6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyl-1-{[[4-(3-hydroxyprop-1-ynyl)benzyl]oxy]methyl}pyrimidine-2,4(1H,3H)-dione | 1612757-29-5

• 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-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyl-1-{[[4-(3-hydroxyprop-1-ynyl)benzyl]oxy]methyl}pyrimidine-2,4(1H,3H)-dione
• 英文别名: YML220；wild type HIV-1 inhibitor YML220；6-[(3,5-dimethylphenyl)-fluoromethyl]-5-ethyl-1-[[4-(3-hydroxyprop-1-ynyl)phenyl]methoxymethyl]pyrimidine-2,4-dione
• CAS: 1612757-29-5
• 化学式: C₂₆H₂₇FN₂O₄
• 分子量: 450.51
• InChiKey: GWIPJMRFEUZGDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyl-1-{[[4-(3-hydroxyprop-1-ynyl)benzyl]oxy]methyl}pyrimidine-2,4(1H,3H)-dione 在 2-碘酰基苯甲酸 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 以70%的产率得到3-{4-[((6-((3,5-dimethylphenyl)fluoromethyl)-5-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy)methyl]phenyl}propiolaldehyde
  参考文献：
  名称：

  Synthesis of Novel Fluoro Analogues of MKC442 as Microbicides

  摘要：

  Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative of compound 5 using propagyl alcohol to afford compound 12 (YML220). The latter compound was selected for further studies since it showed the most potent and selective activity in vitro against wild-type HIV-1 and non-nucleoside reverse transcriptase inhibitor-, nucleoside reverse transcriptase inhibitor-, and protease inhibitor-resistant mutants and a wide range of HIV-1 clinical isolates. 12 also showed microbicidal activity in long-term assays with heavily infected MT-4 cells.

  DOI：

  10.1021/jm500139a
• 作为产物：
  描述：

  2,4,6-三氯-5-乙基嘧啶 在 甲醇 、 sodium tetrahydroborate 、 N,O-双三甲硅基乙酰胺 、 二乙胺基三氟化硫 、 sodium 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 paraffin oil 为溶剂， 反应 61.75h， 生成 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyl-1-{[[4-(3-hydroxyprop-1-ynyl)benzyl]oxy]methyl}pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Synthesis of Novel Fluoro Analogues of MKC442 as Microbicides

  摘要：

  Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative of compound 5 using propagyl alcohol to afford compound 12 (YML220). The latter compound was selected for further studies since it showed the most potent and selective activity in vitro against wild-type HIV-1 and non-nucleoside reverse transcriptase inhibitor-, nucleoside reverse transcriptase inhibitor-, and protease inhibitor-resistant mutants and a wide range of HIV-1 clinical isolates. 12 also showed microbicidal activity in long-term assays with heavily infected MT-4 cells.

  DOI：

  10.1021/jm500139a

文献信息

• Synthesis of Novel Fluoro Analogues of MKC442 as Microbicides
  作者：Yasser M. Loksha、Erik B. Pedersen、Roberta Loddo、Giuseppina Sanna、Gabriella Collu、Gabriele Giliberti、Paolo La Colla

  DOI：10.1021/jm500139a

  日期：2014.6.26

  Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative of compound 5 using propagyl alcohol to afford compound 12 (YML220). The latter compound was selected for further studies since it showed the most potent and selective activity in vitro against wild-type HIV-1 and non-nucleoside reverse transcriptase inhibitor-, nucleoside reverse transcriptase inhibitor-, and protease inhibitor-resistant mutants and a wide range of HIV-1 clinical isolates. 12 also showed microbicidal activity in long-term assays with heavily infected MT-4 cells.