2-(4-chlorophenyl)-4-methyl-3-oxopentanenitrile | 91395-71-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-chlorophenyl)-4-methyl-3-oxopentanenitrile
• CAS: 91395-71-0
• 化学式: C₁₂H₁₂ClNO
• 分子量: 221.686
• InChiKey: KENBWTPYJULPQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-4-methyl-3-oxopentanenitrile 在 碳酸氢钠 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 生成 5-(4-chlorophenyl)-6-isopropylpyrimidine-2,4-diamine
  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：

  3-(4-氯苯基)-1,1-二甲基丙-2-炔-1-醇 在 silver(I) acetate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯碳四(五氟苯基)硼酸盐 作用下， 以 1,2-二氯乙烷 、 甲苯 为溶剂， 80.0 ℃ 、2.0 MPa 条件下， 反应 4.0h， 生成 2-(4-chlorophenyl)-4-methyl-3-oxopentanenitrile 、 4-(4-chlorophenyl)-2,2-dimethyl-3-oxobutanenitrile
  参考文献：
  名称：

  路易斯酸催化的环烯醇碳酸酯的脱羧氰化反应 — 获得多取代的 β-酮腈 —

  摘要：

  开发了一种路易斯酸催化的环烯醇碳酸酯与氰化试剂的脱羧取代反应，以良好的收率得到β-酮腈。建议该反应通过氧烯丙基阳离子中间体或其等价物进行。有趣的是，氰化选择性地发生在中间体的受阻位点上，得到了多取代的β-酮腈。这种区域选择性是通过多种底物的氰化观察到的，并根据反应机理进行了讨论。

  DOI：

  10.1246/cl.220017

文献信息

• COMPOUNDS, COMPOSITIONS, AND MEZHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN MISFOLDING
  申请人：[en]WAVEBREAK THERAPEUTICS LIMITED

  公开号：WO2024129881A1

  公开（公告）日：2024-06-20

  The present disclosure provides compounds of formulae (I) and (II) useful for treating or lessening the severity of diseases or conditions, including those associated with alpha-synuclein protein.
• Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-<i>N</i>-acetylhexosaminidase Activity
  作者：Michael B. Tropak、Jianmin Zhang、Sayuri Yonekawa、Brigitte A. Rigat、Virender S. Aulakh、Matthew R. Smith、Hee-Jong Hwang、Marco A. Ciufolini、Don J. Mahuran

  DOI：10.1021/jm5017895

  日期：2015.6.11

  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.
• Lewis Acid-catalyzed Decarboxylative Cyanation of Cyclic Enol Carbonates — Access to Multi-substituted <i>β</i>-Ketonitriles —
  作者：Haruki Yokoyama、Yoichi Dokai、Natsuki Kimaru、Kodai Saito、Tohru Yamada

  DOI：10.1246/cl.220017

  日期：2022.4.5

  A Lewis acid-catalyzed decarboxylative substitution reaction of cyclic enol carbonates with a cyanation reagent was developed to give β-ketonitriles in good yield. It is proposed that the reaction proceeds through an oxyallyl cation intermediate or its equivalent. Interestingly, cyanation selectively took place at the more hindered site of the intermediate to afford a multi-substituted β-ketonitrile

  开发了一种路易斯酸催化的环烯醇碳酸酯与氰化试剂的脱羧取代反应，以良好的收率得到β-酮腈。建议该反应通过氧烯丙基阳离子中间体或其等价物进行。有趣的是，氰化选择性地发生在中间体的受阻位点上，得到了多取代的β-酮腈。这种区域选择性是通过多种底物的氰化观察到的，并根据反应机理进行了讨论。