(1R, 2R-cylohexanediamine) dihydrogen-pyrophosphato-platinum(II) | 1339960-28-9

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 英文名称: (1R, 2R-cylohexanediamine) dihydrogen-pyrophosphato-platinum(II)
• 英文别名: (R,R)-cyclohexanediamine(pyrophosphato)platinum (II)；R,R-trans-1,2-cyclohexane-diamine (dihydrogenpyrophosphato)platinum(II)；(1R,2R)-(diaminocyclohexane)(dihydropyrophosphato)platinum(II)；(R,R)-DACH-2；Pt(dihydrogenpyrophosphato)(1R,2R‐diaminocyclohexane)；Pt(dihydrogenpyrophosphato)(1R,2R‐DACH)；Cyclohexanediamine pyrophosphatoplatinum(II), (1R,2R)-；(1R,2R)-cyclohexane-1,2-diamine;[hydroxy(oxido)phosphoryl] hydrogen phosphate;platinum(2+)
• CAS: 1339960-28-9
• 化学式: C₆H₁₆N₂O₇P₂Pt
• 分子量: 485.23
• InChiKey: SCMHTXQHAHWVSX-BNTLRKBRSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -1.86
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  9

制备方法与用途

亚胺福铂是一种铂基制剂，属于磷铂家族，具有抗肿瘤活性。

反应信息

• 作为产物：
  描述：

  tetrasodium pyrophosphate decahydrate 、 [SP-4-2-(1R-反式)]-(1,2-环己烷二胺-N,N')二氯化物铂(II) 在 硝酸 作用下， 以 甲醇 、 水 为溶剂， 反应 26.0h， 以89.7%的产率得到(1R, 2R-cylohexanediamine) dihydrogen-pyrophosphato-platinum(II)
  参考文献：
  名称：

  [EN] SYNTHETIC AND PURIFICATION METHODS FOR PHOSPHAPLATIN COMPOUNDS AND USES THEREOF
  [FR] PROCÉDÉS DE SYNTHÈSE ET DE PURIFICATION DE COMPOSÉS DE PHOSPHAPLATINE ET LEURS UTILISATIONS

  摘要：

  本申请公开了制备和纯化磷铂化合物的新方法和过程。合成方法和纯化过程的改进包括但不限于，高效、可重复的大规模制备这些有用的药物制剂，以高质量和良好的产率为特点。

  公开号：

  WO2013176764A1

文献信息

• New Oxaliplatin-Pyrophosphato Analogs with Improved In Vitro Cytotoxicity
  作者：Alessandra Barbanente、Rosa Maria Iacobazzi、Amalia Azzariti、James D. Hoeschele、Nunzio Denora、Paride Papadia、Concetta Pacifico、Giovanni Natile、Nicola Margiotta

  DOI：10.3390/molecules26113417

  日期：——

  Two new Pt(II)-pyrophosphato complexes containing the carrier ligands cis-1,3-diaminocyclohexane (cis-1,3-DACH) and trans-1,2-diamine-4-cyclohexene (1,2-DACHEX), variants of the 1R,2R-diaminocyclohexane ligand present in the clinically used Pt-drug oxaliplatin, have been synthesized with the aim of developing new potential antitumor drugs with high bone tropism. The complexes are more stable at physiological

  两种新型 Pt(II)-焦磷酸络合物，含有载体配体顺式-1,3-二氨基环己烷 ( cis -1,3-DACH) 和反式-1,2-二胺-4-环己烯 (1,2-DACHEX) 变体临床使用的Pt药物奥沙利铂中存在的1R , 2R-二氨基环己烷配体的合成，旨在开发具有高骨向性的新型潜在抗肿瘤药物。该配合物在生理 pH 条件下比在酸性条件下更稳定，其中 Na 2 [Pt(焦磷酸)( cis -1,3-DACH)] ( 1 ) 比 [Pt(二氢焦磷酸)(1,2-DACHEX) 稍稳定]（ 2 ）。在酸性 pH 值下更高的反应性确保了在肿瘤部位的更大功效。初步 NMR 研究表明1和2与 5'-GMP（用作核酸模型）缓慢反应，释放焦磷酸配体并提供双 5'-GMP 加合物。针对四种人类癌细胞系进行的体外细胞毒性测定表明，这两种化合物比奥沙利铂更具活性。对HCT116细胞的流式细胞术研究表明，具有非经典1,3-和1
• 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] SYNTHETIC AND PURIFICATION METHODS FOR PHOSPHAPLATIN COMPOUNDS AND USES THEREOF<br/>[FR] PROCÉDÉS DE SYNTHÈSE ET DE PURIFICATION DE COMPOSÉS DE PHOSPHAPLATINE ET LEURS UTILISATIONS
  申请人：PHOSPLATIN THERAPEUTICS LLC

  公开号：WO2013176764A1

  公开（公告）日：2013-11-28

  This application discloses novel methods and processes for preparation and purification of phosphaplatin compounds. The improvements of the synthetic methods and purification processes include, but are not limited to, efficient and reproducible large-scale preparation of these useful pharmaceutical agents in high quality and good yield.

  本申请公开了制备和纯化磷铂化合物的新方法和过程。合成方法和纯化过程的改进包括但不限于，高效、可重复的大规模制备这些有用的药物制剂，以高质量和良好的产率为特点。