5-ethyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one | 1044749-15-6

• 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-ethyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
• 英文别名: 6-(6-chloro-2-fluorobenzyl)-5-ethyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one；6-[(2-chloro-6-fluorophenyl)methyl]-5-ethyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 1044749-15-6
• 化学式: C₁₃H₁₂ClFN₂OS
• 分子量: 298.768
• InChiKey: OWZYNOLGFIZYOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 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-ethyl-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， 生成 6-(6-chloro-2-fluorobenzyl)-5-ethylpyrimidine-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-氯-6-氟苯乙睛 在 sodium ethanolate 、 锌 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.75h， 生成 5-ethyl-2-thioxo-6-(2-fluoro-6-chlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  6取代的5-烷基-2-（苯氨基羰基甲硫基）嘧啶-4（3H）-ones作为强效HIV-1 NNRTI的合成及生物学评价

  摘要：

  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

  DOI：

  10.1002/cmdc.201000555

文献信息

• 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。
• 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.