5-methyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one | 1044749-14-5

• 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: 5-methyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
• 英文别名: 6-(2-Fluoro-6-chlorobenzyl)-2-thiothymine；6-[(2-chloro-6-fluorophenyl)methyl]-5-methyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 1044749-14-5
• 化学式: C₁₂H₁₀ClFN₂OS
• 分子量: 284.742
• InChiKey: FBHCOVILCFWFMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  5-methyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 6-benzyl-5-methyl-2-[(3-phenylpropyl)amino]pyrimidin-4(3H)-one
  参考文献：
  名称：

  高效固相合成异胞嘧啶衍生物

  摘要：

  我们已经研究了将相应的2-硫代胸腺嘧啶固定在Merrifield树脂上，将固定化形式氧化为砜，基于固相合成新型6-（芳基甲基）-5-甲基-异胞嘧啶衍生物的潜在用途，以及在温和条件下后者的氨解作用。

  DOI：

  10.1007/s10593-010-0434-0
• 作为产物：
  描述：

  2-{[(allylsulfanyl)methyl]sulfanyl}-6-(6-chloro-2-fluorobenzyl)-5-methylpyrimidin-4(3H)-one 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 5-methyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  The specific character of the reaction of derivatives of 2-thioxo-2,3-dihydropyrimidin-4(1H)-one with iodomethane and alkyl chloromethyl sulfides

  摘要：

  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.

  DOI：

  10.1007/s10593-010-0492-3

文献信息

• Synthesis and Biological Evaluation of 6-Substituted 5-Alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as Potent HIV-1 NNRTIs
  作者：Mingyan Yu、Zhenyu Li、Shuai Liu、Erkang Fan、Christophe Pannecouque、Erik De Clercq、Xinyong Liu

  DOI：10.1002/cmdc.201000555

  日期：2011.5.2

  A series of new 5‐alkyl‐2‐phenylaminocarbonylmethylthiopyrimidin‐4(3H)‐ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti‐HIV activity in MT‐4 cells. Most of these new congeners exhibited moderate to good activities against the wild‐type virus, with EC50 values in the range of 1.40–0.19 μM. Among them, 2‐[(4‐cyan

  合成了一系列新的5-烷基-2-苯基氨基羰基甲基硫嘧啶-4（3 H）-在嘧啶环的C6位带有不同取代的芳基甲基的部分，并评估了其在MT-4细胞中的抗HIV活性。大多数这些新的同系物表现出中度到对野生型病毒的创先争优活动，与EC 50个在1.40-0.19μ的范围值中号。其中2-[（（4-氰基苯基氨基）羰基甲硫基] -6-（2-氯-6-氟苄基）-5-乙基嘧啶-4（3 H）-一4 b6是被赋予最高的宽泛度的化合物之一。光谱HIV-1的抑制活性，以EC 50个为0.19±0.005μ值中号对野生型病毒，1.05±0.24μ中号（双重抵抗）的E138K应变，和2.38±0.13μ中号（4.5倍的抗性）压靠在Y181C菌株。此外，使用选定的衍生物进行了针对野生型HIV-1 RT的逆转录酶（RT）抑制试验，证实了这些化合物的主要靶标是HIV-1 RT，并且这些新的S -DABO类似物充当了非核苷RT。抑制
• Experimental and quantum chemical study of the reactions of 2-methyloxirane with 5-alkyl-6-(2,6-dihalobenzyl)-2-thioxo1,2-dihydropyrimidine-4(3H)-one derivatives
  作者：A. S. Yablokov、D. V. Steglenko、E. A. Ruchko、M. B. Nawrozkij、L. L. Brunilina、I. A. Novakov、V. I. Minkin

  DOI：10.1007/s11172-015-0896-4

  日期：2015.3

  The reactions of 5-alkyl-6-(2,6-dihalobenzyl)-2-thioxo-1,2-dihydropyrimidin-4(3H)-one with 2-methyloxirane in an alkaline medium afforded uracil and 2-[(2-hydroxyprop-1yl)sulfanyl]pyrimidin-4(3H)-one derivatives. The mechanism proposed for these transformations was studied using the DFT/B3LYP/311+G** quantum chemical method, and the influence of the Nathan—Baker effect on the chemical nature and composition of the reaction products was shown.

  在碱性介质中，5-烷基-6-(2,6-二卤苄基)-2-硫酮-1,2-二氢嘧啶-4(3H)-酮与 2-甲基环氧乙烷反应生成了尿嘧啶和 2-[(2-羟基丙-1-基)硫]嘧啶-4(3H)-酮衍生物。利用 DFT/B3LYP/311+G** 量子化学方法对这些转化的机理进行了研究，并显示了 Nathan-Baker 效应对反应产物化学性质和组成的影响。
• Exploring the Role of 2-Chloro-6-fluoro Substitution in 2-Alkylthio-6-benzyl-5-alkylpyrimidin-4(3<i>H</i>)-ones: Effects in HIV-1-Infected Cells and in HIV-1 Reverse Transcriptase Enzymes
  作者：Dante Rotili、Domenico Tarantino、Maxim B. Nawrozkij、Alexandre S. Babushkin、Giorgia Botta、Biagina Marrocco、Roberto Cirilli、Sergio Menta、Roger Badia、Emmanuele Crespan、Flavio Ballante、Rino Ragno、José A. Esté、Giovanni Maga、Antonello Mai

  DOI：10.1021/jm500284x

  日期：2014.6.26

  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.
• 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.
• Synthesis of new derivatives of 5-alkyl-6-(2,6-dihalobenzyl)-2-(methylsulfanyl)pyrimidin-4(3H)-one and the features of their oxidation
  作者：I. A. Novakov、B. S. Orlinson、M. B. Navrotskii、A. S. Eremiichuk、L. L. Brunilina、E. A. Gordeeva、E. N. Gerasimov

  DOI：10.1134/s1070428010110151

  日期：2010.11

  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.