4-(2,6-dimethoxybenzamido)-1H-pyrazole-3-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2,6-dimethoxybenzamido)-1H-pyrazole-3-carboxylic acid
• 英文别名: 4-[(2,6-dimethoxybenzoyl)amino]-1H-pyrazole-5-carboxylic acid
• 化学式: C₁₃H₁₃N₃O₅
• 分子量: 291.263
• InChiKey: KWLUBAIPGBORKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2,6-dimethoxybenzamido)-1H-pyrazole-3-carboxylic acid 、 1-氨基戊烷 在 1-羟基苯并三唑 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以84%的产率得到4-(2,6-dimethoxybenzamido)-N-pentyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  The Design and Synthesis of Potent and Selective Inhibitors of Trypanosoma brucei Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis

  摘要：

  Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Tiypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3 beta enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture.

  DOI：

  10.1021/jm500239b
• 作为产物：
  描述：

  methyl 4-(2,6-dimethoxybenzamido)-1H-pyrazole-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 以89%的产率得到4-(2,6-dimethoxybenzamido)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  The Design and Synthesis of Potent and Selective Inhibitors of Trypanosoma brucei Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis

  摘要：

  Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Tiypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3 beta enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture.

  DOI：

  10.1021/jm500239b

文献信息

• The Design and Synthesis of Potent and Selective Inhibitors of <i>Trypanosoma brucei</i> Glycogen Synthase Kinase 3 for the Treatment of Human African Trypanosomiasis
  作者：Robert Urich、Raffaella Grimaldi、Torsten Luksch、Julie A. Frearson、Ruth Brenk、Paul G. Wyatt

  DOI：10.1021/jm500239b

  日期：2014.9.25

  Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Tiypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3 beta enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture.