(1'S,2S,2'R,3R,3aS,6S,7aR,8'S,11'R,12'S)-2',3,6,6',17'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,15'-6-azatetracyclo[9.8.0.02,8.012,18]nonadec-17-ene]-5'-one | 1055981-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (1'S,2S,2'R,3R,3aS,6S,7aR,8'S,11'R,12'S)-2',3,6,6',17'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,15'-6-azatetracyclo[9.8.0.02,8.012,18]nonadec-17-ene]-5'-one
• CAS: 1055981-26-4
• 化学式: C₂₉H₄₆N₂O₂
• 分子量: 454.696
• InChiKey: JFFUSPZCOOUGNG-HUUCRYTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1'S,2S,2'R,3R,3aS,6S,7aR,8'S,11'R,12'S)-2',3,6,6',17'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,15'-6-azatetracyclo[9.8.0.02,8.012,18]nonadec-17-ene]-5'-one 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (1'S,2S,2'R,3R,3aS,6S,7aR,8'S,11'R,12'S)-2',3,6,6',17'-pentamethyl-4-methylsulfonylspiro[3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine-2,15'-6-azatetracyclo[9.8.0.02,8.012,18]nonadec-17-ene]-5'-one
  参考文献：
  名称：

  WO2008/109829

  摘要：

  公开号：
• 作为产物：
  描述：

  环巴胺 在 Wilkinson's catalyst 、 palladium hydroxide on carbon 、 palladium 10% on activated carbon 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 二(2,6-二甲基苯基)磷酸氢酯 、 盐酸羟胺 、 potassium tert-butylate 、 氢气 、 diethylzinc 、 sodium acetate 、 双(三甲基硅烷基)氨基钾 、 aluminum tri-tert-butoxide 、 三乙胺 、 丁酮 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， -78.0~80.0 ℃ 、101.33 kPa 条件下， 反应 101.25h， 生成 (1'S,2S,2'R,3R,3aS,6S,7aR,8'S,11'R,12'S)-2',3,6,6',17'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,15'-6-azatetracyclo[9.8.0.02,8.012,18]nonadec-17-ene]-5'-one
  参考文献：
  名称：

  WO2008/109829

  摘要：

  公开号：

文献信息

• 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.
• CYCLOPAMINE LACTAM ANALOGS AND METHODS OF USE THEREOF
  申请人：Infinity Discovery, Inc.

  公开号：EP2134719B1

  公开（公告）日：2013-07-17
• 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.