cis-dichloro-(trans-1R,2R-cyclohexanediamine)platinum(II)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 金属杂环化合物
• 英文名称: cis-dichloro-(trans-1R,2R-cyclohexanediamine)platinum(II)
• 英文别名: Pt(dach)Cl₂；[PtCl2(cis-1,4-DACH)]；Pt(R,R-DACH)Cl2；Pt(trans-l-1,2-diaminocyclohexane)Cl2；[(1R,2R)-2-azanidylcyclohexyl]azanide;platinum(4+);dichloride
• 化学式: C₆H₁₂Cl₂N₂Pt
• 分子量: 378.161
• InChiKey: UUERTZXRKZEANK-SKSSAGQDSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 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：
  2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cis-dichloro-(trans-1R,2R-cyclohexanediamine)platinum(II) 、 cesium oxalate 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以25%的产率得到oxaliplatin
  参考文献：
  名称：

  [EN] PREPARATION OF PLATINUM(II) COMPLEXES
  [FR] PREPARATION DE COMPLEXES DE PLATINE (II)

  摘要：

  这项发明涉及一种制备含有中性双齿配体的铂（II）配合物的方法，例如奥沙利铂。该方法包括将含有中性双齿配体的卤代铂配合物与草酸盐在溶剂中反应的步骤，其中溶剂中草酸盐的溶解度超过1 g/L。该发明还涉及新的铂（II）配合物。

  公开号：

  WO2006024897A1
• 作为产物：
  描述：

  [PtI2(1(R),2(R)-DACH)] 在 silver nitrate 、 potassium chloride 作用下， 以 水 为溶剂， 反应 30.5h， 以94%的产率得到cis-dichloro-(trans-1R,2R-cyclohexanediamine)platinum(II)
  参考文献：
  名称：

  Revisiting [PtCl₂(cis-1,4-DACH)]: An Underestimated Antitumor Drug with Potential Application to the Treatment of Oxaliplatin-Refractory Colorectal Cancer

  摘要：

  Although the encouraging antitumor activity of [PtCl2(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing the isomeric 1(R),2(R)DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemotherapy-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with double-stranded DNA, investigated by a biosensor assay and by quantum mechanical/molecular mechanical geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.

  DOI：

  10.1021/jm3006838

文献信息

• Platinum(II) Complexes of Curcumin Showing Photocytotoxicity in Visible Light
  作者：Koushambi Mitra、Srishti Gautam、Paturu Kondaiah、Akhil R. Chakravarty

  DOI：10.1002/ejic.201601078

  日期：2017.3.27

  of photoactive curcumin. The crystal structure of Pt(NH3)(2)(acac)] CF3SO3 (4a) revealed square-planar geometry of the platinum(II) centre. Complexes 1-3 displayed an intense absorption band at 450 nm (epsilon = 22500 M-1 cm-1). The curcumin in metal-bound form showed improved stability in 10 % DMSO/buffer solution at 37 degrees C. The complexes released curcumin upon irradiation with visible light

  姜黄素的三种铂 (II) 络合物 Pt(NH3)(2)( cur)](NO3) (1)、Pt(en)(cur)](NO3) (2) 和 Pt(dach)(cur)] (NO3) (3)，其中 Hcu 是姜黄素，en 是乙二胺，dach 是 1R,2R-(-)-1,2-二氨基环己烷，被合成、表征并探索了它们的光细胞毒性。制备 1 的乙酰丙酮 (Hacac) 类似物 Pt(NH3)(2)(acac)] NO3 (4)，以研究光活性姜黄素的作用。Pt(NH3)(2)(acac)] CF3SO3 (4a) 的晶体结构揭示了铂(II) 中心的方形平面几何形状。复合物 1-3 在 450 nm (epsilon = 22500 M-1 cm-1) 处显示出强烈的吸收带。金属结合形式的姜黄素在 37 摄氏度的 10% DMSO/缓冲溶液中表现出更高的稳定性。从发射强度的增加可以看出，在可见光 (400-700
• [EN] EPSILON-POLY-L-LYSINE-BASED DRUG CONJUGATE, INTERMEDIATE THEREOF, AND APPLICATION THEREOF<br/>[FR] CONJUGUÉ DE MÉDICAMENT À BASE D'EPSILON-POLY-L-LYSINE, INTERMÉDIAIRE DE CELUI-CI, ET SON APPLICATION<br/>[ZH] 一种基于ε-聚-L-赖氨酸的药物偶联物、其中间体及其应用
  申请人：[en]SHANGHAI BEST-LINK BIOSCIENCE, LLC;[zh]上海弼领生物技术有限公司

