7-[4-[4-[[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]methyl]phenyl]triazol-1-yl]heptanoic acid | 1431473-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-[4-[4-[[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]methyl]phenyl]triazol-1-yl]heptanoic acid
• CAS: 1431473-53-8
• 化学式: C₄₂H₆₂N₄O₇Si
• 分子量: 763.062
• InChiKey: XAGURDIYRYGSSG-JKZGQAOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.86
• 重原子数：
  54
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-[4-[4-[[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]methyl]phenyl]triazol-1-yl]heptanoic acid 在 氯甲酸乙酯 、 三乙胺 、 盐酸羟胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.42h， 以511 mg的产率得到(4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(4-{ 1-[7-(hydroxyamino)-7-oxoheptyl]-1H-1,2,3-triazol-4-yl}benzyl)carbamoyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one
  参考文献：
  名称：

  Design and Synthesis of Dual-Action Inhibitors Targeting Histone Deacetylases and 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase for Cancer Treatment

  摘要：

  A series of dual-action compounds were designed to target histone deacetylase (HDAC) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) by having a hydroxamate group essential for chelation with the zinc ion in the active site of HDAC and the key structural elements of statin for binding with both proteins. In our study, the statin hydroxamic acids prepared by a fused strategy are most promising in cancer treatments. These compounds showed potent inhibitory activities against HDACs and HMGR with IC50 values in the nanomolar range. These compounds also effectively reduced the HMGR activity as well as promoted the acetylations of histone and tubulin in cancer cells, but were not toxic to normal cells.

  DOI：

  10.1021/jm400179b
• 作为产物：
  描述：

  洛伐他汀 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 54.0h， 生成 7-[4-[4-[[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]methyl]phenyl]triazol-1-yl]heptanoic acid
  参考文献：
  名称：

  Design and Synthesis of Dual-Action Inhibitors Targeting Histone Deacetylases and 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase for Cancer Treatment

  摘要：

  A series of dual-action compounds were designed to target histone deacetylase (HDAC) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) by having a hydroxamate group essential for chelation with the zinc ion in the active site of HDAC and the key structural elements of statin for binding with both proteins. In our study, the statin hydroxamic acids prepared by a fused strategy are most promising in cancer treatments. These compounds showed potent inhibitory activities against HDACs and HMGR with IC50 values in the nanomolar range. These compounds also effectively reduced the HMGR activity as well as promoted the acetylations of histone and tubulin in cancer cells, but were not toxic to normal cells.

  DOI：

  10.1021/jm400179b