3-{4-[4-(3,4-methylenedioxyphenyl)-1,2,3,6-tetrahydropyridinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 3-{4-[4-(3,4-methylenedioxyphenyl)-1,2,3,6-tetrahydropyridinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil
• 英文别名: 3-[4-[4-(1,3-benzodioxol-5-yl)-3,6-dihydro-2H-pyridin-1-yl]butyl]-6-(3-ethyl-4-methylanilino)-1H-pyrimidine-2,4-dione
• 化学式: C₂₉H₃₄N₄O₄
• 分子量: 502.613
• InChiKey: SUEINQHMFXVCOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-1,2-亚甲二氧基苯 在 仲丁基锂 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 环己烷 、 丙酮 为溶剂， 反应 28.0h， 生成 3-{4-[4-(3,4-methylenedioxyphenyl)-1,2,3,6-tetrahydropyridinyl]butyl}-6-(3-ethyl-4-methylanilino)uracil
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of 3-Substituted-6-(3-ethyl-4-methylanilino)uracils

  摘要：

  Numerous 3-substituted-6-(3-ethyl-4-methylanilino)uracils (EMAU) have been synthesized and screened for their capacity to inhibit the replication-specific bacterial DNA polymerase IIIC (pol IIIC) and the growth of Gram+ bacteria in culture. Direct alkylation of 2-methoxy-6-amino-4-pyrimidone produced the N3-substituted derivatives, which were separated from the byproduct 4-alkoxy analogues. The N3-substituted derivatives were heated with a mixture of 3-ethyl-4-methylaniline and its hydrochloride to effect displacement of the 6-amino group and simultaneous demethylation of the 2-methoxy group to yield target compounds in good yields. Certain intermediates, e.g. the 3-(iodoalkyl) compounds, were converted to a variety of (3-substituted-alkyl)-EMAUs by displacement. Most compounds were potent competitive inhibitors of pol IIIC (K(i)s 0.02-0.5 mu M), and those with neutral, moderately polar 3-substituents had potent antibacterial activity against Gram+ organisms in culture (MICs 0.125-10 mu g/mL). Several compounds protected mice from lethal intraperitoneal (ip) infections with S. aureus (Smith) when given by the ip route. A water soluble derivative, 3-(4-morpholinylbutyl)-EMAU hydrochloride, given subcutaneously, prolonged the life of infected mice in a dose dependent manner.

  DOI：

  10.1021/jm050517r

文献信息

• Synthesis and Antibacterial Activity of 3-Substituted-6-(3-ethyl-4-methylanilino)uracils
  作者：Chengxin Zhi、Zheng-yu Long、Andrzej Manikowski、Neal C. Brown、Paul M. Tarantino,、Karsten Holm、Edward J. Dix、George E. Wright、Kim A. Foster、Michelle M. Butler、William A. LaMarr、Donna J. Skow、Irina Motorina、Serge Lamothe、Richard Storer

  DOI：10.1021/jm050517r

  日期：2005.11.1

  Numerous 3-substituted-6-(3-ethyl-4-methylanilino)uracils (EMAU) have been synthesized and screened for their capacity to inhibit the replication-specific bacterial DNA polymerase IIIC (pol IIIC) and the growth of Gram+ bacteria in culture. Direct alkylation of 2-methoxy-6-amino-4-pyrimidone produced the N3-substituted derivatives, which were separated from the byproduct 4-alkoxy analogues. The N3-substituted derivatives were heated with a mixture of 3-ethyl-4-methylaniline and its hydrochloride to effect displacement of the 6-amino group and simultaneous demethylation of the 2-methoxy group to yield target compounds in good yields. Certain intermediates, e.g. the 3-(iodoalkyl) compounds, were converted to a variety of (3-substituted-alkyl)-EMAUs by displacement. Most compounds were potent competitive inhibitors of pol IIIC (K(i)s 0.02-0.5 mu M), and those with neutral, moderately polar 3-substituents had potent antibacterial activity against Gram+ organisms in culture (MICs 0.125-10 mu g/mL). Several compounds protected mice from lethal intraperitoneal (ip) infections with S. aureus (Smith) when given by the ip route. A water soluble derivative, 3-(4-morpholinylbutyl)-EMAU hydrochloride, given subcutaneously, prolonged the life of infected mice in a dose dependent manner.