di-2-pyridylketone 4-ethyl-4-methyl-3-thiosemicarbazone hydrochloride | 1382469-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: di-2-pyridylketone 4-ethyl-4-methyl-3-thiosemicarbazone hydrochloride
• 英文别名: 3-(Dipyridin-2-ylmethylideneamino)-1-ethyl-1-methylthiourea;hydrochloride
• CAS: 1382469-42-2
• 化学式: C₁₅H₁₇N₅S*ClH
• 分子量: 335.86
• InChiKey: PAWPGTPEMYUSRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  85.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  di-2-pyridylketone 4-ethyl-4-methyl-3-thiosemicarbazone 在 盐酸 作用下， 以 水 、 甲苯 为溶剂， 以91%的产率得到di-2-pyridylketone 4-ethyl-4-methyl-3-thiosemicarbazone hydrochloride
  参考文献：
  名称：

  Novel Second-Generation Di-2-Pyridylketone Thiosemicarbazones Show Synergism with Standard Chemotherapeutics and Demonstrate Potent Activity against Lung Cancer Xenografts after Oral and Intravenous Administration in Vivo

  摘要：

  We developed a series of second-generation di-2-pyridyl ketone thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands to improve the efficacy safety profile of these potential antitumor agents. Two novel DpT analogues, Dp4e4mT and DpC, exhibited pronounced and selective activity against human lung cancer xenografts in vivo via the intravenous and oral routes. Importantly, these analogues did not induce the cardiotoxicity observed at high nonoptimal doses of the first-generation DpT analogue, Dp44mT. The Cu(II) complexes of these ligands exhibited potent antiproliferative activity having redox potentials in a range accessible to biological reductants. The activity of the copper complexes of Dp4e4mT and DpC against lung cancer cells was synergistic in combination with gemcitabine or cisplatin. It was demonstrated by EPR spectroscopy that dimeric copper compounds of the type [CuLCl](2), identified crystallographically, dissociate in solution to give monomeric 1:1 Cu:ligand complexes. These monomers represent the biologically active form of the complex.

  DOI：

  10.1021/jm300768u

文献信息

• [EN] THIOSEMICARBAZONE COMPOUNDS AND USE IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS DE THIOSEMICARBAZONE ET UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：RICHARDSON DES R

  公开号：WO2012079128A1

  公开（公告）日：2012-06-21

  The present invention relates to dipyridyl thiosemicarbazone compounds of formula (I): wherein R1 is cyclohexyl or ethyl; as well as pharmaceutical compositions containing those compounds, and the use of those compounds and compositions in the treatment of cancer.

  本发明涉及式(I)的二吡啶基硫脲酮化合物，其中R1为环己基或乙基；以及含有这些化合物的药物组合物，以及这些化合物和组合物在癌症治疗中的应用。
• THIOSEMICARBAZONE COMPOUNDS AND USE IN THE TREATMENT OF CANCER
  申请人：Richardson, Des R

  公开号：EP2651894A1

  公开（公告）日：2013-10-23
• US8927580B2
  申请人：——

  公开号：US8927580B2

  公开（公告）日：2015-01-06
• Novel Second-Generation Di-2-Pyridylketone Thiosemicarbazones Show Synergism with Standard Chemotherapeutics and Demonstrate Potent Activity against Lung Cancer Xenografts after Oral and Intravenous Administration in Vivo
  作者：David B. Lovejoy、Danae M. Sharp、Nicole Seebacher、Peyman Obeidy、Thomas Prichard、Christian Stefani、Maram T. Basha、Philip C. Sharpe、Patric J. Jansson、Danuta S. Kalinowski、Paul V. Bernhardt、Des R. Richardson

  DOI：10.1021/jm300768u

  日期：2012.8.23

  We developed a series of second-generation di-2-pyridyl ketone thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands to improve the efficacy safety profile of these potential antitumor agents. Two novel DpT analogues, Dp4e4mT and DpC, exhibited pronounced and selective activity against human lung cancer xenografts in vivo via the intravenous and oral routes. Importantly, these analogues did not induce the cardiotoxicity observed at high nonoptimal doses of the first-generation DpT analogue, Dp44mT. The Cu(II) complexes of these ligands exhibited potent antiproliferative activity having redox potentials in a range accessible to biological reductants. The activity of the copper complexes of Dp4e4mT and DpC against lung cancer cells was synergistic in combination with gemcitabine or cisplatin. It was demonstrated by EPR spectroscopy that dimeric copper compounds of the type [CuLCl](2), identified crystallographically, dissociate in solution to give monomeric 1:1 Cu:ligand complexes. These monomers represent the biologically active form of the complex.