diaqua(1,2-diaminocyclohexane)platinum(II)

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: diaqua(1,2-diaminocyclohexane)platinum(II)
• 英文别名: (1R,2R)-cyclohexane-1,2-diamine;platinum(2+);dihydrate
• 化学式: C₆H₁₈N₂O₂Pt
• 分子量: 345.301
• InChiKey: FWZZTLRIXBYOKR-SKSSAGQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.44
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diaqua(1,2-diaminocyclohexane)platinum(II) 、 以 水 为溶剂， 生成
  参考文献：
  名称：

  [EN] MODIFIED PLATINUM COMPOUNDS AND THERAPEUTIC USES THEREOF
  [FR] COMPOSÉS DE PLATINE MODIFIÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  本公开涉及一般用于治疗癌症的化合物。在某些方面，本公开提供化学修饰的铂化合物，其具有一个或多个包括亲水性部分的基团。在某些方面，本公开提供包括这种修饰的铂化合物和蛋白质（例如白蛋白或白蛋白类似物）的组合物。此外，本公开提供了这些化合物和组合物的各种用途。

  公开号：

  WO2018175601A1
• 作为产物：
  描述：

  trans-1,2-Diaminocyclohexane 在 silver nitrate 作用下， 以 水 为溶剂， 反应 0.5h， 生成 diaqua(1,2-diaminocyclohexane)platinum(II)
  参考文献：
  名称：

  Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes

  摘要：

  Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl](2)(mu-pz)}(2+) (L, ethylenediamine, en; (+/-)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(+/-)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd) and one pyridazine (pydz) bridged {[Pt(en)Cl](2)(mu-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 mu M range. While {[Pt(1,3-pd)Cl](2)(mu-pz)}(2+) showed improved activity and {[Pt(en)Cl](2)(mu-pydz)}(2+) showed comparable activity to that of clinically relevant cisplatin, {[Pt(en)Cl](2)(mu-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics.

  DOI：

  10.1021/jm5017686

文献信息

• LIGAND-TARGETED MOLECULES AND METHODS THEREOF
  申请人：INVICTUS ONCOLOGY PVT.LTD.

  公开号：US20150045428A1

  公开（公告）日：2015-02-12

  The present invention relates to ligand-targeted molecules and ligand drug conjugates (LDCs) comprising a ligand connected to a functional group, which is connected to a linker, which in turn is bonded to a drug. The LDCs of the present invention also comprise platinum coordination complex wherein the platinum is connected to the linker through monocarboxylato and O→Pt coordinate bonds. The present invention also relates to methods for preparing these ligand drug conjugates. The present invention further relates to methods for the treatment of tumours using the ligand drug conjugates of the present invention.

  本发明涉及配体靶向分子和配体药物结合物（LDCs），其中配体连接到功能基团，功能基团连接到连接剂，连接剂又与药物结合。本发明的LDCs还包括铂配位络合物，其中铂通过单羧酸盐和O→Pt配位键与连接剂连接。本发明还涉及制备这些配体药物结合物的方法。本发明还涉及使用本发明的配体药物结合物治疗肿瘤的方法。
• Synthesis and biological evaluation of cholic acid-conjugated oxaliplatin as a new prodrug for liver cancer
  作者：Jing Jiang、Fuguo Han、Kaixuan Cai、Qiushuo Shen、Cuiping Yang、Anli Gao、Juan Yu、Xuemei Fan、Yanli Hao、Zhao Wang、Weiping Liu、Yun Shi、Qingfei Liu

  DOI：10.1016/j.jinorgbio.2023.112200

  日期：2023.6

  oxaliplatin, LLC-202, is developed as a novel prodrug for liver cancer. The conjugate is obtained by using 3-NH2−cyclobutane-1,1-dicarboxylate as a linker between the oxaliplatin analogue and cholic acid moiety and cholic acid is strongly bonded to the linker via an amide bond. Pharmacokinetic experiment shows that LLC-202 is mainly distributed and accumulated in the liver after intravenous administration to

