(1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-8-hydroxy-4a1,7,7,10a,12a-pentamethyl-3-oxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl acetate | 1072032-64-4

• 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
• 英文名称: (1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-8-hydroxy-4a1,7,7,10a,12a-pentamethyl-3-oxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl acetate
• 英文别名: [(1S,2R,4S,7S,8S,11R,12S,17R,19R)-7-(furan-3-yl)-15-hydroxy-1,8,12,16,16-pentamethyl-5-oxo-3,6-dioxapentacyclo[9.8.0.02,4.02,8.012,17]nonadec-13-en-19-yl] acetate
• CAS: 1072032-64-4
• 化学式: C₂₈H₃₆O₇
• 分子量: 484.59
• InChiKey: IYGKIJUHLXBVCF-DHVGKWQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  98.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-8-hydroxy-4a1,7,7,10a,12a-pentamethyl-3-oxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl acetate 、 乙酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以83%的产率得到(1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-4a1,7,7,10a,12a-pentamethyl-3-oxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromene-5,8-diyl diacetate
  参考文献：
  名称：

  Gedunin, a Novel Hsp90 Inhibitor: Semisynthesis of Derivatives and Preliminary Structure−Activity Relationships

  摘要：

  Gedunin (1), a tetranortriterpenoid isolated from the Indian neern tree (Azadirachta indica), was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors. The mechanism of action by which gedunin induces client protein degradation remains undetermined, however, prior studies have demonstrated that it does not bind competitively versus ATP. In an effort to further probe the mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells determined. Although no compound was found to exhibit antiproliferative activity more effective than the natural product, functionalities critical for antiproliferative activity have been identified.

  DOI：

  10.1021/jm8007486
• 作为产物：
  描述：

  葛杜宁 在 aluminum isopropoxide 、 异丙醇 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以56%的产率得到(1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-8-hydroxy-4a1,7,7,10a,12a-pentamethyl-3-oxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl acetate
  参考文献：
  名称：

  Gedunin, a Novel Hsp90 Inhibitor: Semisynthesis of Derivatives and Preliminary Structure−Activity Relationships

  摘要：

  Gedunin (1), a tetranortriterpenoid isolated from the Indian neern tree (Azadirachta indica), was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors. The mechanism of action by which gedunin induces client protein degradation remains undetermined, however, prior studies have demonstrated that it does not bind competitively versus ATP. In an effort to further probe the mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells determined. Although no compound was found to exhibit antiproliferative activity more effective than the natural product, functionalities critical for antiproliferative activity have been identified.

  DOI：

  10.1021/jm8007486

文献信息

• Targeted therapeutics
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：US10232049B2

  公开（公告）日：2019-03-19

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• TARGETED THERAPEUTICS
  申请人：Synta Pharmaceuticals Corp.

  公开号：US20170049899A1

  公开（公告）日：2017-02-23

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.