2,4-diamino-5-[4-chloro-3-(3-ethyl-3-methyltriazen-1-yl)phenyl]-6-ethylpyrimidine

• 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: 2,4-diamino-5-[4-chloro-3-(3-ethyl-3-methyltriazen-1-yl)phenyl]-6-ethylpyrimidine
• 化学式: C₁₅H₂₀ClN₇
• 分子量: 333.824
• InChiKey: METLTCJCYLJORR-QURGRASLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  105.78
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  N-乙基甲基胺 、 在 sodium carbonate 作用下， 以 水 为溶剂， 反应 2.0h， 生成 2,4-diamino-5-[4-chloro-3-(3-ethyl-3-methyltriazen-1-yl)phenyl]-6-ethylpyrimidine
  参考文献：
  名称：

  Structural Studies on Bioactive Compounds. 28. Selective Activity of Triazenyl-Substituted Pyrimethamine Derivatives against Pneumocystis carinii Dihydrofolate Reductase

  摘要：

  Triazenyl-substituted pyrimethamine derivatives 10a-s have been prepared by coupling diazotized 2,4-diamino-5-(3-amino-4-chlorophenyl)6-ethyl pyrimidine (1c) with a series of secondary amines in aqueous sodium carbonate solution. The triazenes which are stable and poorly soluble as free bases form more soluble, but unstable, salts with alkanesulfonic acids. The lead dimethyltriazene 2,4-diamino-5-[4-chloro-3-(3,3-dimethyltriazen-1-yl)phenyl]-6- ethylpyrimidine (4a) forms a crystalline ethanesulfonic acid salt (solvated with 2-propanol), which is protonated at the pyrimidine N-1 position as determined by X-ray crystallography. The ability of these new triazenes to inhibit Pneumocystis carinii dihydrofolate reductase in vitro has been compared to that of triazene 4a. The most potent and selective compound, 2,5-diamino-5-[3-[3-[2-(acetyloxy)ethyl]-3-benzyltriazen-1-yl]- 4-chlorophenyl]-6-ethylpyrimidine (14a), has an IC50 value of 0.17 mu M against the microbial enzyme and potentially useful selectivity (rat liver IC50/P. carinii IC50 = 114).

  DOI：

  10.1021/jm970050n

文献信息

• Structural Studies on Bioactive Compounds. 28. Selective Activity of Triazenyl-Substituted Pyrimethamine Derivatives against <i>Pneumocystis </i><i>carinii </i>Dihydrofolate Reductase
  作者：Malcolm F. G. Stevens、Keith S. Phillip、Daniel L. Rathbone、Dennis M. O'Shea、Sherry F. Queener、Carl H. Schwalbe、Peter A. Lambert

  DOI：10.1021/jm970050n

  日期：1997.6.1

  Triazenyl-substituted pyrimethamine derivatives 10a-s have been prepared by coupling diazotized 2,4-diamino-5-(3-amino-4-chlorophenyl)6-ethyl pyrimidine (1c) with a series of secondary amines in aqueous sodium carbonate solution. The triazenes which are stable and poorly soluble as free bases form more soluble, but unstable, salts with alkanesulfonic acids. The lead dimethyltriazene 2,4-diamino-5-[4-chloro-3-(3,3-dimethyltriazen-1-yl)phenyl]-6- ethylpyrimidine (4a) forms a crystalline ethanesulfonic acid salt (solvated with 2-propanol), which is protonated at the pyrimidine N-1 position as determined by X-ray crystallography. The ability of these new triazenes to inhibit Pneumocystis carinii dihydrofolate reductase in vitro has been compared to that of triazene 4a. The most potent and selective compound, 2,5-diamino-5-[3-[3-[2-(acetyloxy)ethyl]-3-benzyltriazen-1-yl]- 4-chlorophenyl]-6-ethylpyrimidine (14a), has an IC50 value of 0.17 mu M against the microbial enzyme and potentially useful selectivity (rat liver IC50/P. carinii IC50 = 114).