6-(2,4,6-trimethylphenoxy)-N-(2,4,6-trimethylphenyl)pyrimidin-4-amine | 1416447-07-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2,4,6-trimethylphenoxy)-N-(2,4,6-trimethylphenyl)pyrimidin-4-amine
• CAS: 1416447-07-8
• 化学式: C₂₂H₂₅N₃O
• 分子量: 347.46
• InChiKey: AGKZVPXIDDBVMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4,6-三甲酚 在 18-冠醚-6 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 6-(2,4,6-trimethylphenoxy)-N-(2,4,6-trimethylphenyl)pyrimidin-4-amine
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modeling of 4,6-diarylpyrimidines and diarylbenzenes as novel non-nucleosides HIV-1 reverse transcriptase inhibitors

  摘要：

  A series of novel 4,6-diarylpyrimidines (4,6-DAPY) and diarylbenzenes (DABE) compounds were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 8b, 8d, 14b and 18 (EC50 = 0.049, 0.381, 0.599 and 0.398 mu M, respectively), with HIV-1 inhibitory activity improved or similar to nevirapine (NVP, EC50 = 0.097 mu M) and delavirdine (DEV, EC50 = 0.55 mu M). The other compounds displayed moderate activity (8c, EC50 = 5.25 mu M) or were inactive (8a and 14a) against HIV-1 replication. Molecular modeling studies were performed with the synthesized compounds in complex with the wild-type reverse transcriptase (RT). A correlation was found between the anti-HIV activity and the electrostatic energy of interaction with Lys101 residue. These findings enrich the SAR of these Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) families. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.036

文献信息

• Synthesis, biological evaluation and molecular modeling of 4,6-diarylpyrimidines and diarylbenzenes as novel non-nucleosides HIV-1 reverse transcriptase inhibitors
  作者：Sergio R. Ribone、Volker Leen、Marcela Madrid、Wim Dehaen、Dirk Daelemans、Christophe Pannecouque、Margarita C. Briñón

  DOI：10.1016/j.ejmech.2012.10.036

  日期：2012.12

  A series of novel 4,6-diarylpyrimidines (4,6-DAPY) and diarylbenzenes (DABE) compounds were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 8b, 8d, 14b and 18 (EC50 = 0.049, 0.381, 0.599 and 0.398 mu M, respectively), with HIV-1 inhibitory activity improved or similar to nevirapine (NVP, EC50 = 0.097 mu M) and delavirdine (DEV, EC50 = 0.55 mu M). The other compounds displayed moderate activity (8c, EC50 = 5.25 mu M) or were inactive (8a and 14a) against HIV-1 replication. Molecular modeling studies were performed with the synthesized compounds in complex with the wild-type reverse transcriptase (RT). A correlation was found between the anti-HIV activity and the electrostatic energy of interaction with Lys101 residue. These findings enrich the SAR of these Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) families. (C) 2012 Elsevier Masson SAS. All rights reserved.