benzyl (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-methoxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate | 1037210-60-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-methoxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate
• CAS: 1037210-60-8
• 化学式: C₃₇H₅₃NO₄
• 分子量: 575.832
• InChiKey: IZLOVSZSIAOBFD-UYRVZWPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  42
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-methoxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate 在 palladium 10% on activated carbon 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-methoxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]
  参考文献：
  名称：

  WO2008/83248

  摘要：

  公开号：
• 作为产物：
  描述：

  benzyl (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-hydroxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate 、 硫酸二甲酯 在 苄基三乙基氯化铵 、 potassium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 benzyl (3R,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3-methoxy-3',6',11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-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

文献信息

• Methods of use for cyclopamine analogs
  申请人：Infinity Discovery, Inc.

  公开号：EP2368551A2

  公开（公告）日：2011-09-28

  The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:

  本发明提供了使用具有下式的环丙胺衍生物治疗各种疾病的方法：
• Cyclopamine analogs
  申请人：Infinity Discovery, Inc.

  公开号：EP2443926A2

  公开（公告）日：2012-04-25

  The invention provides novel derivatives of cyclopamine having the following formula: wherein the nature of the moieties R1, R2, R3, R4, R7, R7', R8 and R9 is defined in appended claim 1.

  本发明提供了具有下式的环丙胺新型衍生物： 其中分子 R1、R2、R3、R4、R7、R7'、R8 和 R9 的性质在所附权利要求 1 中定义。
• WO2008/83248
  申请人：——

  公开号：——

  公开（公告）日：——
• CYCLOPAMINE ANALOGS
  申请人：Austad Brian

  公开号：US20080293754A1

  公开（公告）日：2008-11-27

  The invention provides novel derivatives of cyclopamine having the following formula:
• METHODS OF USE OF CYCLOPAMINE ANALOGS
  申请人：Castro Alfredo C.

  公开号：US20100286180A1

  公开（公告）日：2010-11-11

  The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula: