N,N-二甲基-N'-(5-硝基喹啉-4-基)丙烷-1,3-二胺 | 80552-29-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: N,N-二甲基-N'-(5-硝基喹啉-4-基)丙烷-1,3-二胺
• 英文名称: 5-nitro-4-(N,N-dimethylaminopropylamino)quinoline
• 英文别名: 5-nitraquine；1,3-Propanediamine, N,N-dimethyl-N'-(5-nitro-4-quinolinyl)-；N',N'-dimethyl-N-(5-nitroquinolin-4-yl)propane-1,3-diamine
• CAS: 80552-29-0
• 化学式: C₁₄H₁₈N₄O₂
• 分子量: 274.323
• InChiKey: OYBQBXGOFWWPTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-5-硝基-喹啉 、 N,N-二甲基-1,3-二氨基丙烷 反应 1.5h， 以65%的产率得到N,N-二甲基-N'-(5-硝基喹啉-4-基)丙烷-1,3-二胺
  参考文献：
  名称：

  Hypoxia-selective antitumor agents. 6. 4-(Alkylamino)nitroquinolines: a new class of hypoxia-selective cytotoxins

  摘要：

  A series of isomeric 4-[[3-(dimethylamino)propyl]amino]nitroquinolines has been synthesized and evaluated as hypoxia-selective cytotoxins and as radioeensitizers of hypoxic cells. The compounds showed widely-differing hypersensitivity factors (ratios of cytotoxicity against wild-type and repair-deficient mammalian cells). Many compounds showed oxygen-sensitive bioreduction resulting in DNA alkylation, while others show oxygen-insensitive modes of action. Of the nitro isomers studied, the 5-nitro showed the greatest hypoxic selectivity. A series of ring-substituted analogues were then prepared, in an effort to lower its reduction potential of -286 mV. Structure-activity studies showed that the effects of substitution on reduction potential were complex, being mediated by electronic and steric effects on the nitro group, as well as by effects on quinoline pK(a). Two compounds of lower reduction potential, the 3- and 8-methyl analogues, showed improved selectivity (47- and 60-fold in a clonogenic assay). These two compounds also showed the highest ''in vitro therapeutic indices'' of the series as hypoxic cell radiosensitizers. Despite these favorable in vitro properties, neither compound had activity against hypoxic cells in SCCVII tumors when administered at 60% of the MTD.

  DOI：

  10.1021/jm00104a008

文献信息

• [EN] METHODS AND COMPOSITIONS TO IMPROVE ACTIVITY AND REDUCE TOXICITY OF STENTS<br/>[FR] METHODES ET COMPOSITIONS AMELIORANT L'ACTIVITE ET REDUISANT LA TOXICITE DE STENTS
  申请人：AU JESSIE L S

  公开号：WO2007065016A2

  公开（公告）日：2007-06-07

  [EN] Disclosed is a method of improving the efficacy of endovascular drug- releasing stents implanted in a subject, wherein one or more modulators of drug transport are administered at such a time as is beneficial to maintain nearby tissue concentrations of the drug released by the stent within their therapeutically effective range, wherein one or more modulators of drug activity are administered at such a time as is beneficial to prevent restenosis, and wherein one or more modulators of drug activity are administered at such a time as is beneficial to promote the early healing or reendothelialization process.
  [FR] L'invention porte sur une méthode améliorant l'efficacité de stents endovasculaires libérant des médicaments, implantés dans un patient. On peut administrer à cet effet: un ou des modulateurs de transport du médicament à des moments opportuns pour maintenir une concentration, dans les tissus voisins du médicament libéré par le stent, dans ses limites d'efficacité thérapeutique; un ou des modulateurs de l'activité du médicament pour prévenir les resténoses; et un ou des modulateurs de l'activité du médicament à des moments opportuns pour promouvoir la cicatrisation rapide ou le processus de réendothélialisation.
• Hypoxia-selective antitumor agents. 6. 4-(Alkylamino)nitroquinolines: a new class of hypoxia-selective cytotoxins
  作者：William A. Denny、Graham J. Atwell、Peter B. Roberts、Robert F. Anderson、Maruta Boyd、Colin J. L. Lock、William R. Wilson

  DOI：10.1021/jm00104a008

  日期：1992.12

  A series of isomeric 4-[[3-(dimethylamino)propyl]amino]nitroquinolines has been synthesized and evaluated as hypoxia-selective cytotoxins and as radioeensitizers of hypoxic cells. The compounds showed widely-differing hypersensitivity factors (ratios of cytotoxicity against wild-type and repair-deficient mammalian cells). Many compounds showed oxygen-sensitive bioreduction resulting in DNA alkylation, while others show oxygen-insensitive modes of action. Of the nitro isomers studied, the 5-nitro showed the greatest hypoxic selectivity. A series of ring-substituted analogues were then prepared, in an effort to lower its reduction potential of -286 mV. Structure-activity studies showed that the effects of substitution on reduction potential were complex, being mediated by electronic and steric effects on the nitro group, as well as by effects on quinoline pK(a). Two compounds of lower reduction potential, the 3- and 8-methyl analogues, showed improved selectivity (47- and 60-fold in a clonogenic assay). These two compounds also showed the highest ''in vitro therapeutic indices'' of the series as hypoxic cell radiosensitizers. Despite these favorable in vitro properties, neither compound had activity against hypoxic cells in SCCVII tumors when administered at 60% of the MTD.