2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one | 889658-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
• 英文别名: 6-(2-Fluoro-6-chlorobenzyl)-2-thiouracil；6-[(2-chloro-6-fluorophenyl)methyl]-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 889658-62-2
• 化学式: C₁₁H₈ClFN₂OS
• 分子量: 270.715
• InChiKey: DYOSFMUFUOAPRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one 在 双氧水 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 7.0h， 生成 6-(2-fluoro-6-chlorobenzyl)pyrimidin-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthesis of new derivatives of 5-alkyl-6-(2,6-dihalobenzyl)-2-(methylsulfanyl)pyrimidin-4(3H)-one and the features of their oxidation

  摘要：

  The synthesis and features of the regioselective S-monomethylation of new 5-alkyl-6-(arylmethyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones were investigated, and also the character of the oxidative degradation of these compounds when treated with the system H2O2-AcOH.

  DOI：

  10.1134/s1070428010110151
• 作为产物：
  描述：

  2-(2-Chloro-6-fluorophenyl)-1-imidazol-1-ylethanone 在 sodium 、 三乙胺 、 magnesium chloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 2.25h， 生成 2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  Exploring the Role of 2-Chloro-6-fluoro Substitution in 2-Alkylthio-6-benzyl-5-alkylpyrimidin-4(3H)-ones: Effects in HIV-1-Infected Cells and in HIV-1 Reverse Transcriptase Enzymes

  摘要：

  A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.

  DOI：

  10.1021/jm500284x

文献信息

• 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3<i>H</i>)-ones, a Series of Anti-HIV-1 Agents of the Dihydro-alkoxy-benzyl-oxopyrimidine Family with Peculiar Structure−Activity Relationship Profile
  作者：Maxim B. Nawrozkij、Dante Rotili、Domenico Tarantino、Giorgia Botta、Alexandre S. Eremiychuk、Ira Musmuca、Rino Ragno、Alberta Samuele、Samantha Zanoli、Mercedes Armand-Ugón、Imma Clotet-Codina、Ivan A. Novakov、Boris S. Orlinson、Giovanni Maga、José A. Esté、Marino Artico、Antonello Mai

  DOI：10.1021/jm800340w

  日期：2008.8.1

  A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl-S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L1001 mutated RTs) assays, compounds carrying an ethylliso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.
• The specific character of the reaction of derivatives of 2-thioxo-2,3-dihydropyrimidin-4(1H)-one with iodomethane and alkyl chloromethyl sulfides
  作者：I. A. Novakov、B. S. Orlinson、M. B. Nawrozkij、A. Mai、M. Artico、D. Rotili、A. S. Eremiychuk、E. A. Gordeeva、L. L. Brunilina、J. A. Este

  DOI：10.1007/s10593-010-0492-3

  日期：2010.6

  The alkylation of 5-alkyl-6-(2,6-dihalobenzyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones with MeI, AllSCH(2)Cl, and MeSCH(2)Cl in the K(2)CO(3)-DMF, NaOMe-MeOH, and KOH-EtOH systems was investigated. A hypothetical mechanism for the reaction is examined, and an explanation is proposed for the composition of the reaction products. The presence of high anti-HIV-1 activity was established in the obtained derivatives of 2-[(allylsulfanyl)methyl]sulfanyl}pyrimidin-4(3H)-one.