3-氧代-4-(2-氟-6-氯苯基)-2-乙基丁酸乙酯 | 1044749-10-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氧代-4-(2-氟-6-氯苯基)-2-乙基丁酸乙酯
• 英文名称: ethyl 3-oxo-4-(2-fluoro-6-chlorophenyl)-2-ethylbutanoate
• 英文别名: Ethyl 3-oxo-4-(2-fluoro-6-chlorophenyl)-2-ethyl-butanoate；ethyl 4-(2-chloro-6-fluorophenyl)-2-ethyl-3-oxobutanoate
• CAS: 1044749-10-1
• 化学式: C₁₄H₁₆ClFO₃
• mdl: MFCD18055223
• 分子量: 286.731
• InChiKey: RDEXYJMNJYROHI-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：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氧代-4-(2-氟-6-氯苯基)-2-乙基丁酸乙酯 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-[(4-bromophenylamino)carbonylmethylthio]-6-(2-chloro-6-fluorobenzyl)-5-ethylpyrimidin-4(3H)-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
• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 以 甲苯 为溶剂， 反应 2.5h， 生成 3-氧代-4-(2-氟-6-氯苯基)-2-乙基丁酸乙酯
  参考文献：
  名称：

  5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a Series of Anti-HIV-1 Agents of the Dihydro-alkoxy-benzyl-oxopyrimidine Family with Peculiar Structure−Activity Relationship Profile

  摘要：

  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.

  DOI：

  10.1021/jm800340w

文献信息

• 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.
• 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 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