2-chloro-N-((2-phenyl-4-thiazolyl)methyl)-4-pyrimidinamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-((2-phenyl-4-thiazolyl)methyl)-4-pyrimidinamine
• 英文别名: 2-chloro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]pyrimidin-4-amine
• 化学式: C₁₄H₁₁ClN₄S
• 分子量: 302.787
• InChiKey: ZQOSABLSPIPUQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N-((2-phenyl-4-thiazolyl)methyl)-4-pyrimidinamine 、 异丁胺 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 以81%的产率得到N²-isobutyl-N⁴-((2-phenyl-4-thiazolyl)methyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane

  摘要：

  As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N-2-isobutyl-N-4-((4-methyl-2-phenylthiazol-5-yl) methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)-methyl)N-2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coil and S. aureus growth at concentrations as low as 2 and 3 mu g/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112141
• 作为产物：
  描述：

  2-苯基噻唑-4-甲酸乙酯 在 lithium aluminium tetrahydride 、 三溴化磷 、 potassium phtalimide 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-chloro-N-((2-phenyl-4-thiazolyl)methyl)-4-pyrimidinamine
  参考文献：
  名称：

  Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane

  摘要：

  As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N-2-isobutyl-N-4-((4-methyl-2-phenylthiazol-5-yl) methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)-methyl)N-2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coil and S. aureus growth at concentrations as low as 2 and 3 mu g/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112141

文献信息

• Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane
  作者：Tingting Fan、Weikai Guo、Ting Shao、Wenbo Zhou、Pan Hu、Mingyao Liu、Yihua Chen、Zhengfang Yi

  DOI：10.1016/j.ejmech.2020.112141

  日期：2020.3

  As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N-2-isobutyl-N-4-((4-methyl-2-phenylthiazol-5-yl) methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)-methyl)N-2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coil and S. aureus growth at concentrations as low as 2 and 3 mu g/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria. (C) 2020 Elsevier Masson SAS. All rights reserved.