4-(4,4-difluorocyclohexanecarboxamido)-N-(4-methoxycyclohexyl)-1H-pyrazole-3-carboxamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(4,4-difluorocyclohexanecarboxamido)-N-(4-methoxycyclohexyl)-1H-pyrazole-3-carboxamide
• 英文别名: 4-(4,4-difluorocyclohexane-1-carboxamido)-N-((1r,4r)-4-methoxycyclohexyl)-1H-pyrazole-3-carboxamide
• 化学式: C₁₈H₂₆F₂N₄O₃
• 分子量: 384.426
• InChiKey: BCTHVHCUWYGJKE-JOCQHMNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  96.11
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  trans-4-methoxycyclohexanamine 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 37.0h， 生成 4-(4,4-difluorocyclohexanecarboxamido)-N-(4-methoxycyclohexyl)-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

文献信息

• VALPROIC ACID COMPOUNDS AND WNT AGONISTS FOR TREATING EAR DISORDERS
  申请人：Frequency Therapeutics, Inc.

  公开号：US20220133740A1

  公开（公告）日：2022-05-05

  The present invention provides methods for treating diseases and disorders of the ear with valproic acid compounds and Wnt agonists. The present invention further provides kits for the same.
• 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.