1-(2,4-二氟苯基)-5-甲基-1H-吡唑-4-羧酸乙酯 | 175135-71-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(2,4-二氟苯基)-5-甲基-1H-吡唑-4-羧酸乙酯
• 中文别名: 1-(2,4-二氟苯基)-5-甲基吡唑-4-羧酸乙酯
• 英文名称: Ethyl 1-(2,4-difluorophenyl)-5-methylpyrazole-4-carboxylate
• CAS: 175135-71-4
• 化学式: C₁₃H₁₂F₂N₂O₂
• mdl: MFCD00067830
• 分子量: 266.247
• InChiKey: WVZDFYXWWMSKSH-UHFFFAOYSA-N

物化性质

• 沸点：
  116-118°C 0,5mm
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933199090
• 安全说明：
  S23,S24/25

反应信息

• 作为反应物：
  描述：

  1-(2,4-二氟苯基)-5-甲基-1H-吡唑-4-羧酸乙酯 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 1-(2,4-difluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation

  摘要：

  Dysregulation of the Wnt/beta-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of beta-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.

  DOI：

  10.1021/acs.jmedchem.9b01252
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 1-(2,4-二氟苯基)-5-甲基-1H-吡唑-4-羧酸乙酯
  参考文献：
  名称：

  Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation

  摘要：

  Dysregulation of the Wnt/beta-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of beta-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.

  DOI：

  10.1021/acs.jmedchem.9b01252

文献信息

• AMIDE COMPOUNDS AND MEDICINAL USE THEREOF
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1176140B1

  公开（公告）日：2004-12-29