2,4-diamino-5-{4-chloro-3-[N-(benzyl)amino]phenyl}-6-ethylpyrimidine | 500313-08-6

• 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-diamino-5-{4-chloro-3-[N-(benzyl)amino]phenyl}-6-ethylpyrimidine
• 英文别名: 5-(3-(Benzylamino)-4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine；5-[3-(benzylamino)-4-chlorophenyl]-6-ethylpyrimidine-2,4-diamine
• CAS: 500313-08-6
• 化学式: C₁₉H₂₀ClN₅
• 分子量: 353.854
• InChiKey: BVKFLVOOLWYWLR-UHFFFAOYSA-N

物化性质

• 沸点：
  619.0±65.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 2,4-diamino-5-{4-chloro-3-[N-(benzyl)amino]phenyl}-6-ethylpyrimidine 在 盐酸 、 sodium cyanoborohydride 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以90%的产率得到2,4-diamino-5-{3-[N-(benzyl)-N-methylamino]-4-chlorophenyl}-6-ethylpyrimidine
  参考文献：
  名称：

  Structural Studies on Bioactive Compounds. Part 36: Design, Synthesis and Biological Evaluation of Pyrimethamine-Based Antifolates Against Pneumocystis carinii

  摘要：

  As part of a research effort to improve the quality of current chemotherapy of Pneumocystis carinii pneumonia. we report a structure-based design project to optimise activity, species selectivity and pharmaceutical properties of the triazenyl-pyrimethamine TAB (4) (IC50 = 0.17 muM: rat liver DHFR IC50/P, carinii DHFR IC50 114). This has led us to design, synthesise and evaluate four new series of pyrimethamine derivatives bearing triazole, triazolium, triazinium and amino moieties at the 3'-position of the p-chloroplienyl ring. Such stabilised 'triazene' derivatives address the potentially compromised pharmaceutical profile of TAB and the 3'-amine substituted agents afford conformationally flexible substitutes. The benzylamino-pyrimethamine derivative (24a) (IC50 = 0.12 muM, rat liver DHFR IC50/P. Carinii DHFR IC50: 5.26) was the most potent and the only P. varinii-selective antifolate of the new series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00128-1
• 作为产物：
  描述：

  氯化苄 、 5-(3-氨基-4-氯-苯基)-6-乙基-嘧啶-2,4-二胺 以 乙醇 为溶剂， 反应 24.0h， 以59%的产率得到2,4-diamino-5-{4-chloro-3-[N-(benzyl)amino]phenyl}-6-ethylpyrimidine
  参考文献：
  名称：

  Structural Studies on Bioactive Compounds. Part 36: Design, Synthesis and Biological Evaluation of Pyrimethamine-Based Antifolates Against Pneumocystis carinii

  摘要：

  As part of a research effort to improve the quality of current chemotherapy of Pneumocystis carinii pneumonia. we report a structure-based design project to optimise activity, species selectivity and pharmaceutical properties of the triazenyl-pyrimethamine TAB (4) (IC50 = 0.17 muM: rat liver DHFR IC50/P, carinii DHFR IC50 114). This has led us to design, synthesise and evaluate four new series of pyrimethamine derivatives bearing triazole, triazolium, triazinium and amino moieties at the 3'-position of the p-chloroplienyl ring. Such stabilised 'triazene' derivatives address the potentially compromised pharmaceutical profile of TAB and the 3'-amine substituted agents afford conformationally flexible substitutes. The benzylamino-pyrimethamine derivative (24a) (IC50 = 0.12 muM, rat liver DHFR IC50/P. Carinii DHFR IC50: 5.26) was the most potent and the only P. varinii-selective antifolate of the new series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00128-1

文献信息

• Structural Studies on Bioactive Compounds. Part 36: Design, Synthesis and Biological Evaluation of Pyrimethamine-Based Antifolates Against Pneumocystis carinii
  作者：David C.M. Chan、Charles A. Laughton、Sherry F. Queener、Malcolm F.G. Stevens

  DOI：10.1016/s0968-0896(02)00128-1

  日期：2002.9

  As part of a research effort to improve the quality of current chemotherapy of Pneumocystis carinii pneumonia. we report a structure-based design project to optimise activity, species selectivity and pharmaceutical properties of the triazenyl-pyrimethamine TAB (4) (IC50 = 0.17 muM: rat liver DHFR IC50/P, carinii DHFR IC50 114). This has led us to design, synthesise and evaluate four new series of pyrimethamine derivatives bearing triazole, triazolium, triazinium and amino moieties at the 3'-position of the p-chloroplienyl ring. Such stabilised 'triazene' derivatives address the potentially compromised pharmaceutical profile of TAB and the 3'-amine substituted agents afford conformationally flexible substitutes. The benzylamino-pyrimethamine derivative (24a) (IC50 = 0.12 muM, rat liver DHFR IC50/P. Carinii DHFR IC50: 5.26) was the most potent and the only P. varinii-selective antifolate of the new series. (C) 2002 Elsevier Science Ltd. All rights reserved.