(Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenyl (4-nitrophenyl)carbonate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenyl (4-nitrophenyl)carbonate
• 英文别名: [2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] (4-nitrophenyl) carbonate
• 化学式: C₂₅H₂₃NO₉
• 分子量: 481.459
• InChiKey: LEILCPKQXQOZMO-WAYWQWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenyl (4-nitrophenyl)carbonate 在 吡啶 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Combretastatin A4-derived payloads for antibody-drug conjugates

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113355
• 作为产物：
  描述：

  (Z)-3,4,5,4',-四甲氧基-3'-羟基二苯乙烯 、 氯甲酸对硝基苄酯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以75%的产率得到(Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenyl (4-nitrophenyl)carbonate
  参考文献：
  名称：

  康维他汀A-4的NQO1选择性活化前药：合成和生物学评估。

  摘要：

  特定于肿瘤的前药治疗使抗肿瘤药的排他性传递降到最低。在这项工作中，我们报告了由活性药物CA-4，不同的自消灭性接头和NQO1反应性触发基团构成的四种NQO1可激活的康维他汀A-4前药的合成和生物学评估。体外抗增殖活性表明，前药4对过表达NQO1，紫杉醇抗性A549细胞，低氧暴露的A549和HepG2细胞的肿瘤细胞具有更大的选择性毒性，与康布雷他汀A-4相比，对正常细胞的损伤较小，前药1，2，和3。此外，基于机理研究，NQO1触发了前药4有效释放母体药物康普他汀A-4并杀死肿瘤细胞。此外，我们还证明，在体内条件下，前药4的抗癌作用和安全性均高于康培他汀A-4。因此，根据以上结果，NQO1可以用作释放抗癌剂的特定递送系统。此外，前药4可以作为开发特定抗癌药的候选药物。

  DOI：

  10.1016/j.bioorg.2020.104200

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。
• 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。
• New somatostatin-drug conjugates for effective targeting pancreatic cancer
  作者：E. Ragozin、A. Hesin、A. Bazylevich、H. Tuchinsky、A. Bovina、T. Shekhter Zahavi、M. Oron-Herman、G. Kostenich、M.A. Firer、T. Rubinek、I. Wolf、G. Luboshits、M.Y. Sherman、G. Gellerman

  DOI：10.1016/j.bmc.2018.06.032

  日期：2018.7

  Pancreatic cancer poorly responds to available drugs, and finding novel approaches to target this cancer type is of high significance. Here, based on a common property of pancreatic cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5. Three major drugs were conjugated to our best SSTps that served as delivery vehicles, including Camptothecin (CPT), Combretastatin-4A (COMB) and Azatoxin (AZA). All designed drug conjugates demonstrated penetration to pancreatic cancer cell lines, and significant toxicity towards them. Furthermore, the drug conjugates specifically accumulated in tumors in the animal xenograft model, though some accumulation was also seen in kidney. Overall these findings lay the basis for development of novel drug series that could target the fatal pancreatic cancer.
• [EN] TARGETED THERAPEUTICS<br/>[FR] AGENTS THÉRAPEUTIQUES CIBLÉS
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2013158644A3

  公开（公告）日：2014-01-30