ethyl 1-(4-fluorophenyl)-5-phenyl-1H-pyrazole-3-carboxylate | 781663-68-1

• 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-(4-fluorophenyl)-5-phenyl-1H-pyrazole-3-carboxylate
• 英文别名: 3-ethoxycarbonyl-1-(4-fluorophenyl)-5-phenyl-1H-pyrazole；Ethyl 1-(4-fluorophenyl)-5-phenylpyrazole-3-carboxylate
• CAS: 781663-68-1
• 化学式: C₁₈H₁₅FN₂O₂
• 分子量: 310.328
• InChiKey: MPYMIALAJAXCFZ-UHFFFAOYSA-N

物化性质

• 沸点：
  458.9±40.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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-(4-fluorophenyl)-5-phenyl-1H-pyrazole-3-carboxylate 在 锂硼氢 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 87.5h， 生成 3-bromomethyl-1-(4-fluorophenyl)-5-phenyl-1H-pyrazole
  参考文献：
  名称：

  New COX-2/5-LOX Inhibitors:  Apoptosis-Inducing Agents Potentially Useful in Prostate Cancer Chemotherapy

  摘要：

  The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.

  DOI：

  10.1021/jm0407761
• 作为产物：
  描述：

  4-氟苯肼 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 1.0h， 生成 ethyl 1-(4-fluorophenyl)-5-phenyl-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Ca v 3.1选择性T型钙通道阻滞剂的发现和评估

  摘要：

  我们确定并表征了一系列吡唑酰胺，它们是有效的，选择性的Ca v 3.1阻滞剂。该系列最终鉴定出吡唑酰胺5a和12d，对Ca v 3.2-和Ca v 3.3通道具有出色的效能和/或选择性。该化合物显示差的DMPK特性，使其难以在体内应用。然而，该化合物以及类似化合物都非常适合进行体外研究。

  DOI：

  10.1016/j.bmcl.2017.09.063

文献信息

• 10.1021/acs.jmedchem.4c00831
  作者：Shi, Shaochun、Ma, Dingchen、Guo, Ximing、Chen, Yu、Yu, Jinying、Hu, Xiao、Wang, Xuan、Li, Ting、Wang, Ke、Zhi, Yunbao、Yang, Guoqing、Lin, Lizhi、Hao, Qingjing、Yang, Yuqiao、Yang, Kan、Wang, Jinxin

  DOI：10.1021/acs.jmedchem.4c00831

  日期：——

  confirmed that acid sphingomyelinase (ASM) activity is associated with depression. The discovery of direct inhibitors against ASM is of great significance for exploring antidepressants and their mechanisms of action. Herein, a series of novel phenylpyrazole analogues were rationally designed and synthesized. Among them, compound 46 exhibited potent inhibitory activity (IC50 = 0.87 μM) and good drug-like properties

  多项研究已证实酸性鞘磷脂酶 (ASM) 活性与抑郁症相关。 ASM直接抑制剂的发现对于探索抗抑郁药物及其作用机制具有重要意义。本文合理设计并合成了一系列新型苯基吡唑类似物。其中，化合物46表现出有效的抑制活性（IC 50 = 0.87 μM）和良好的药物样特性。体内研究表明，化合物46参与多种抗抑郁作用机制，这些机制与神经酰胺的下降有关，包括增加 Bcl-2/Bax 比率和 BDNF 表达，下调 caspase-3 和 caspase-9，改善氧化应激，降低小鼠大脑中促炎细胞因子（如 TNF-α、IL-1β 和 IL-6）的水平，以及升高 5-HT 水平。这些有意义的结果首次揭示了直接抑制剂通过多种抗抑郁作用机制在 CUMS 诱导的小鼠模型中表现出显着的抗抑郁作用。
• Palladium-Catalyzed Chelation-Assisted Regioselective Oxidative Dehydrogenative Homocoupling/<i>Ortho</i>-Hydroxylation in <i>N</i>-Phenylpyrazoles
  作者：Harikrishna Batchu、Soumya Bhattacharyya、Ruchir Kant、Sanjay Batra

  DOI：10.1021/acs.joc.5b00733

  日期：2015.8.7

  A palladium-catalyzed pyrazole-directed regioselective oxidative C(sp2)-H functionalization of the N-phenyl ring in N-phenylpyrazoles to afford either a biaryl bis-pyrazole (via dehydrogenative homocoupling) or N-(o-hydroxyphenyl)pyrazole (via C-H oxygenation) or their mixture is described. The substitutions on the N-phenyl ring and the pyrazole ring and the dilution of the reaction medium with respect to the TFA/TFAA mixture (substrate concentration) have a remarkable influence on the outcome of the reaction. It was discovered that if the reactions were performed under highly dilute conditions (ca. 10 times) then N-(o-hydroxyphenyl)pyrazoles were the major or the sole products.
• A new efficient synthesis of pyrazoles from hydrazonoyl halides and β-oxophosphonates
  作者：Aixue Sun、Jia-Hai Ye、Haitao Yu、Wenchao Zhang、Xiaolong Wang

  DOI：10.1016/j.tetlet.2013.12.045

  日期：2014.1

  A new practical and efficient synthesis of 1,3,5-trisubstituted pyrazoles has been developed by reacting of hydrazonoyl halides with beta-oxophosphonates under mild conditions in good yields with excellent regioselectivity. This process employs an addition-elimination sequence. Wide scope, functional group compatibility has been established. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of vicinal-Diaryl Pyrazole Ethyl Carboxylate Analogs as Antiproliferative Agent against Pancreatic Cancer
  作者：Sandeep Singh、Rajeev Kumar Sharma、Aishwarya Singh、Manoj Garg、R. Ramajayam

  DOI：10.14233/ajchem.2024.31173

  日期：——

  vicinal Diaryl scaffold possessing various heterocycles displayed versatile pharmacological activities ranging from antibacterial to antiviral. Herein, the synthesis of novel vicinal diaryl pyrazole ethyl carboxylate analogs as central ring and evaluated for their antiproliferative activity against pancreatic cancer line, PANC-1. Among the synthesized 27 compounds, six compounds displayed the IC50 value for antiproliferative activity in single digit micromolar. The cytotoxicity results of the synthesized compounds especially compound 25 (IC50 = 4.8 µM) confirms that these analogs may require further investigation.
• New COX-2/5-LOX Inhibitors:  Apoptosis-Inducing Agents Potentially Useful in Prostate Cancer Chemotherapy
  作者：Nicole Pommery、Thierry Taverne、Aurélie Telliez、Laurence Goossens、Caroline Charlier、Jean Pommery、Jean-François Goossens、Raymond Houssin、François Durant、Jean-Pierre Hénichart

  DOI：10.1021/jm0407761

  日期：2004.12.1

  The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.