| 1612259-06-9

• CAS: 1612259-06-9
• 化学式: C₁₁H₂₅Cl₂N₃O₆Pt
• 分子量: 561.322
• InChiKey: RCVDZZKRZMVGLB-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  7-氨基-4-甲基香豆素 、 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以30%的产率得到
  参考文献：
  名称：

  Pt(IV) Prodrugs Designed to Bind Non-Covalently to Human Serum Albumin for Drug Delivery

  摘要：

  Albumin is the most abundant protein in human serum and drugs that are administered intravenously inevitably interact with it. We present here a series of platinum(IV) prodrugs designed specifically to enhance interaction with human serum albumin (HSA) for drug delivery. This goal is achieved by asymmetrically functionalizing the axial ligands of the prodrug so as to mimic the overall features of a fatty acid. Systematic variation of the length of the aliphatic tail tunes the cellular uptake and, consequently, the cytotoxicity of cis,cis,trans-[Pt(NH3)2Cl2(O2CCH2CH2COOH)(OCONHR)], 4, where R is a linear alkyl group. Investigation of an analogue bearing a fluorophore conjugated to the succinate ligand confirmed that these compounds are reduced by biological reductants with loss of the axial ligands. Intracellular release of cisplatin from 4 was further confirmed by observing the characteristic effects of cisplatin on the cell cycle and morphology following treatment with the prodrug. The most potent member of series 4, for which R is a hexadecyl chain, interacts with HSA in a 1:1 stoichiometry to form the platinum-protein complex 7. The interaction is non-covalent and extraction with octanol completely removes the prodrug from an aqueous solution of HSA. Construct 7 is robust and can be isolated following fast protein liquid chromatography. The nature of the tight interaction was investigated computationally, and these studies suggest that the prodrug is buried below the surface of the protein. Consequently, complexation to HSA is able to reduce the rate of reduction of the prodrug by ascorbate. The lead compound from series 4 also exhibited significant stability in whole human blood, attributed to its interaction with HSA. This favorable redox profile, in conjunction with the established nonimmunogenicity, biocompatibility, and enhanced tumor accumulation of HSA, produces a system that holds significant therapeutic potential.

  DOI：

  10.1021/ja5038269
• 作为产物：
  描述：

  异氰酸己酯 、 cis,cis-[Pt(IV)(NH3)2(Cl)2(OH)(O2CCH2CH2COOH)] 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  兼具亲疏水两性的铁蛋白顺铂前药及其制备方法和应用

  摘要：

  本发明公开了一种兼具亲疏水两性的铁蛋白顺铂前药及其制备方法和应用，涉及纳米生物学技术领域，本发明所述顺铂前药是在顺铂的中心铂原子轴向分别引入亲水和疏水轴配体而得，设计了一系列顺铂前药，来减少其在铁蛋白药物载体装载过程中的失活。我们通过温控通道装载法实现了铁蛋白‑顺铂前药的制备，并从结构上解释了铁蛋白‑顺铂前药复合物保持基于铂的药物活性的机制。在顺铂敏感和顺铂耐药的细胞系来源的肿瘤模型，以及病人组织来源的肿瘤模型中，我们均验证了铁蛋白‑顺铂前药在治疗肿瘤中的有效性和安全性。利用本发明所获得的顺铂前药和铁蛋白‑顺铂前药复合物可以实现高效的肿瘤治疗，并具有很高的临床转化前景。

  公开号：

  CN117720583A

文献信息

• 一类含有APR-246的四价铂配合物及其制备方法与应用
  申请人：中国人民解放军空军军医大学

  公开号：CN115746060A

  公开（公告）日：2023-03-07

  本发明公开了一种含有APR‑246的四价铂配合物，结构如通式I所示： 其中，n选自0、1、2、3、4；R选自 R1选自支链或直链的C1～C20烷基；R2选自支链或直链的C1～C20烷基。本发明提供的含有p53突变激活剂APR‑246的四价铂化合物，该类化合物可以提高APR‑246的抗肿瘤活性，并可以发挥APR‑246和二价铂类药物的抗肿瘤优势，利用APR‑246独特的抗肿瘤机制，与铂类药物一起发挥优异的协同抗肿瘤药效，同时对肿瘤的耐药性改善也有很大帮助。