e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-dihydroxo-b,c-dichloroplatinum(II) | 764645-96-7

• 英文名称: e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-dihydroxo-b,c-dichloroplatinum(II)
• 英文别名: e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-dihydroxo-b,c-dichloroplatinum(IV)；cis,trans,cis-Pt(2,2,6,6-tetramethyl-1-oxyl-4-piperidinylNH2)(NH3)(OH)2Cl2
• CAS: 764645-96-7
• 化学式: C₉H₂₄Cl₂N₃O₃Pt
• 分子量: 488.294
• InChiKey: IWQPEBYBEBNKBN-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
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• 重原子数：
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• 可旋转键数：
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• 环数：
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• sp3杂化的碳原子比例：
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• 拓扑面积：
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• 氢给体数：
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• 氢受体数：
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反应信息

• 作为反应物：
  描述：

  e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-dihydroxo-b,c-dichloroplatinum(II) 在 HCl 作用下， 以 乙醇 为溶剂， 生成 cis,trans,cis-Pt(Me4C5H5NOH)(NH3)(OH)2Cl2
  参考文献：
  名称：

  摘要：

  The platinum(IV) complexes cis,trans,cis-Pt-IV(RNH2)(NH3)(OH)(2)Cl-2, where R is 2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl (1) or 2,2,5,5-tetramethyl-1-oxyl-3-pyrrolidinyl (2), were prepared by oxidation of the corresponding cis-Pt-II(RNH2)(NH3)Cl-2 complexes with hydrogen peroxide. The reactions are catalyzed by tungstate salts, which makes it possible to carry out oxidation under mild conditions. The resulting complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectroscopy. The structure of complex 1 was established by X-ray diffraction analysis. Complex 1 exhibits the highest antitumor activity in an experimental tumor, viz., in P388 leukemia. The resistance of the tumor to this complex developed much slower than that to Cisplatin.

  DOI：

  10.1023/a:1023475319835
• 作为产物：
  描述：

  cis-ammine(4-amino-2,2,6,6-tetramethylpiperidine)dichloroplatinum(II) 在 potassium tungstate H₂O₂ 作用下， 以 水 为溶剂， 生成 e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-dihydroxo-b,c-dichloroplatinum(II)
  参考文献：
  名称：

  摘要：

  The platinum(IV) complexes cis,trans,cis-Pt-IV(RNH2)(NH3)(OH)(2)Cl-2, where R is 2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl (1) or 2,2,5,5-tetramethyl-1-oxyl-3-pyrrolidinyl (2), were prepared by oxidation of the corresponding cis-Pt-II(RNH2)(NH3)Cl-2 complexes with hydrogen peroxide. The reactions are catalyzed by tungstate salts, which makes it possible to carry out oxidation under mild conditions. The resulting complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectroscopy. The structure of complex 1 was established by X-ray diffraction analysis. Complex 1 exhibits the highest antitumor activity in an experimental tumor, viz., in P388 leukemia. The resistance of the tumor to this complex developed much slower than that to Cisplatin.

  DOI：

  10.1023/a:1023475319835

文献信息

• Synthesis and antitumor properties of new platinum(IV) complexes with aminonitroxyl radicals
  作者：V. D. Sen’、V. A. Golubev、N. Yu. Lugovskaya、T. E. Sashenkova、N. P. Konovalova

  DOI：10.1007/s11172-006-0215-1

  日期：2006.1

  Acylation of cis,trans,cis-PtIV(RNH2)(NH3)(OH)2Cl2 with acetic anhydride afforded complexes cis,trans,cis-PtIV(RNH2)(NH3)(OAc)2Cl2, where R is 2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl (1b) or 2,2,5,5-tetramethyl-1-oxylpyrrolidin-3-yl (2b). The complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectra. Complex 1b exhibits high antitumor activity comparable with that of Cisplatin against leukemia P388 used as the experimental tumor. Simultaneous administration of low doses of 1b and Cisplatin (1/20 of LD50 each) results in synergism of the antitumor activity and 100% cure of animals.

