2-(cyclopentylthio)-6-(1-(2,6-difluorophenyl)propyl)-5-methylpyrimidin-4(3H)-one | 1320339-97-6

• 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: 2-(cyclopentylthio)-6-(1-(2,6-difluorophenyl)propyl)-5-methylpyrimidin-4(3H)-one
• 英文别名: 2-cyclopentylsulfanyl-4-[1-(2,6-difluorophenyl)propyl]-5-methyl-1H-pyrimidin-6-one
• CAS: 1320339-97-6
• 化学式: C₁₉H₂₂F₂N₂OS
• 分子量: 364.459
• InChiKey: KSMUQSCQHJHTDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二氟苯乙酸 在 正丁基锂 、 sodium 、 potassium carbonate 、 三乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 2-(cyclopentylthio)-6-(1-(2,6-difluorophenyl)propyl)-5-methylpyrimidin-4(3H)-one
  参考文献：
  名称：

  Modulation of Cell Differentiation, Proliferation, and Tumor Growth by Dihydrobenzyloxopyrimidine Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4-dihydropyrimidin-4(3H)-one derivatives (3a-h) belonging to the F-2-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cells. Among tested compounds, the most potent is 3g (SPV122), which also induces apoptosis in a cell-density-dependent manner and antagonizes tumor growth in animal models. All these effects are similar or even more pronounced than those previously reported for other nucleoside or non-nucleoside inhibitors of reverse transcriptase or by functional knockout of the reverse-transcriptase-encoding long interspersed element 1 by RNA interference (RNAi). Taken together with our previously reported results, these data further confirm our idea that cellular alterations induced by NNRTIs are a consequence of the inhibition of the endogenous reverse transcriptase in A375 cells and support the potential of NNRTIs as valuable agents in cancer therapy.

  DOI：

  10.1021/jm200734j

文献信息

• Modulation of Cell Differentiation, Proliferation, and Tumor Growth by Dihydrobenzyloxopyrimidine Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Gianluca Sbardella、Antonello Mai、Sara Bartolini、Sabrina Castellano、Roberto Cirilli、Dante Rotili、Ciro Milite、Marisabella Santoriello、Serena Orlando、Ilaria Sciamanna、Annalucia Serafino、Patrizia Lavia、Corrado Spadafora

  DOI：10.1021/jm200734j

  日期：2011.8.25

  A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4-dihydropyrimidin-4(3H)-one derivatives (3a-h) belonging to the F-2-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cells. Among tested compounds, the most potent is 3g (SPV122), which also induces apoptosis in a cell-density-dependent manner and antagonizes tumor growth in animal models. All these effects are similar or even more pronounced than those previously reported for other nucleoside or non-nucleoside inhibitors of reverse transcriptase or by functional knockout of the reverse-transcriptase-encoding long interspersed element 1 by RNA interference (RNAi). Taken together with our previously reported results, these data further confirm our idea that cellular alterations induced by NNRTIs are a consequence of the inhibition of the endogenous reverse transcriptase in A375 cells and support the potential of NNRTIs as valuable agents in cancer therapy.