α-propionyl-α-(4'-trifluoromethylphenyl)acetonitrile | 182425-73-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: α-propionyl-α-(4'-trifluoromethylphenyl)acetonitrile
• 英文别名: 3-oxo-2-(4-(trifluoromethyl)phenyl)pentanenitrile
• CAS: 182425-73-6
• 化学式: C₁₂H₁₀F₃NO
• 分子量: 241.213
• InChiKey: ZIHAUNOUHPVNDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.86
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  α-propionyl-α-(4'-trifluoromethylphenyl)acetonitrile 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 4-amino-6-ethyl-5-(4-(trifluoromethyl)phenyl)pyrimidin-2(1H)-one
  参考文献：
  名称：

  Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity

  摘要：

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

  DOI：

  10.1021/jm5017895
• 作为产物：
  描述：

  丙酰氯 、 对三氟甲基苯乙腈 在 lithium diisopropyl amide 作用下， 生成 α-propionyl-α-(4'-trifluoromethylphenyl)acetonitrile
  参考文献：
  名称：

  Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity

  摘要：

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

  DOI：

  10.1021/jm5017895

文献信息

• Preparation of 3,4-Substituted-5-Aminopyrazoles and 4-Substituted-2-Aminothiazoles
  作者：Stepan Havel、Prashant Khirsariya、Naresh Akavaram、Kamil Paruch、Benoit Carbain

  DOI：10.1021/acs.joc.8b02655

  日期：2018.12.21

  3,4-Substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles are frequently used intermediates in medicinal chemistry and drug discovery projects. We report an expedient flexible synthesis of 3,4-substituted-5-aminopyrazoles (35 examples), based on palladium-mediated α-arylation of β-ketonitriles with aryl bromides. A library of 4-substituted-2-aminothiazoles (21 examples) was assembled by a

  3,4-取代的5-氨基吡唑和4-取代的2-氨基噻唑是药物化学和药物开发项目中经常使用的中间体。我们报道了基于钯介导的β-酮腈与芳基溴化物的α-芳基化反应的3,4-取代的5-氨基吡唑类化合物的便捷合成（35个例子）。通过使用新制备的，适当保护的4-硼酸-2-氨基噻唑的频哪醇酯和MIDA酯与（杂）芳基卤化物的Suzuki偶联的序列，组装4-取代的2-氨基噻唑的文库（21个实例）。
• Potential Antimalarials. XXII. Some 2,4-Diamino-5-(3- and 4-trifluoromethylphenyl and 3,4-methylenedioxyphenyl)pyrimidines
  作者：GB Barlin、B Kotecka、KH Rieckmann

  DOI：10.1071/ch9960647

  日期：——

  A series of 10 pyrimethamine analogues containing 3'- and 4'-trifluoromethyl and 3',4'-methylenedioxy groups has been prepared and tested for in vitro antimalarial activity against the FC-27 and K-1isolates of Plasmodium falciparum. Several of these compounds were almost as active as pyrimethamine against the drug-sensitive FC-27 isolate, and like pyrimethamine , they were much less active against the drug-resistant K-1 isolate. The 4'-trifluoromethyl compunds, however, showed much smaller differences.

  一系列含有3'-和4'-三氟甲基和3',4'-亚甲二氧基基团的10个嘧啶胺类似物已经制备并针对Plasmodium falciparum的FC-27和K-1菌株进行了体外抗疟活性测试。其中几种化合物对于对药物敏感的FC-27菌株的活性几乎与嘧啶胺相当，而像嘧啶胺一样，它们对于对药物耐药的K-1菌株的活性要低得多。然而，4'-三氟甲基化合物显示出较小的差异。