[Pt(ethylenediamine)(dimethylformamide)Cl](NO₃) | 247596-18-5

• 英文名称: [Pt(ethylenediamine)(dimethylformamide)Cl](NO₃)
• 英文别名: [Pt(ethylenediamine)(dmf)Cl]NO₃；[Pt(ethylenediamine)Cl(DMF)]NO₃；[Pt(en)(dmf)Cl](NO₃)；[Pt(en)Cl(DMF)]NO₃
• CAS: 247596-18-5
• 化学式: C₅H₁₅ClN₃OPt*NO₃
• 分子量: 425.731
• InChiKey: MMNSYQUHBMVLEZ-UHFFFAOYSA-M

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：

  [Pt(ethylenediamine)(dimethylformamide)Cl](NO₃) 、 苯胺 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 生成 [Pt(II)aniline(ethylenediamine)Cl](NO3)
  参考文献：
  名称：

  Relative rates of reaction of Pt(en)Cl (NH2R)+ with guanosine monophosphate as a function of amino group substituent: Toward efficient labeling of DNA for TEM imaging

  摘要：

  In an attempt to understand the factors that govern the rates of reaction of the complexes [Pt(en) Cl(NH2R)]+NO3- (en = ethylene diamine) with guanosine monophosphate (dGMP) a series of amine complexes, where R=C8H9NO2 (benzo[d][1,3]dioxol-5-ylmethanamine) (1), C8H11N (phenethylamine) (2), C7H9N (benzylamine) (3), C6H7N (aniline) (4), C6H6IN (p-iodo-aniline) (5) C3H9NO (2-methoxyethylamine) (6) and C6H13N (cyclohexylamine) (7), were synthesized and their reactions with deoxyguanosine monophosphate (dGMP) were followed by H-1 NMR. Compound 1 was initially chosen because it showed significant water solubility. Compound 1 reacted quantitatively but slowly with dGMP and a subsequent Transmission Electron Microscopy (TEM) study of the binding 1 to a GATC DNA repeat gave a TEM micrograph that showed selective labeling of DNA at guanine, using a technique that allowed the laying down of a straight single strand of DNA on a carbon platform. The TEM suggested a possible side reaction with adenine and so a study of the reaction of 1 with adenine was performed and showed slow and what appeared to be non-specific binding to deoxyadenosine monophosphate (dAMP). The reactions of compounds 2-7 with dGMP were then studied by H-1 NMR and it was found that 2 reacted much faster than 1 with dGMP while the remaining complexes reacted more slowly. No reaction of 2 with dAMP was observed in the same time frame. The ultimate goal of the project was to bind a third row transition metal cluster to guanine and given the effective binding of 1 to DNA the synthesis of the complex [Os-3(CO)(11)PPh2(CH2)(2)NH2(en)PtCl]NO3 (9) is also reported that contains Pt as a linker to label guanine. The synthesis was performed by reacting Os-3(CO)(10)(CH3CN)(2) with Ph2PCH2CH2NH2 which gave an eta(2) chelate complex Os-3(CO)(10)PPh2(CH2)(2)NH2 (8). Complex 8 was reacted with [Pt(en)Cl(DMF)]NO3 in a CO atmosphere to give 9. H-1 and Pt-195 NMR indicate formation of an adduct with dGMP but too slowly to be of use in labeling DNA. The solid-state structure of 8 is also reported. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2012.11.003
• 作为产物：
  描述：

  乙二胺氯化铂(II) 、 N,N-二甲基甲酰胺 在 silver nitrate 作用下， 反应 16.0h， 生成 [Pt(ethylenediamine)(dimethylformamide)Cl](NO₃)
  参考文献：
  名称：

  Relative rates of reaction of Pt(en)Cl (NH2R)+ with guanosine monophosphate as a function of amino group substituent: Toward efficient labeling of DNA for TEM imaging

