tert-butyl4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b] quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: tert-butyl4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b] quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate
• 英文别名: 4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b] quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate；tert-butyl 4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1 ,2-b]quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate
• 化学式: C₃₈H₄₅N₃O₁₁
• 分子量: 719.789
• InChiKey: IGYBGRZHVTZYQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.52
• 重原子数：
  52.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  161.79
• 氢给体数：
  0.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  tert-butyl4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b] quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate 、 4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-(ethoxycarbonyl)-4H-1,2,4-triazol-4-yl)phenoxy)benzoic acid 在 盐酸 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以54%的产率得到4,11-diethyl-9-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-4-yl(1-(4-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-(ethylcarbamoyl)-4H-1,2,4-triazol-4-yl)phenoxy)benzoyl)piperidin-4-yl) carbonate
  参考文献：
  名称：

  [EN] TARGETED THERAPEUTICS
  [FR] AGENTS THÉRAPEUTIQUES CIBLÉS

  摘要：

  公开号：

  WO2013158644A3
• 作为产物：
  描述：

  N-Boc-4-羟基哌啶 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 tert-butyl4-((((9-((tert-butoxycarbonyl)oxy)-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b] quinolin-4-yl)oxy)carbonyl)oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] TARGETED THERAPEUTICS
  [FR] AGENTS THÉRAPEUTIQUES CIBLES

  摘要：

  公开号：

  WO2015143004A9

文献信息

• [EN] TARGETED THERAPEUTICS<br/>[FR] THÉRAPEUTIQUE CIBLÉE
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2015038649A1

  公开（公告）日：2015-03-19

  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.

  本发明提供了包括与将效应子导向至感兴趣的生物靶点的结合基团共轭的药理化合物。同样，本发明提供了包括这些化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。这些化合物可以被描述为蛋白质相互作用结合基团-药物共轭（SDC-TRAP）化合物，其中包括蛋白质相互作用结合基团和效应子。例如，在针对治疗癌症的某些实施方式中，SDC-TRAP可以包括Hsp90抑制剂共轭到细胞毒性药剂作为效应子。
• TARGETED THERAPEUTICS
  申请人：Chimmanamada Dinesh U.

  公开号：US20140079636A1

  公开（公告）日：2014-03-20

  The present invention provides pharmacological compounds including an effector moiety conjugated to an 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.

  本发明提供了药理化合物，包括将效应器基团偶联到结合基团上，以将效应器基团定向到感兴趣的生物靶点。同样，本发明提供了包括该化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。该化合物可以被描述为蛋白质相互作用的结合基团-药物偶联物（SDC-TRAP）化合物，包括蛋白质相互作用的结合基团和效应器基团。例如，在治疗癌症的某些实施方案中，SDC-TRAP可以包括Hsp90抑制剂与细胞毒素剂作为效应器基团的偶联物。
• A BINDING MOIETY-DRUG CONJUGATE COMPRISING A HSP90 BINDING MOIETY AND A CYTOTOXIC EFFECTOR MOIETY
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：EP3466416A2

  公开（公告）日：2019-04-10

  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 HAVING AN HSP90 LIGAND AS BINDING MOIETY
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：EP3738594A1

  公开（公告）日：2020-11-18

  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 and therapeutic methods 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 which is an Hsp90 ligand and an effector moiety. The therapeutic uses include the treatment of cancer, chronic bronchitis, asthma, and actinic keratosis.

  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和治疗方法。这些化合物可以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，其中包括一个蛋白质相互作用结合分子（Hsp90 配体）和一个效应分子。治疗用途包括治疗癌症、慢性支气管炎、哮喘和日光性角化病。
• Targeted therapeutics
  申请人：MADRIGAL PHARMACEUTICALS, INC.

  公开号：US10675360B2

  公开（公告）日：2020-06-09

  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。