(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[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] | 1055988-70-9

• 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',3,6,6',19'-pentamethylspiro[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: 1055988-70-9
• 化学式: C₃₀H₄₅N₃O
• 分子量: 463.707
• InChiKey: HTAZVNGPBOCUMH-DNGXQMGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  34
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  、 甲基肼 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， 生成 (1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[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：

  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

• 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。
• 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.
• METHODS AND COMPOSITIONS FOR IDENTIFICATION, ASSESSMENT AND TREATMENT OF CANCERS ASSOCIATED WITH HEDGEHOG SIGNALING
  申请人：MacDougall John R.

  公开号：US20120010230A1

  公开（公告）日：2012-01-12

  Provided herein are methods, assays and kits for evaluating a sample, e.g., a sample obtained from a cancer patient, to detect one or more hedgehog biomarkers and/or one or more cilium markers. Thus, the invention can be used, inter alia, as a means to identify patients likely to benefit from administration of one or more hedgehog inhibitors, alone or in combination with therapeutic agents; to predict a time course of disease or a probability of a significant event in the disease of a cancer patient; to stratify patient populations; and/or to more effectively treat or prevent a cancer or a tumor associated with hedgehog signaling.