1-(4-(methylthio)phenyl)-5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazole | 616209-43-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-(methylthio)phenyl)-5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazole
• 英文别名: 1-(4-(methylthio)phenyl)-5-p-tolyl-3-(trifluoromethyl)-1H-pyrazole；5-(4-methylphenyl)-1-(4-methylsulfanylphenyl)-3-(trifluoromethyl)pyrazole
• CAS: 616209-43-9
• 化学式: C₁₈H₁₅F₃N₂S
• 分子量: 348.392
• InChiKey: FSNCQAFYBNJJDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-(methylthio)phenyl)-5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazole 在 叔丁基过氧化氢 、 camphor-10-sulfonic acid 作用下， 以 二氯甲烷 、 various solvents 为溶剂， 反应 4.0h， 以87%的产率得到1-(4-Methanesulfinyl-phenyl)-5-p-tolyl-3-trifluoromethyl-1H-pyrazole
  参考文献：
  名称：

  CYP2C9 Structure−Metabolism Relationships:  Optimizing the Metabolic Stability of COX-2 Inhibitors

  摘要：

  The cytochrome P450 (CYP) family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. CYP2C9, one of the major isoforms of the CYP family, is responsible for the phase I metabolism of a variety of drugs. The aim of the present investigation is to use rational design together with MetaSite, a metabolism site prediction program, to synthesize compounds that retain their pharmacological effects but that are metabolically more stable in the presence of CYP2C9. The model compound for the study is the nonsteroidal anti-inflammatory drug celecoxib, a COX-2 selective inhibitor and known CYP2C9 substrate. Thirteen analogs of celecoxib were designed, synthesized, and evaluated with regard to their metabolic properties and pharmacologic effects. The docking solutions and the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties.

  DOI：

  10.1021/jm0705096
• 作为产物：
  描述：

  4-氨基茴香硫醚 在 盐酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.58h， 生成 1-(4-(methylthio)phenyl)-5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  CYP2C9 Structure−Metabolism Relationships:  Optimizing the Metabolic Stability of COX-2 Inhibitors

  摘要：

  The cytochrome P450 (CYP) family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. CYP2C9, one of the major isoforms of the CYP family, is responsible for the phase I metabolism of a variety of drugs. The aim of the present investigation is to use rational design together with MetaSite, a metabolism site prediction program, to synthesize compounds that retain their pharmacological effects but that are metabolically more stable in the presence of CYP2C9. The model compound for the study is the nonsteroidal anti-inflammatory drug celecoxib, a COX-2 selective inhibitor and known CYP2C9 substrate. Thirteen analogs of celecoxib were designed, synthesized, and evaluated with regard to their metabolic properties and pharmacologic effects. The docking solutions and the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties.

  DOI：

  10.1021/jm0705096

文献信息

• Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
  作者：Tristan Delcaillau、Philip Boehm、Bill Morandi

  DOI：10.1021/jacs.1c00529

  日期：2021.3.17

  We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications

  我们描述了芳基腈和芳基硫醚之间的新官能团复分解。催化系统镍/dcype 对于实现这种完全可逆的转化，以良好的收率至关重要。此外，不含氰化物和硫醇的反应显示出高官能团耐受性和商业分子后期衍生化的高效率。最后，合成应用证明了它在多步合成中的多功能性和实用性。
• Nickel-Catalyzed Cross-Coupling Reaction of Aryl Methyl Sulfides with Aryl Bromides
  作者：Chuntao Zhong、Mengna Liu、Xianchao Qiu、Hao Wei、Benqiang Cui、Yanhui Shi、Changsheng Cao

  DOI：10.1021/acs.joc.3c00630

  日期：2023.10.6

  A nickel-catalyzed cross-coupling reaction of aryl methyl sulfides with aryl bromides has been developed to access biaryls in yields of up to 86%. The reactions proceeded well using Ni(COD)2 as catalyst with the ligand BINAP (2,2′-bis(diphenylphosphanyl)-1,1′-binaphthalene) in the presence of magnesium. The method has a broad scope of substrates and is scalable. The wide availability of commercially

  镍催化的芳基甲基硫醚与芳基溴化物的交叉偶联反应已被开发出来，可以以高达 86% 的产率获得联芳基化合物。使用 Ni(COD) 2作为催化剂，配体 BINAP（2,2'-双（二苯基膦基）-1,1'-联萘）在镁存在下反应进展顺利。该方法具有广泛的底物范围并且可扩展。市售芳基溴的广泛可用性以及有机金属试剂的制备和制备的缺乏使得该反应具有很高的应用价值。
• CYP2C9 Structure−Metabolism Relationships:  Optimizing the Metabolic Stability of COX-2 Inhibitors
  作者：Marie M. Ahlström、Marianne Ridderström、Ismael Zamora、Kristina Luthman

  DOI：10.1021/jm0705096

  日期：2007.9.1

  The cytochrome P450 (CYP) family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. CYP2C9, one of the major isoforms of the CYP family, is responsible for the phase I metabolism of a variety of drugs. The aim of the present investigation is to use rational design together with MetaSite, a metabolism site prediction program, to synthesize compounds that retain their pharmacological effects but that are metabolically more stable in the presence of CYP2C9. The model compound for the study is the nonsteroidal anti-inflammatory drug celecoxib, a COX-2 selective inhibitor and known CYP2C9 substrate. Thirteen analogs of celecoxib were designed, synthesized, and evaluated with regard to their metabolic properties and pharmacologic effects. The docking solutions and the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties.