ethyl 4-(4-fluorophenyl)-1,2,3,4-tetrahydro-2-oxo-6-phenylpyrimidine-5-carboxylate | 397882-37-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 4-(4-fluorophenyl)-1,2,3,4-tetrahydro-2-oxo-6-phenylpyrimidine-5-carboxylate
• 英文别名: ethyl 4-(4-fluorophenyl)-2-oxo-6-phenyl-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 397882-37-0
• 化学式: C₁₉H₁₇FN₂O₃
• 分子量: 340.354
• InChiKey: VPUTVESIIZOZEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-fluorophenyl)-1,2,3,4-tetrahydro-2-oxo-6-phenylpyrimidine-5-carboxylate 在 硝酸 、 caesium carbonate 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 4-[4-[[5-ethoxycarbonyl-4-(4-fluorophenyl)-2-oxo-6-phenyl-pyrimidin-1-yl]methyl]phenyl]-2-hydroxy-4-oxo-but-2-enoic acid
  参考文献：
  名称：

  Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

  摘要：

  The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl alpha, gamma-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the beta-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c' exhibited an anti-HIV activity of 0.19 mu M in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.015
• 作为产物：
  描述：

  对氟苯甲醛 、 苯甲酰乙酸乙酯 、 尿素 在 cerium(III) chloride heptahydrate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 ethyl 4-(4-fluorophenyl)-1,2,3,4-tetrahydro-2-oxo-6-phenylpyrimidine-5-carboxylate
  参考文献：
  名称：

  Efficient aerobic oxidative dehydrogenation of dihydropyrimidinones and dihydropyrimidines

  摘要：

  4-Substituted dihydropyrimidinones and dihydropyrimidines were first efficient aerobic oxidized to the corresponding pyrimidinones and pyrimidines, respectively, in high yields by molecular oxygen in the presence of catalytic amount of N-hydroxyphthalimide (NHPI) and Co(OAc)(2) in a mild and environmental benign condition. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.105

文献信息

• Efficient aerobic oxidative dehydrogenation of dihydropyrimidinones and dihydropyrimidines
  作者：Bing Han、Run-Feng Han、Yu-Wei Ren、Xiao-Yong Duan、Yi-Chuan Xu、Wei Zhang

  DOI：10.1016/j.tet.2011.05.105

  日期：2011.8

  4-Substituted dihydropyrimidinones and dihydropyrimidines were first efficient aerobic oxidized to the corresponding pyrimidinones and pyrimidines, respectively, in high yields by molecular oxygen in the presence of catalytic amount of N-hydroxyphthalimide (NHPI) and Co(OAc)(2) in a mild and environmental benign condition. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase
  作者：Ozkan Sari、Vincent Roy、Mathieu Métifiot、Christophe Marchand、Yves Pommier、Stéphane Bourg、Pascal Bonnet、Raymond F. Schinazi、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2015.09.015

  日期：2015.11

  The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl alpha, gamma-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the beta-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c' exhibited an anti-HIV activity of 0.19 mu M in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity. (C) 2015 Elsevier Masson SAS. All rights reserved.