6-(2,6-dichloro-benzyl)-5-ethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one | 959635-19-9

• 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: 6-(2,6-dichloro-benzyl)-5-ethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one
• 英文别名: 5-ethyl-2-thioxo-6-(2,6-dichlorobenzyl)-2,3-dihydropyrimidin-4(1H)-one；5-Ethyl-2-thioxo-6-(2,6-dichlorobenzyl)-2,3-di-hydropyrimidin-4(1h)-one；6-[(2,6-dichlorophenyl)methyl]-5-ethyl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 959635-19-9
• 化学式: C₁₃H₁₂Cl₂N₂OS
• 分子量: 315.223
• InChiKey: SUBHBJZMLQIAFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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：
  2

反应信息

• 作为反应物：
  描述：

  6-(2,6-dichloro-benzyl)-5-ethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one 在 methyloxirane 、 sodium hydroxide 作用下， 以 水 为溶剂， 以86%的产率得到6-(2,6-dichlorobenzyl)-5-ethylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  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

  摘要：

  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。

  DOI：

  10.1007/s11172-015-0896-4
• 作为产物：
  描述：

  2,6-二氯苯乙酸 在 sodium ethanolate 、 N,N'-羰基二咪唑 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 6-(2,6-dichloro-benzyl)-5-ethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one
  参考文献：
  名称：

  C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity

  摘要：

  DOI：

  10.1016/j.bioorg.2021.105494

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。
• [EN] 2-THIOMETHYLPYRAZOLOPYRIMIDINONE COMPOUND, PREPARATION METHOD THEREOF, PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF<br/>[FR] COMPOSÉ DE 2-THIOMÉTHYLPYRAZOLOPYRIMIDINONE, PROCÉDÉ DE PRÉPARATION CORRESPONDANT, COMPOSITION PHARMACEUTIQUE ET UTILISATION ASSOCIÉES<br/>[ZH] 一种2-硫甲基吡唑嘧啶酮类化合物、其制备方法、药物组合物及应用
  申请人：UNIV YUNNAN

  公开号：WO2019170050A1

  公开（公告）日：2019-09-12

  本发明公开了一种2-硫甲基吡唑嘧啶酮类化合物、其制备方法、药物组合物及应用。本发明所述的2-硫甲基吡唑嘧啶酮类化合物的结构如式I所示，其中：A为S、O、NH或NCH3；R1为H、C1-C6的支链或直链烷基、或C3-C6环烷基；R2为H或卤素；R3为H、C1-C12的支链或直链烷基、C3-C6环烷基、C6-C20的芳基、C2-C10的杂芳基、被一个或多个R3a取代的C6-C20的芳基或被一个或多个R3b取代的C2-C10的杂芳基；α环为环己基或被n个相同或不同的R4取代的苯基，R4为卤素、羟基、氰基、硝基、氨基、C1-C6的支链或直链烷基、或C1-C6的支链或直链烷氧基。本发明所述的2-硫甲基吡唑嘧啶酮类化合物可作为HIV-1抑制剂并用于制备治疗和/或预防免疫缺陷病毒的药物。
• 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.
• 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.