| 1170689-26-5

• 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
• CAS: 1170689-26-5
• 化学式: C₃₈H₄₈F₃NO₅
• 分子量: 655.798
• InChiKey: BFZJVDJVWANVJH-HQCHSXPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.71
• 重原子数：
  47.0
• 可旋转键数：
  2.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  76.07
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 benzyl (1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethyl-5'-(trifluoromethyl)spiro[3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine-2,17'-6,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4(8),5,19-triene]-4-carboxylate
  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
• 作为产物：
  描述：

  三氟乙酸乙酯 、 benzyl (3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3',6',11,12b-tetramethyl-3-oxospiro[2,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydro-1H-naphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate 在 potassium tert-butylate 、 水 、 sodium hydroxide 作用下， 以 叔丁醇 为溶剂， 以94%的产率得到
  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