(S)-2-(4-(3-(2,4-diamino-6-hydroxypyrimidin-5-yl)ureido)benzamido)hexanedioic acid

• 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: (S)-2-(4-(3-(2,4-diamino-6-hydroxypyrimidin-5-yl)ureido)benzamido)hexanedioic acid
• 英文别名: (2S)-2-[[4-[(2,4-diamino-6-oxo-1H-pyrimidin-5-yl)carbamoylamino]benzoyl]amino]hexanedioic acid
• 化学式: C₁₈H₂₁N₇O₇
• 分子量: 447.407
• InChiKey: BCFRGOQGMKXYKO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  238
• 氢给体数：
  8
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  乙基-4-异叠酸苯酯 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.5h， 生成 (S)-2-(4-(3-(2,4-diamino-6-hydroxypyrimidin-5-yl)ureido)benzamido)hexanedioic acid
  参考文献：
  名称：

  Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of Trypanosoma brucei FolD and Testing for Antiparasitic Activity

  摘要：

  The bifunctional enzyme N-5,N-10-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (Poll)) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 mu M, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 mu M). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP(+). and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors.

  DOI：

  10.1021/acs.jmedchem.5b00687

文献信息

• Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of <i>Trypanosoma brucei</i> FolD and Testing for Antiparasitic Activity
  作者：Thomas C. Eadsforth、Andrea Pinto、Rosaria Luciani、Lucia Tamborini、Gregorio Cullia、Carlo De Micheli、Luciana Marinelli、Sandro Cosconati、Ettore Novellino、Leonardo Lo Presti、Anabela Cordeiro da Silva、Paola Conti、William N. Hunter、Maria P. Costi

  DOI：10.1021/acs.jmedchem.5b00687

  日期：2015.10.22

  The bifunctional enzyme N-5,N-10-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (Poll)) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 mu M, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 mu M). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP(+). and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors.