(E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methyl-N-trityloxyhex-4-enamide | 1001329-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methyl-N-trityloxyhex-4-enamide
• CAS: 1001329-49-2
• 化学式: C₃₇H₃₇NO₆
• 分子量: 591.704
• InChiKey: XPMNZYWBTHNMLS-LKUDQCMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methyl-N-trityloxyhex-4-enamide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到(E)-6-(1,3-dihydro-4,6-dimethoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenohydroxamic acid
  参考文献：
  名称：

  Dual Inhibitors of Inosine Monophosphate Dehydrogenase and Histone Deacetylases for Cancer Treatment

  摘要：

  Mycophenolic acid (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used worldwide in transplantation. Recently, numerous studies showed its importance in cancer treatment. Consequently, MPA entered clinical trials in advanced multiple myeloma patients. Suberoylanilide hydroxamic acid (SAHA), a potent differentiation agent acting through inhibition of histone deacetylases (HDACs), was recently approved for treatment of cutaneous T cell lymphoma. We report herein the synthesis of dual inhibitors of IMPDH and HDACs. We found that mycophenolic hydroxamic acid (9, MAHA) inhibits both IMPDH (K-i = 30 nM) and HDAC (IC50 = 5.0 mu M). A modification of SAHA with groups known to interact with IMPDH afforded a SAHA analogue 14, which inhibits IMPDH (K-i = 1.7 mu M) and HDAC (IC50 = 0.06 mu M). Both MAHA (IC50 = 4.8 mu M) and SAHA analogue 14 (IC50 = 7.7 mu M) were more potent than parent compounds as antiproliferation agents. They were also significantly more potent as differentiation inducers.

  DOI：

  10.1021/jm070864w
• 作为产物：
  描述：

  O-三苯甲基羟胺 、 (E)-6-(1,3-二氢-4,6-二甲氧基-7-甲基-3-氧代-5-异苯并呋喃基)-4-甲基-4-己烯酸 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 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以43%的产率得到(E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methyl-N-trityloxyhex-4-enamide
  参考文献：
  名称：

  Dual Inhibitors of Inosine Monophosphate Dehydrogenase and Histone Deacetylases for Cancer Treatment

  摘要：

  Mycophenolic acid (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used worldwide in transplantation. Recently, numerous studies showed its importance in cancer treatment. Consequently, MPA entered clinical trials in advanced multiple myeloma patients. Suberoylanilide hydroxamic acid (SAHA), a potent differentiation agent acting through inhibition of histone deacetylases (HDACs), was recently approved for treatment of cutaneous T cell lymphoma. We report herein the synthesis of dual inhibitors of IMPDH and HDACs. We found that mycophenolic hydroxamic acid (9, MAHA) inhibits both IMPDH (K-i = 30 nM) and HDAC (IC50 = 5.0 mu M). A modification of SAHA with groups known to interact with IMPDH afforded a SAHA analogue 14, which inhibits IMPDH (K-i = 1.7 mu M) and HDAC (IC50 = 0.06 mu M). Both MAHA (IC50 = 4.8 mu M) and SAHA analogue 14 (IC50 = 7.7 mu M) were more potent than parent compounds as antiproliferation agents. They were also significantly more potent as differentiation inducers.

  DOI：

  10.1021/jm070864w