  摘要：

  In an attempt to understand the factors that govern the rates of reaction of the complexes [Pt(en) Cl(NH2R)]+NO3- (en = ethylene diamine) with guanosine monophosphate (dGMP) a series of amine complexes, where R=C8H9NO2 (benzo[d][1,3]dioxol-5-ylmethanamine) (1), C8H11N (phenethylamine) (2), C7H9N (benzylamine) (3), C6H7N (aniline) (4), C6H6IN (p-iodo-aniline) (5) C3H9NO (2-methoxyethylamine) (6) and C6H13N (cyclohexylamine) (7), were synthesized and their reactions with deoxyguanosine monophosphate (dGMP) were followed by H-1 NMR. Compound 1 was initially chosen because it showed significant water solubility. Compound 1 reacted quantitatively but slowly with dGMP and a subsequent Transmission Electron Microscopy (TEM) study of the binding 1 to a GATC DNA repeat gave a TEM micrograph that showed selective labeling of DNA at guanine, using a technique that allowed the laying down of a straight single strand of DNA on a carbon platform. The TEM suggested a possible side reaction with adenine and so a study of the reaction of 1 with adenine was performed and showed slow and what appeared to be non-specific binding to deoxyadenosine monophosphate (dAMP). The reactions of compounds 2-7 with dGMP were then studied by H-1 NMR and it was found that 2 reacted much faster than 1 with dGMP while the remaining complexes reacted more slowly. No reaction of 2 with dAMP was observed in the same time frame. The ultimate goal of the project was to bind a third row transition metal cluster to guanine and given the effective binding of 1 to DNA the synthesis of the complex [Os-3(CO)(11)PPh2(CH2)(2)NH2(en)PtCl]NO3 (9) is also reported that contains Pt as a linker to label guanine. The synthesis was performed by reacting Os-3(CO)(10)(CH3CN)(2) with Ph2PCH2CH2NH2 which gave an eta(2) chelate complex Os-3(CO)(10)PPh2(CH2)(2)NH2 (8). Complex 8 was reacted with [Pt(en)Cl(DMF)]NO3 in a CO atmosphere to give 9. H-1 and Pt-195 NMR indicate formation of an adduct with dGMP but too slowly to be of use in labeling DNA. The solid-state structure of 8 is also reported. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2012.11.003

文献信息

• [EN] CLEAVABLE CONJUGATES OF FUNCTIONALIZED PLATINUM-ACRIDINE AND PLATINUM-BENZACRIDINE AGENTS AND METHODS THEREOF<br/>[FR] CONJUGUÉS CLIVABLE D'AGENTS DE PLATINE-ACRIDINE ET DE PLATINE-BENZACRIDINE FONCTIONNALISTES ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV WAKE FOREST

  公开号：WO2015200172A1

  公开（公告）日：2015-12-30

  The present invention relates to using a versatile synthetic approach to generate a new class of ester, amido, or carbamate prodrugs of highly potent, but systemicaliy too toxic platinum -acridine anticancer agents. The new hybrids contain a hydroxyl group which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2-propanepentanoic (valproic) esters were introduced to these compounds. The goal of this design was to improve the drug-like properties of the pharmacophore (e. g., logD) without compromising its DNA-mediated cell kill potential.

  本发明涉及使用一种多功能合成方法来生成一类新的酯、酰胺或碳酸酯前药，这些前药是高效但系统毒性过高的铂-吖啶抗癌药物。这些新的混合物包含一个被可裂解的亲脂性酰基掩蔽的羟基。这些化合物引入了丁酸（丁酸）和更大的2-丙烷戊酸（丙戊酸）酯。这种设计的目标是改善药物样性质（例如，logD）而不影响其DNA介导的细胞杀伤潜力。
• Design of Enzymatically Cleavable Prodrugs of a Potent Platinum-Containing Anticancer Agent
  作者：Song Ding、Amanda J. Pickard、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1002/chem.201404675

  日期：2014.12.1

  approach, a new class of potential ester prodrugs of highly potent, but systemically too toxic, platinum–acridine anticancer agents was generated. The new hybrids contain a hydroxyl group, which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2‐propanepentanoic (valproic) esters were introduced. The goals of this design were to improve the drug‐like properties

