6-(2,6-difluorophenylmethyl)-3,4-dihydro-5-ethyl-2-thioxopyrimidin-4(3H)-one | 293300-24-0

• 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: 6-(2,6-difluorophenylmethyl)-3,4-dihydro-5-ethyl-2-thioxopyrimidin-4(3H)-one
• 英文别名: 6-(2,6-difluorobenzyl)-5-ethyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one；6-[(2,6-difluorophenyl)methyl]-5-ethyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 293300-24-0
• 化学式: C₁₃H₁₂F₂N₂OS
• 分子量: 282.314
• InChiKey: IFQDDDAUCFDLTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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：
  4

反应信息

• 作为反应物：
  描述：

  4'-甲氧基乙酰苯胺 、 6-(2,6-difluorophenylmethyl)-3,4-dihydro-5-ethyl-2-thioxopyrimidin-4(3H)-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-[(4-methoxyphenylamino)carbonylmethylthio]-6-(2,6-difluorobenzyl)-5-ethylpyrimidin-4(3H)-one
  参考文献：
  名称：

  发现二氢-烷氧基-苄基-氧嘧啶作为有前途的抗流感病毒剂

  摘要：

  合成了一系列新颖的二氢-烷氧基-苄基-氧嘧啶衍生物，并评估了它们在Madin-Darby犬肾细胞中对流感病毒的活性。四个二氢-烷氧基苄基oxopyrimidine衍生物（4A1，4A2，4A3，和4D1）显示对流感病毒有效的活性。其中，化合物4A3与抗流感A宽的活性最有前途的引线（抗病毒EC 50倍的图9和18的值 μ米分别用于A / H1N1和A / H3N2亚型）和B型流感病毒（EC 50：33  μ米）。这些二氢-烷氧基-苄基-氧嘧啶衍生物的抗病毒作用机制必须与目前批准的针对病毒M2或神经氨酸酶蛋白的抗流感病毒药物完全不同。二氢烷氧基苄基氧嘧啶衍生物代表了进一步优化和开发新型抗流感病毒剂的新途径。

  DOI：

  10.1111/j.1747-0285.2011.01180.x
• 作为产物：
  描述：

  2-(2,6-Difluoro-phenyl)-1-imidazol-1-yl-ethanone 在 sodium ethanolate 、 三乙胺 、 magnesium chloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 5.25h， 生成 6-(2,6-difluorophenylmethyl)-3,4-dihydro-5-ethyl-2-thioxopyrimidin-4(3H)-one
  参考文献：
  名称：

  Sbardella, Gianluca; Mai, Antonello; Artico, Marino, Medicinal Chemistry Research, 2000, vol. 10, # 1, p. 30 - 39

  摘要：

  DOI：

文献信息

• PYRIMIDINONE-CONTAINING COMPOUND, PREPARATION METHOD THEREOF, PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
  申请人：YUNNAN UNIVERSITY

  公开号：US20200399248A1

  公开（公告）日：2020-12-24

  Disclosed is a pyrimidinone-containing compound represented by formula I, a preparation method thereof, a pharmaceutical composition, and an application thereof. The pyrimidinone-containing compound of the present disclosure can be used as HIV-1 inhibitor and can be also used in the treatment of human immunodeficiency virus infection.

  本公开揭示了一种含有嘧啶酮基团的化合物，其化学式如下（I），以及其制备方法、药物组合物和应用。本公开的含有嘧啶酮基团的化合物可用作HIV-1抑制剂，也可用于治疗人类免疫缺陷病毒感染。
• 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
• Dihydro-alkylthio-benzyl-oxopyrimidines as Inhibitors of Reverse Transcriptase: Synthesis and Rationalization of the Biological Data on Both Wild-Type Enzyme and Relevant Clinical Mutants
  作者：Claudia Mugnaini、Maddalena Alongi、Andrea Togninelli、Harsukh Gevariya、Antonella Brizzi、Fabrizio Manetti、Cesare Bernardini、Lucilla Angeli、Andrea Tafi、Luca Bellucci、Federico Corelli、Silvio Massa、Giovanni Maga、Alberta Samuele、Marcella Facchini、Imma Clotet-Codina、Mercedes Armand-Ugón、José A. Esté、Maurizio Botta

  DOI：10.1021/jm0708230

  日期：2007.12.27

  A series of novel S-DABO analogues, characterized by different substitution patterns at positions 2, 5, and 6 of the heterocyclic ring, were synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Most of the compounds proved to be highly active on the wild-type enzyme both in enzymatic and cellular assays, with one of them emerging as the most active reverse transcriptase inhibitor reported so far (EC50wt = 25 pM). The general loss of potency displayed by the compounds toward clinically relevant mutant strains was deeply studied through a molecular modeling approach, leading to the evidence that the dynamic of the entrance in the non-nucleoside binding pocket could represent the basis of the inhibitory activity of the molecules.
• 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.