4α-isocyanato-11β,15β-dihydroxykaur-16-ene | 1391633-67-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4α-isocyanato-11β,15β-dihydroxykaur-16-ene
• 英文别名: (1R,4S,5R,9R,10S,11S,13S,15R)-5-isocyanato-5,9-dimethyl-14-methylidenetetracyclo[11.2.1.01,10.04,9]hexadecane-11,15-diol
• CAS: 1391633-67-2
• 化学式: C₂₀H₂₉NO₃
• 分子量: 331.455
• InChiKey: VZWILMSDGUSPQS-OFRYCBQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  69.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4α-isocyanato-11β,15β-dihydroxykaur-16-ene 、 叔丁胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以99%的产率得到N-(tert-butyl)-N-(11β,15β-dihydroxykaur-16-ene-4α-yl)urea
  参考文献：
  名称：

  Discovery and structure–activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: Potential impact in diabetes

  摘要：

  The biological screening of a collection of nature occurring diterpenoids against 11 beta-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11 beta-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11 beta-HSD1) = 9.4 nM and selectivity index (human 11 beta-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11 beta-HSD1 were generated using docking simulations. Based on the results, the structural activity relationships (SARs) of compounds 1b and 2 were also discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.010
• 作为产物：
  描述：

  叠氮磷酸二苯酯 、 ent-11α,15α-Dihydroxykaur-16-en-19-oic acid 在 三乙胺 作用下， 反应 1.5h， 以100%的产率得到4α-isocyanato-11β,15β-dihydroxykaur-16-ene
  参考文献：
  名称：

  Discovery and structure–activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: Potential impact in diabetes

  摘要：

  The biological screening of a collection of nature occurring diterpenoids against 11 beta-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11 beta-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11 beta-HSD1) = 9.4 nM and selectivity index (human 11 beta-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11 beta-HSD1 were generated using docking simulations. Based on the results, the structural activity relationships (SARs) of compounds 1b and 2 were also discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.010