2-amino-6-(2,6-difluorophenylmethyl)pyrimidin-4(3H)-one | 850075-94-4

• 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: 2-amino-6-(2,6-difluorophenylmethyl)pyrimidin-4(3H)-one
• 英文别名: 2-amino-4-[(2,6-difluorophenyl)methyl]-1H-pyrimidin-6-one
• CAS: 850075-94-4
• 化学式: C₁₁H₉F₂N₃O
• 分子量: 237.209
• InChiKey: PVWLXPCEKTWNIC-UHFFFAOYSA-N

物化性质

• 熔点：
  276.5-277 °C(Solv: ethanol (64-17-5))
• 沸点：
  373.7±52.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-6-(2,6-difluorophenylmethyl)pyrimidin-4(3H)-one 、 2,5-二甲氧基四氢呋喃 在 溶剂黄146 作用下， 反应 5.0h， 以43%的产率得到4-[(2,6-difluorophenyl)methyl]-2-pyrrol-1-yl-1H-pyrimidin-6-one
  参考文献：
  名称：

  Synthesis and Biological Properties of Novel 2-Aminopyrimidin-4(3H)-ones Highly Potent against HIV-1 Mutant Strains

  摘要：

  Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a NN-disubstituted amino group or a cyclic amine at the pyrimidine-C, position, a hydrogen atom or a small alkyl group at C-5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C-6 position (F,NN-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV- I RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.

  DOI：

  10.1021/jm070811e
• 作为产物：
  描述：

  胍 、 ethyl 4-(2,6-difluorophenyl)-3-oxobutanoate 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以78%的产率得到2-amino-6-(2,6-difluorophenylmethyl)pyrimidin-4(3H)-one
  参考文献：
  名称：

  5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family

  摘要：

  2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones (F-2-NH-DABOs) 4, 5 belonging to the dihydro-alkoxy-benzyl-oxopyrimidine (DABO) family and bearing different alkyl- and arylamino side chains at the C-2-position of the pyrimidine ring were designed as active against wild type (wt) human immunodeficiency virus type 1 (HIV-1) and some relevant HIV-1 mutants. Biological evaluation indicated the importance of the further anchor point of compounds 4, 5 into the nonnucleoside binding site (NNBS): newly synthesized compounds were highly active against both wild type and the Y181C HIV-1 strains. In anti-wt HIV-1 assay the potency of amino derivatives did not depend on the size or shape of the C-2-amino side chain, but it associated with the presence of one or two methyl groups (one at the pyrimidine C-5-position and the other at the benzylic carbon), being thymine, alpha-methyluracil or alpha-methylthymine derivatives almost equally active in reducing wt HIV-1-induced cytopathogenicity in MT-4 cells. Against the Y181C mutant strain, 2,6-difluorobenzyl-alpha-methylthymine derivatives 4d, 5h'-n' showed the highest potency and selectivity among tested compounds, both a properly sized C-2-NH side chain and the presence of two methyl groups (at C-5 and benzylic positions) being crucial for high antiviral action. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.005

文献信息

• Synthesis and Biological Properties of Novel 2-Aminopyrimidin-4(3<i>H</i>)-ones Highly Potent against HIV-1 Mutant Strains
  作者：Antonello Mai、Marino Artico、Dante Rotili、Domenico Tarantino、Imma Clotet-Codina、Mercedes Armand-Ugón、Rino Ragno、Silvia Simeoni、Gianluca Sbardella、Maxim B. Nawrozkij、Alberta Samuele、Giovanni Maga、José A. Esté

  DOI：10.1021/jm070811e

  日期：2007.11.1

  Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a NN-disubstituted amino group or a cyclic amine at the pyrimidine-C, position, a hydrogen atom or a small alkyl group at C-5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C-6 position (F,NN-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV- I RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.
• 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family
  作者：Antonello Mai、Marino Artico、Rino Ragno、Gianluca Sbardella、Silvio Massa、Chiara Musiu、Massimo Mura、Flavia Marturana、Alessandra Cadeddu、Giovanni Maga、Paolo La Colla

  DOI：10.1016/j.bmc.2005.01.005

  日期：2005.3

  2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones (F-2-NH-DABOs) 4, 5 belonging to the dihydro-alkoxy-benzyl-oxopyrimidine (DABO) family and bearing different alkyl- and arylamino side chains at the C-2-position of the pyrimidine ring were designed as active against wild type (wt) human immunodeficiency virus type 1 (HIV-1) and some relevant HIV-1 mutants. Biological evaluation indicated the importance of the further anchor point of compounds 4, 5 into the nonnucleoside binding site (NNBS): newly synthesized compounds were highly active against both wild type and the Y181C HIV-1 strains. In anti-wt HIV-1 assay the potency of amino derivatives did not depend on the size or shape of the C-2-amino side chain, but it associated with the presence of one or two methyl groups (one at the pyrimidine C-5-position and the other at the benzylic carbon), being thymine, alpha-methyluracil or alpha-methylthymine derivatives almost equally active in reducing wt HIV-1-induced cytopathogenicity in MT-4 cells. Against the Y181C mutant strain, 2,6-difluorobenzyl-alpha-methylthymine derivatives 4d, 5h'-n' showed the highest potency and selectivity among tested compounds, both a properly sized C-2-NH side chain and the presence of two methyl groups (at C-5 and benzylic positions) being crucial for high antiviral action. (c) 2005 Elsevier Ltd. All rights reserved.