4-[(2,6-difluorophenyl)methyl]-2-thiomorpholino-1H-pyrimidin-6-one

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-[(2,6-difluorophenyl)methyl]-2-thiomorpholino-1H-pyrimidin-6-one
• 英文别名: 4-[(2,6-difluorophenyl)methyl]-2-thiomorpholin-4-yl-1H-pyrimidin-6-one
• 化学式: C₁₅H₁₅F₂N₃OS
• 分子量: 323.366
• InChiKey: FDKFHSDBIIBHOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  硫代吗啉 、 6-(2,6-difluorophenylmethyl)-3,4-dihydro-2-methylthiopyrimidin-4(3H)-one 以57%的产率得到4-[(2,6-difluorophenyl)methyl]-2-thiomorpholino-1H-pyrimidin-6-one
  参考文献：
  名称：

  Synthesis and Biological Properties of Novel 2-Aminopyrimidin-4(3H)-ones Highly Potent against HIV-1 Mutant Strains

  摘要：

  Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a NN-disubstituted amino group or a cyclic amine at the pyrimidine-C, position, a hydrogen atom or a small alkyl group at C-5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C-6 position (F,NN-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV- I RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.

  DOI：

  10.1021/jm070811e