(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6-oxa-5,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene] | 1170689-25-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6-oxa-5,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene]
• CAS: 1170689-25-4
• 化学式: C₂₈H₄₁N₃O₂
• 分子量: 451.652
• InChiKey: XRWWFUCKKOEAQY-ZIWZFDMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 2.0h， 以11 mg的产率得到(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6-oxa-5,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene]
  参考文献：
  名称：

  Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)

  摘要：

  Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or Solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.

  DOI：

  10.1021/jm900305z