Ethyl 1-(2-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 1-(2-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylate
• 英文别名: ethyl 1-(2-fluorophenyl)-5-methylpyrazole-4-carboxylate
• 化学式: C₁₃H₁₃FN₂O₂
• mdl: MFCD04122755
• 分子量: 248.257
• InChiKey: VDCILVIEIZCRQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 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：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 1-(2-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylate 在 chloro-N,N,N',N'-bis(tetramethylene)formamidinium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 1-(2-fluorophenyl)-5-methyl-N-(quinolin-2-yl)-1H-pyrazole-4-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：

  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 Ethyl 1-(2-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylate
  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

• Potential Fungicide Candidates: A Dual Action Mode Study of Novel Pyrazole-4-carboxamides against <i>Gibberella zeae</i>
  作者：Chengzhi Zhang、Jingxin Yang、Cailong Zhao、Longju Li、Zhibing Wu

  DOI：10.1021/acs.jafc.2c06962

  日期：2023.2.1

  2%, respectively. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis revealed that the large steric hindrance and electronegative groups on the 5-position of the pyrazole ring were important for the activity. The IC50 value of Y47 against succinate dehydrogenase (SDH) was 7.7 mg/L, superior to fluopyram (24.7 mg/L), which was consistent with the docking results. Morphological

  吡唑甲酰胺是一类传统的琥珀酸脱氢酶抑制剂 (SDHI)，已发展成为多种商业化杀菌剂。在目前的工作中，基于 5-trifluoromethyl-1 H -4-pyrazole carboxamide的活性主链，设计并合成了一系列新型 1,5-disubstituted-1 H -pyrazole-4-carboxamide 衍生物。生物测定结果表明，一些目标化合物对六种植物病原真菌表现出优异的体外抗真菌活性。值得注意的是，Y 47对玉米赤霉菌、米黑孢菌、黄瓜炭疽菌和黄萎病大丽花分别为 5.2、9.2、12.8 和 17.6 mg/L。100 mg/L的Y 47对玉米上的G. zeae的体内保护和治疗活性分别为 50.7 和 44.2%。三维定量构效关系 (3D-QSAR) 分析表明，吡唑环 5 位上的大空间位阻和电负性基团对该活性很重要。Y 47的IC 50值抗琥珀酸脱氢酶（SDH）为7.7