  使用一种通用的合成方法，产生了一类新的潜在酯类前药，它们是高效但全身毒性过大的铂-吖啶抗癌剂。新的杂化物含有一个羟基，它被一个可裂解的亲脂酰基部分掩盖。引入了丁酸（丁酸）和体积更大的 2-丙戊酸（丙戊酸）酯。该设计的目标是改善药物样特性（例如 log D) 并降低药效团的全身毒性。目标化合物进行有效酯水解的两种不同途径，即所提议的活化步骤，已得到证实：铂辅助、低氯化物环境中的自焚酯裂解（LC-ESMS、NMR 光谱）和人类酶促裂解羧酸酯酶-2 (hCES-2) (LC-ESMS)。丙戊酸酯衍生物是第一个可被前药转化酶切割的含金属试剂的例子。它们显示出优异的化学稳定性和降低的全身毒性。肺腺癌细胞系 (A549, NCI-H1435) 筛选的初步结果表明，丙戊酸酯的机制可能涉及细胞内去酯化。
• Synthesis and Pharmacological Evaluation of Modified Adenosines Joined to Mono-Functional Platinum Moieties
  作者：Stefano D'Errico、Giorgia Oliviero、Nicola Borbone、Vincenzo Piccialli、Brunella Pinto、Francesca De Falco、Maria Maiuri、Rosa Carnuccio、Valeria Costantino、Fabrizia Nici、Gennaro Piccialli

  DOI：10.3390/molecules19079339

  日期：——

  The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyl)adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.

  本研究报道了四种新型铂配合物的合成，它们分别以 N6-(6-氨基-己基)腺苷或 1,6-二(腺苷-N6-基)己烷作为单功能顺铂或单氯(乙基二胺)铂(II)的配体。这种化学方法利用了带电铂中心对腺苷碱基系统 N7 位和安装在嘌呤 C6 位上的烷基链伯胺的高亲和力。在 A549 腺癌人肺泡基底上皮细胞系和 MCF7 人乳腺癌腺癌细胞系中研究了合成复合物的细胞毒性行为，以了解它们对细胞活力和增殖的影响。
• A novel approach to site-specifically platinated oligonucleotides applying combinations of nucleobase protecting groups
  作者：Robert J. Heetebrij、Reynier A. Tromp、Gijs A. van der Marel、Jacques H. van Boom、Jan Reedijk

  DOI：10.1039/a904365i

  日期：——

  Platination of a properly protected oligonucleotide followed by deprotection represents a new method for the synthesis of site-specific platinum-modified nucleic acids; N7 platination of 2′-deoxyguanosine can be circumvented by introducing a bulky protective group at the O6 position.

  对经过适当保护的寡核苷酸进行铂化后再去保护，是合成特定位点铂修饰核酸的一种新方法；通过在 O6 位引入一个大的保护基团，可以避免 2′-脱氧鸟苷的 N7 铂化。
• New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities
  作者：Andjela A. Franich、Marija D. Živković、Tatjana Ilić-Tomić、Ivana S. Đorđević、Jasmina Nikodinović-Runić、Aleksandar Pavić、Goran V. Janjić、Snežana Rajković

  DOI：10.1007/s00775-020-01770-7

  日期：2020.5

  interact with the phosphate backbone forming DNA-Pt adducts with an unique and previously undescribed binding mode, called a minor groove covering. The results of this study suggested that the new binding mode of the aqua-Pt(II) complexes with DNA could be attributed to the higher anticancer activities of their chloride analogues. All three compounds, particularly complex [Pt(en)Cl}2(μ-4,4′-bipy)]Cl2·2H2O

  新的抗癌铂（II）化合物同时靶向肿瘤细胞和肿瘤衍生的新血管生成，具有新的DNA相互作用模式和宽大的治疗窗口，是提高临床铂化学疗法疗效的诱人选择。在这里，我们描述了三种新型双核[PT（en）Cl} 2（μ- L）] 2+配合物，它们具有不同的吡啶样桥联配体（L），4,4'-联吡啶（PT1），1,2-双（4-吡啶基）乙烷（P t2中）和1,2-双（4-吡啶基）乙烯（PT3） ，其高度，带正电荷的AQUA衍生物，[铂（烯）（H 2 O）} 2（μ - L）] 4+，与磷酸盐骨架形成相互作用的DNA-PT加合物，具有独特的，以前未描述的结合方式，称为小沟覆盖。这项研究的结果表明，aqua-PT（II）复合物与DNA的新结合模式可能归因于其氯化物类似物的更高的抗癌活性。所有这三种化合物，特别是复杂的[PT（en）Cl} 2（μ - 4,4'-bipy ）] Cl 2 ·2H 2 O（4,4'-bipy是4