5-methyl-1-(o-tolyl)-1H-pyrazole-3-carboxylic acid | 1020724-19-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-methyl-1-(o-tolyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 5-Methyl-1-o-tolyl-1h-pyrazole-3-carboxylic acid；5-methyl-1-(2-methylphenyl)pyrazole-3-carboxylic acid
• CAS: 1020724-19-9
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: ZUJUFJZISJNDTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨基喹啉 、 5-methyl-1-(o-tolyl)-1H-pyrazole-3-carboxylic acid 在 chloro-N,N,N',N'-bis(tetramethylene)formamidinium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 以68%的产率得到5-methyl-N-(quinolin-2-yl)-1-(o-tolyl)-1H-pyrazole-3-carboxamide
  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：

  邻甲苯胺 在 盐酸 、 sodium hydroxide 、 lithium hydroxide 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 16.0h， 生成 5-methyl-1-(o-tolyl)-1H-pyrazole-3-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

文献信息

• Wnt signaling pathway inhibitors for treatments of disease
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US10882841B2

  公开（公告）日：2021-01-05

  Compounds and compositions are provided as inhibitors of the Wnt/β-catenin pathway for the treatment of diseases that implicate the same.

  提供了作为 Wnt/β-catenin 通路抑制剂的化合物和组合物，用于治疗涉及 Wnt/β-catenin 通路的疾病。
• WNT SIGNALING PATHWAY INHIBITORS FOR TREATMENTS OF DISEASE
  申请人：University of Maryland, Baltimore

  公开号：EP3423452A1

  公开（公告）日：2019-01-09
• WNT Signaling Pathway Inhibitors for Treatments of Disease
  申请人：XUE Fengtian

  公开号：US20190071424A1

  公开（公告）日：2019-03-07

  Compounds and compositions are provided as inhibitors of the Wnt/β-catenin pathway for the treatment of diseases that implicate the same.