2-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-4(3H)-one | 91396-20-2

• 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: 2-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-4(3H)-one
• 英文别名: 2-amino-6-ethyl-5-(4-chlorophenyl)pyrimidin-4(3H)-one；2-amino-5-(4-chloro-phenyl)-6-ethyl-3H-pyrimidin-4-one；6-ethyl-2-amino-5-(4-chloro-phenyl)-3H-pyrimidin-4-one；6-Aethyl-2-amino-5-(4-chlor-phenyl)-3H-pyrimidin-4-on；4(1H)-Pyrimidinone, 2-amino-5-(4-chlorophenyl)-6-ethyl-；2-amino-5-(4-chlorophenyl)-4-ethyl-1H-pyrimidin-6-one
• CAS: 91396-20-2
• 化学式: C₁₂H₁₂ClN₃O
• 分子量: 249.7
• InChiKey: KTEOTBKBKDEYDF-UHFFFAOYSA-N

物化性质

• 沸点：
  411.9±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 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：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-4(3H)-one 在 三氯氧磷 作用下， 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
• 作为产物：
  描述：

  乙胺嘧啶 在 盐酸 、 水 作用下， 生成 2-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-4(3H)-one
  参考文献：
  名称：

  Hitchings et al., Journal of the Chemical Society, 1956, p. 1019,1023, 1024

  摘要：

  DOI：

文献信息

• Structural studies on bio-active compounds. Part 3. Re-examination of the hydrolysis of the antimalarial drug pyrimethamine and related derivatives and crystal structure of a hydrolysis product
  作者：Roger J. Griffin、Carl H. Schwalbe、Malcolm F. G. Stevens、Kait P. Wong

  DOI：10.1039/p19850002267

  日期：——

  Hydrolysis of the diaminopyrimidine pyrimethamine and some of its 5-(3′-substituted)phenyl derivatives with 6M-hydrochloric acid, or deamination with nitrous acid, affords mixtures of isomeric aminopyrimidinones. The ratio of products is influenced by the nature of the substituent in the phenyl ring.

  用6 M-盐酸水解二氨基嘧啶嘧啶胺及其某些5-（3'-取代）苯基衍生物，或用亚硝酸脱氨基，得到异构的氨基嘧啶酮混合物。产物的比例受苯环中取代基的性质影响。
• US2680740
  申请人：——

  公开号：——

  公开（公告）日：——
• US2680740A
  申请人：——

  公开号：——

  公开（公告）日：——
• TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS WITH PYRIMETHAMINE AND ANALOGUES
  申请人：Alsgen, Inc.

  公开号：EP1917017B1

  公开（公告）日：2010-02-03
• [EN] MODULATION OF NEURODEGENERATIVE DISEASES<br/>[FR] MODULATION DE MALADIES NEURODEGENERATIVES
  申请人：ALSGEN LLC

  公开号：WO2006096405A2

  公开（公告）日：2006-09-14

  (EN) Methods and compositions are disclosed for selectively interfering with protein synthesis in a central nervous system, meningial, or muscle cell by administrating a pharmacological agent. In particular, methods and compositions that interfere with SOD-I protein synthesis are disclosed.(FR) L'invention porte sur des compositions et sur des méthodes visant à entraver sélectivement la synthèse des protéines dans le système nerveux central, les méninges ou les cellules des muscles, ce procédé consistant à administrer un agent pharmacologique. L'invention porte notamment sur des compositions et sur des méthodes qui entravent la synthèse de la protéine SOD-1.