(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethyl-6'-methylsulfonylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene] | 1055988-72-1

• 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'-tetramethyl-6'-methylsulfonylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene]
• CAS: 1055988-72-1
• 化学式: C₃₀H₄₅N₃O₃S
• 分子量: 527.772
• InChiKey: AFNXIPKHZVONCA-DNGXQMGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  环巴胺 在 palladium(II) hydroxide/carbon 、 palladium 10% on activated carbon 吡啶 、 4-二甲氨基吡啶 、 二(2,6-二甲基苯基)磷酸氢酯 、 potassium tert-butylate 、 氢气 、 diethylzinc 、 aluminum tri-tert-butoxide 、 三乙胺 、 丁酮 、 肼 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， -20.0~75.0 ℃ 、101.33 kPa 条件下， 反应 79.75h， 生成 (1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,19'-tetramethyl-6'-methylsulfonylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-6,7-diazapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4,7,19-triene]
  参考文献：
  名称：

  WO2008/109184

  摘要：

  公开号：

文献信息

• HETEROCYCLIC CYCLOPAMINE ANALOGS AND METHODS OF USE THEREOF
  申请人：Castro Alfredo C.

  公开号：US20080293755A1

  公开（公告）日：2008-11-27

  The present invention relates to steroidal alkaloids that can be used in the treatment of hedgehog pathway related disorders, particularly cancer.

  本发明涉及可用于治疗刺猬通路相关疾病，特别是癌症的类固醇生物碱。
• Heterocyclic Cyclopamine Analogs and Methods of Use Thereof
  申请人：Castro Alfredo C.

  公开号：US20120065218A1

  公开（公告）日：2012-03-15

  The present invention relates to steroidal alkaloids that can be used in the treatment of hedgehog pathway related disorders, particularly cancer.

  本发明涉及类固醇生物碱，可用于治疗刺猬通路相关疾病，特别是癌症。
• Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)
  作者：Martin R. Tremblay、André Lescarbeau、Michael J. Grogan、Eddy Tan、Grace Lin、Brian C. Austad、Lin-Chen Yu、Mark L. Behnke、Somarajan J. Nair、Margit Hagel、Kerry White、James Conley、Joseph D. Manna、Teresa M. Alvarez-Diez、Jennifer Hoyt、Caroline N. Woodward、Jens R. Sydor、Melissa Pink、John MacDougall、Matthew J. Campbell、Jill Cushing、Jeanne Ferguson、Michael S. Curtis、Karen McGovern、Margaret A. Read、Vito J. Palombella、Julian Adams、Alfredo C. Castro

  DOI：10.1021/jm900305z

  日期：2009.7.23

  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.
• TREATMENT OF FIBROTIC CONDITIONS USING HEDGEHOG INHIBITORS
  申请人：Levine Arnold J.

  公开号：US20110183948A1

  公开（公告）日：2011-07-28

  Provided is a method of treating a fibrotic condition with a hedgehog inhibitor.
• THERAPEUTIC REGIMENS FOR HEDGEHOG-ASSOCIATED CANCERS
  申请人：MacDougall John R.

  公开号：US20120010229A1

  公开（公告）日：2012-01-12

  Provided herein are methods, therapeutic regimens, and kits that optimize the benefits of hedgehog inhibition for cancer therapy.