  公开号：WO2023078464A1

  公开（公告）日：2023-05-11

  本发明公开了一种基于ε-聚-L-赖氨酸的药物偶联物、其中间体及其应用。本发明提供了一种如式(I)所示的具有基团偶联数量可控和基团偶联位点可控的ε-聚-L-赖氨酸衍生物-药物偶联物。本发明的药物偶联物具有肾脏清除率低、肝脾清除率低、血浆半衰期长、快速在病灶蓄积有效药物浓度和治疗效果更好的效果优势中的一个或多个。
• Phosphaplatins, next generation platinum antitumor agents: A paradigm shift in designing and defining molecular targets
  作者：Shadi Moghaddas、Pooja Majmudar、Roberto Marin、Homa Dezvareh、Chunyan Qi、Eroica Soans、Rathindra N. Bose

  DOI：10.1016/j.ica.2012.05.040

  日期：2012.12

  Platinum(II)- and platinum(IV)-pyrophosphato-complexes (phosphaplatins) show excellent antitumor properties against a variety of human ovarian cancers, including cisplatin-and carboplatin-sensitive and resistant human cancers. To identify the lead compound of this class of non-DNA binding antitumor agents, stereoisomers of cis- and trans-1,2-cyclohexane-diamine(pyrophosphato) platinum(II) and of cis- and trans-1,2-cyclohexane-trans-dihydroxo-diamine(pyrophosphato) platinum(IV) were synthesized, and their in vitro efficacies were evaluated in a variety of human ovarian cancer cells including cisplatin-and carboplatin-resistant cancer cells. Some of these compounds exhibited IC50 values as low as 0.40 lM, the lowest ever observed for any platinum anticancer drugs under identical conditions. More importantly, these compounds are highly active against cisplatin-and carboplatin-sensitive and resistant cancers; examples of these cancer cells include cisplatin-sensitive A2780, acquired cisplatin-and carboplatin-resistant A2780/C30, and inherent cisplatin-resistant OVCAR-10 cells. In vivo efficacy determined by using human ovarian xenografts indeed confirmed that phosphaplatins are quite effective in treating ovarian cancers. The superiority of phosphaplatins was observed in increased life span and tumor regression. These non-DNA binding compounds exhibit cytotoxicity in ovarian cancers primarily through apoptosis via cell cycle arrest both at S and G2 phases largely in a dose independent manner. Platinum(II) compounds showed reduced protein binding compared to either cisplatin or carboplatin. Furthermore, protein binding by phosphaplatins was largely limited to extracellular and cytosolic compartments. In vivo experiments revealed that platinum accumulations in kidney of mice were significantly less compared to cisplatin. The maximum tolerated dose was found be >60 mg/kg via intravenous administration. Furthermore, rats treated with R, R-stereomer of the platinum(II) complex exhibited near normal white blood cell, platelet, and neutrophil counts indicating its non-toxic properties. Furthermore, the lead compound also stays in plasma for 24 h giving ample time to reach desired targets. Taken together, these data indicate that phosphaplatins have the potential to treat resistant ovarian cancers, both acquired and de novo, without exhibiting severe toxic effects. (C) 2012 Elsevier B. V. All rights reserved.
• [EN] PREPARATION OF PLATINUM(II) COMPLEXES<br/>[FR] PREPARATION DE COMPLEXES DE PLATINE (II)
  申请人：PLATCO TECHNOLOGIES PROPRIETAR

  公开号：WO2006024897A1

  公开（公告）日：2006-03-09

  This invention relates to a method for the preparation of a platinum(II) complex containing a neutral bidentate ligand, such as oxaliplatin. The method includes the step of reacting a halogenoplatinum complex containing a neutral bidentate ligand with an oxalate salt in a solvent, wherein more than 1 g/L of the oxalate salt is soluble in the solvent. The invention also relates to new platinum(II) complexes.

  这项发明涉及一种制备含有中性双齿配体的铂（II）配合物的方法，例如奥沙利铂。该方法包括将含有中性双齿配体的卤代铂配合物与草酸盐在溶剂中反应的步骤，其中溶剂中草酸盐的溶解度超过1 g/L。该发明还涉及新的铂（II）配合物。
• Revisiting [PtCl₂(<i>cis</i>-1,4-DACH)]: An Underestimated Antitumor Drug with Potential Application to the Treatment of Oxaliplatin-Refractory Colorectal Cancer
  作者：Nicola Margiotta、Cristina Marzano、Valentina Gandin、Domenico Osella、Mauro Ravera、Elisabetta Gabano、James A. Platts、Emanuele Petruzzella、James D. Hoeschele、Giovanni Natile

  DOI：10.1021/jm3006838

  日期：2012.8.23

  Although the encouraging antitumor activity of [PtCl2(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing the isomeric 1(R),2(R)DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemotherapy-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with double-stranded DNA, investigated by a biosensor assay and by quantum mechanical/molecular mechanical geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.