3-(dimethylamino)picolinaldehyde

• 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: 3-(dimethylamino)picolinaldehyde
• 英文别名: 3-(Dimethylamino)pyridine-2-carbaldehyde；3-(dimethylamino)pyridine-2-carbaldehyde
• 化学式: C₈H₁₀N₂O
• 分子量: 150.18
• InChiKey: DSBRMGGWPNUPEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(dimethylamino)picolinaldehyde 以 乙醇 、 乙腈 为溶剂， 反应 29.0h， 生成 3-(dimethylamino)pyridine-2-carbaldehyde N-methylthiosemicarbazone
  参考文献：
  名称：

  Impact of Stepwise NH₂-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention

  摘要：

  One of the most promising classes of iron chelators are alpha-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the "completely" methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.

  DOI：

  10.1021/acs.jmedchem.6b00342
• 作为产物：
  描述：

  2-bromo-N,N-dimethylpyridin-3-amine 、 N,N-二甲基甲酰胺 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以54%的产率得到3-(dimethylamino)picolinaldehyde
  参考文献：
  名称：

  Impact of Stepwise NH₂-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention

  摘要：

  One of the most promising classes of iron chelators are alpha-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the "completely" methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.

  DOI：

  10.1021/acs.jmedchem.6b00342

文献信息

• HETEROARYL COMPOUNDS AS BTK INHIBITORS AND USES THEREOF
  申请人：Merck Patent GmbH

  公开号：EP3204382A1

  公开（公告）日：2017-08-16
• [EN] HETEROARYL COMPOUNDS AS BTK INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLE SERVANT D'INHIBITEURS DE LA BTK, ET LEURS UTILISATIONS
  申请人：MERCK PATENT GMBH

  公开号：WO2016057500A1

  公开（公告）日：2016-04-14

  The present invention relates to imidazopyridine compounds of formula I, and pharmaceutically acceptable compositions thereof, useful as BTK inhibitors.
• Impact of Stepwise NH₂-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention
  作者：Christian R. Kowol、Walter Miklos、Sarah Pfaff、Sonja Hager、Sebastian Kallus、Karla Pelivan、Mario Kubanik、Éva A. Enyedy、Walter Berger、Petra Heffeter、Bernhard K. Keppler

  DOI：10.1021/acs.jmedchem.6b00342

  日期：2016.7.28

  One of the most promising classes of iron chelators are alpha-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the "completely" methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.