6-(2-morpholinopyrimidin-4-yl)-N-(pyrimidin-2-yl)quinazolin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(2-morpholinopyrimidin-4-yl)-N-(pyrimidin-2-yl)quinazolin-4-amine
• 英文别名: NEU-4436；6-(2-morpholin-4-ylpyrimidin-4-yl)-N-pyrimidin-2-ylquinazolin-4-amine
• 化学式: C₂₀H₁₈N₈O
• 分子量: 386.416
• InChiKey: GAOSROPPASDHQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(4-溴嘧啶-2-基)吗啉 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 caesium carbonate 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.25h， 生成 6-(2-morpholinopyrimidin-4-yl)-N-(pyrimidin-2-yl)quinazolin-4-amine
  参考文献：
  名称：

  Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation

  摘要：

  Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. We previously reported the discovery of 2 (NEU-617), a small molecule with activity against T brucei bloodstream proliferation. Further optimization of 2 to improve the physicochemical properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants 9i and 9j, and the linker variant 18. Although these 3 compounds had reduced potency compared to 2, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered 90 with potent activity towards T. brucei, T cruzi and L major, while four others compounds (17,18, 21, 26) showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.007

文献信息

• Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation
  作者：Jennifer L. Woodring、Kelly A. Bachovchin、Kimberly G. Brady、Mitchell F. Gallerstein、Jessey Erath、Scott Tanghe、Susan E. Leed、Ana Rodriguez、Kojo Mensa-Wilmot、Richard J. Sciotti、Michael P. Pollastri

  DOI：10.1016/j.ejmech.2017.10.007

  日期：2017.12

  Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. We previously reported the discovery of 2 (NEU-617), a small molecule with activity against T brucei bloodstream proliferation. Further optimization of 2 to improve the physicochemical properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants 9i and 9j, and the linker variant 18. Although these 3 compounds had reduced potency compared to 2, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered 90 with potent activity towards T. brucei, T cruzi and L major, while four others compounds (17,18, 21, 26) showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics. (C) 2017 Elsevier Masson SAS. All rights reserved.