6-((4-cyanophenyl)amino)-N-(2,2-dimethoxyethyl)-4-(mesityloxy)nicotinamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-((4-cyanophenyl)amino)-N-(2,2-dimethoxyethyl)-4-(mesityloxy)nicotinamide
• 英文别名: 6-(4-cyanoanilino)-N-(2,2-dimethoxyethyl)-4-(2,4,6-trimethylphenoxy)pyridine-3-carboxamide
• 化学式: C₂₆H₂₈N₄O₄
• 分子量: 460.533
• InChiKey: LRVKRUCIERAMLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4,6-二羟基烟酸乙酯 在 三甲基铝 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 54.25h， 生成 6-((4-cyanophenyl)amino)-N-(2,2-dimethoxyethyl)-4-(mesityloxy)nicotinamide
  参考文献：
  名称：

  Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization

  摘要：

  Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells together with the inhibition against the reverse transcriptase (RT) in an enzymatic assay. Encouragingly, most of the new DANAs were found to be active against wild-type HIV-1 with an EC50 in the range of 0.027-4.54 mu M, Among them, compound 6b11 (EC50 = 0.027 mu M, SI > 12518) and 6b5 (EC50 = 0.029 mu M, SI = 2471) were identified as the most potent inhibitors, which were more potent than the reference drugs nevirapine (EC50 = 0.31 mu M) and delavirdine (EC50 = 0.66 mu M). Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. Compound 6b11 exhibited the highest enzymatic inhibition activity (IC50 = 20 nM), which is equal to that of efavirenz (EC50 = 20 nM) and 31 times higher than that of nevirapine (EC50 = 0.62 mu M). Preliminary structure-activity relationships (SARs) and molecular modeling of these new DANAs have been discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.054

文献信息

• Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization
  作者：Zhaoqiang Liu、Wenmin Chen、Peng Zhan、Erik De Clercq、Christophe Pannecouque、Xinyong Liu

  DOI：10.1016/j.ejmech.2014.09.054

  日期：2014.11

  Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells together with the inhibition against the reverse transcriptase (RT) in an enzymatic assay. Encouragingly, most of the new DANAs were found to be active against wild-type HIV-1 with an EC50 in the range of 0.027-4.54 mu M, Among them, compound 6b11 (EC50 = 0.027 mu M, SI > 12518) and 6b5 (EC50 = 0.029 mu M, SI = 2471) were identified as the most potent inhibitors, which were more potent than the reference drugs nevirapine (EC50 = 0.31 mu M) and delavirdine (EC50 = 0.66 mu M). Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. Compound 6b11 exhibited the highest enzymatic inhibition activity (IC50 = 20 nM), which is equal to that of efavirenz (EC50 = 20 nM) and 31 times higher than that of nevirapine (EC50 = 0.62 mu M). Preliminary structure-activity relationships (SARs) and molecular modeling of these new DANAs have been discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.