4-((6-methoxy-4-(2,6-dimethylphenoxy)pyridin-2-yl)amino)benzonitrile | 1580002-12-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-((6-methoxy-4-(2,6-dimethylphenoxy)pyridin-2-yl)amino)benzonitrile
• 英文别名: 4-[[4-(2,6-Dimethylphenoxy)-6-methoxy-2-pyridyl]amino]benzonitrile；4-[[4-(2,6-dimethylphenoxy)-6-methoxypyridin-2-yl]amino]benzonitrile
• CAS: 1580002-12-5
• 化学式: C₂₁H₁₉N₃O₂
• 分子量: 345.401
• InChiKey: HRJXVYLNOIKMLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((6-methoxy-4-(2,6-dimethylphenoxy)pyridin-2-yl)amino)benzonitrile 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 以86%的产率得到4-((4-(2,6-dimethylphenoxy)-6-oxo-1,6-dihydropyridin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays

  摘要：

  Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino) pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 = 0.15-0.84 mu M), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.054
• 作为产物：
  描述：

  2,4,6-三氯吡啶 在 sodium methylate 、 palladium diacetate 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 4-((6-methoxy-4-(2,6-dimethylphenoxy)pyridin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays

  摘要：

  Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino) pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 = 0.15-0.84 mu M), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.054

文献信息

• Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays
  作者：Wenmin Chen、Peng Zhan、Diwakar Rai、Erik De Clercq、Christophe Pannecouque、Jan Balzarini、Zhongxia Zhou、Huiqing Liu、Xinyong Liu

  DOI：10.1016/j.bmc.2014.01.054

  日期：2014.3

  Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino) pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 = 0.15-0.84 mu M), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives. (C) 2014 Elsevier Ltd. All rights reserved.