  顺式、反式、顺式-PtIV(RNH2)(NH3)(OH)2Cl2与乙酸酐的酰化反应生成顺式、反式、顺式-PtIV(RNH2)(NH3)(OAc)2Cl2的络合物，其中R为2,2,6,6-四甲基-1-氧代哌啶-4-基（1b）或2,2,5,5-四甲基-1-氧代吡咯烷-3-基（2b）。通过元素分析、HPLC、IR、UV和ESR光谱对络合物进行表征。络合物1b表现出与顺铂相当的抗肿瘤活性，可用于治疗白血病P388。同时给予低剂量的1b和顺铂（各为LD50的1/20）可产生协同抗肿瘤活性，并使动物100%治愈。
• Synergistic antitumor effect of cisplatin and the platinum(iv) nitroxyl complex BC118 and the development of resistance to their combined action
  作者：S. A. Goncharova、T. A. Raevskaya、T. N. Yakushchenko、S. V. Blokhina、N. P. Konovalova、V. D. Sen’

  DOI：10.1007/s11172-011-0293-6

  日期：2011.9

  The efficacy of the combination treatment of P388 leukemia with cisplatin (cPt) and the platinum(IV) nitroxyl complex BC118 [e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bis(acetato)-b,c-dichloroplatinum(iv)] applied in low doses was found to be synergistically increased. Thus, the use of 1/10 of their LD50 cured 100% of animals. The monotherapy with these drugs used in the same doses and at the same schedules showed moderate efficacy, and no animals survived. A synergistic increase in the toxicity was not observed. The rate of the development of resistance decreases in the series cPt+BC118, cPt, and BC118. Strains resistant to cPt+BC118 and BC118 are highly sensitive to doxorubicin, etoposide, and cyclophosphane.

  P388白血病与顺铂（cPt）和低剂量铂（IV）硝基络合物BC118（e-氨-d-(4-氨基-2,2,6,6-四甲基哌啶-1-氧基)-a,f-双（乙酸基）-b,c-二氯铂（IV））联合治疗的疗效被证实具有协同增效作用。因此，使用1/10的LD50剂量即可治愈100%的动物。以相同剂量和相同方案使用这些药物的单药疗法显示出中等疗效，没有动物存活。没有观察到毒性协同增加。在cPt+BC118、cPt和BC118系列中，耐药性的发展速度降低。对cPt+BC118和BC118具有抗性的菌株对阿霉素、依托泊苷和环磷酰胺高度敏感。
• Synthesis, structure, and cytotoxicity of platinum(iv) complexes bearing aminoxyl and dichloroacetate ligands
  作者：V. D. Sen’、N. V. Filatova、G. V. Shilov、A. A. Terentiev

  DOI：10.1007/s11172-023-3948-1

  日期：2023.7

  New platinum(iv)-aminoxyl complexes (PACs) 2a,b, bearing an aminoxyl radical with antioxidant properties in the equatorial position and axial dichloroacetate ligands capable of inhibiting the energy production in tumor cells through aerobic glycolysis were synthesized. Complexes 2a,b are characterized by moderate lipophilicity (log Pow ∼2) and differ in the redox properties of aminoxyls. The cytotoxicity

  合成了新的铂( iv )-氨氧基络合物(PAC) 2a,b，其在赤道位置带有具有抗氧化特性的氨氧基自由基，并且轴向二氯乙酸酯配体能够通过有氧糖酵解抑制肿瘤细胞中的能量产生。配合物2a、b具有中等亲脂性（log P ow ∼2），并且与氨氧基的氧化还原特性不同。研究了复合物2a、b对肿瘤（HeLa、HepG2、MCF-7）和非癌细胞 Vero 的细胞毒性，并与顺铂 (CP)、沙铂 (JM216) 和之前描述的带有轴向乙酸盐配体的 PNC 3a、b进行比较。2a、b的细胞毒性对于肿瘤细胞的IC 50 (IC 50 19–171 µmol L -1 )比复合物3a,b高2–11倍，并且与CP和JM216的IC 50值(10–187 µmol L -1 )相当。对于非癌细胞 Vero，2a,b (62–124 µmol L -1 ) 的细胞毒性显着低于 CP 和 JM216 (17.6–33 µmol