  胆酸结合的奥沙利铂 LLC-202 是一种新型肝癌前药。通过使用 3-NH 2 -获得缀合物1,1-环丁烷二羧酸酯作为奥沙利铂类似物和胆酸部分之间的连接体，胆酸通过酰胺键与连接体牢固结合。药代动力学实验表明，给Sprague-Dawley大鼠静脉注射后，LLC-202主要在肝脏中分布和积累，揭示了肝脏靶向特性。与奥沙利铂相比，LLC-202比正常人肝细胞更容易被人肝癌细胞摄取。LLC-202 在治疗 C57BL/6 小鼠原发性肝细胞癌方面表现出比奥沙利铂更高的体外抗癌活性和更高的疗效。通过诱导癌细胞凋亡、抑制癌细胞增殖，可显着延长荷瘤小鼠的生存时间。此外，LLC-202 对正常人肝细胞的细胞毒性低于奥沙利铂。其对健康昆明（KM）小鼠静脉注射后的急性毒性与奥沙利铂相当。组织病理学检查表明LLC-202对小鼠的主要毒性是抑制骨髓造血细胞。结果表明，LLC-202作为一种针对肝癌的新型前药具有进一步开发的巨大潜力。
• 偶联吲哚菁绿和奥沙利铂的白蛋白纳米粒及其制备与应用
  申请人：苏州大学

  公开号：CN114732900A

  公开（公告）日：2022-07-12

  本发明公开了偶联吲哚菁绿和奥沙利铂的白蛋白纳米粒及其制备与应用，采用新工艺并由生物矿化方法，成功制得共偶联吲哚菁绿、奥沙利铂白蛋白纳米粒（OXP‑ICG NPs）。本发明纳米粒的制备条件温和，简单易行。经过制剂学相关表征，纳米粒符合被动靶向给药系统要求。细胞试验中，MTT试验，化疗‑光疗结合的纳米粒OXP‑ICG NPs，对CT26结肠癌细胞，具有显著的：1）抑瘤作用（IC50由12.23~28.56降为4.77）；2）抗肿瘤协同作用（协同指数0.56）；可增加1.45倍肿瘤细胞对OXP的吞噬量，并增加94.33%的细胞凋亡；从而证实了OXP‑ICG NPs高效抑制肿瘤细胞生长，具有化疗‑光疗的协同治疗效果；并且新制备工艺提升了中间体制备水平。
• Synthesis and Evaluation of Series of Diazine-Bridged Dinuclear Platinum(II) Complexes through in Vitro Toxicity and Molecular Modeling: Correlation between Structure and Activity of Pt(II) Complexes
  作者：Lidija Senerovic、Marija D. Zivkovic、Aleksandar Veselinovic、Aleksandar Pavic、Milos I. Djuran、Snezana Rajkovic、Jasmina Nikodinovic-Runic

  DOI：10.1021/jm5017686

  日期：2015.2.12

  Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas [Pt(L)Cl](2)(mu-pz)}(2+) (L, ethylenediamine, en; (+/-)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(+/-)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd) and one pyridazine (pydz) bridged [Pt(en)Cl](2)(mu-pydz)}(2+) complex were prepared. The anticancer potential of these complexes were determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and HCT116), interaction with double stranded DNA through in vitro assay, and molecular docking study. All complexes inhibited cell proliferation with inhibitory concentrations in the 0.5-120 mu M range. While [Pt(1,3-pd)Cl](2)(mu-pz)}(2+) showed improved activity and [Pt(en)Cl](2)(mu-pydz)}(2+) showed comparable activity to that of clinically relevant cisplatin, [Pt(en)Cl](2)(mu-pydz)}(2+) was less toxic in an assay with zebrafish (Danio rerio) embryos, causing no adverse developmental effects. The in vitro cytotoxicity of all diazine-bridged dinuclear Pt(II) complexes is discussed in correlation to their structural characteristics.
• [EN] MODIFIED PLATINUM COMPOUNDS AND THERAPEUTIC USES THEREOF<br/>[FR] COMPOSÉS DE PLATINE MODIFIÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：UNIV CALIFORNIA

  公开号：WO2018175601A1

  公开（公告）日：2018-09-27

  The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides platinum compounds that are chemically modified to have one or more moieties that include hydrophobic portions. In some aspects, the disclosure provides compositions that include such modified platinum compounds and a protein, such as albumin or albumin mimetics. Further, the disclosure provides various uses of these compounds and compositions.

  本公开涉及一般用于治疗癌症的化合物。在某些方面，本公开提供化学修饰的铂化合物，其具有一个或多个包括亲水性部分的基团。在某些方面，本公开提供包括这种修饰的铂化合物和蛋白质（例如白蛋白或白蛋白类似物）的组合物。此外，本公开提供了这些化合物和组合物的各种用途。