4-ethyl-6-chloro-5-(4-chloro-phenyl)-pyrimidin-2-ylamine | 55694-06-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-ethyl-6-chloro-5-(4-chloro-phenyl)-pyrimidin-2-ylamine
• 英文别名: 4-Aethyl-6-chlor-5-(4-chlor-phenyl)-pyrimidin-2-ylamin；4-Chloro-5-(4-chlorophenyl)-6-ethylpyrimidin-2-amine
• CAS: 55694-06-9
• 化学式: C₁₂H₁₁Cl₂N₃
• 分子量: 268.145
• InChiKey: NCBKXYRDZOQBRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-ethyl-6-chloro-5-(4-chloro-phenyl)-pyrimidin-2-ylamine 在 palladium on activated charcoal 、 氢气 作用下， 生成 2-amino-4-ethyl-5-(4-chlorophenyl)pyrimidine
  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：

  乙胺嘧啶 在 盐酸 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 48.0h， 生成 4-ethyl-6-chloro-5-(4-chloro-phenyl)-pyrimidin-2-ylamine
  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

• US2680740
  申请人：——

  公开号：——

  公开（公告）日：——
• US2833767
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• DE899656
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  公开（公告）日：——
• US2680740A
  申请人：——

  公开号：——

  公开（公告）日：——
• US3947441A
  申请人：——

  公开号：US3947441A

  公开（公告）日：1976-03-30