drugs. In the last years, we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As adamantane is a common structural feature in several 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitors, we have explored the ability of the 6,7,8,9,10,11-hexahydro-5H-5,9: 7,11-dimethanobenzo[9]annulen-7-yl scaffold to act as a surrogate of the adamantane nucleus in a novel series of 11 beta-HSD1 inhibitors. Of note, within this family of compounds one derivative is endowed with submicromolar 11 beta-HSD1 inhibitory activity. Molecular modeling studies support the binding of the compounds to the active site of the enzyme. However, a fine tuning of the hydrophobicity of the size-expanded nucleus may be beneficial for the inhibitory potency. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.004