3,5-dimethyl-4-(5-nitro-2-(p-tolylamino)pyridin-4-yloxy)benzonitrile | 1585274-70-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,5-dimethyl-4-(5-nitro-2-(p-tolylamino)pyridin-4-yloxy)benzonitrile
• 英文别名: 3,5-Dimethyl-4-[[2-(4-methylanilino)-5-nitro-4-pyridyl]oxy]benzonitrile；3,5-dimethyl-4-[2-(4-methylanilino)-5-nitropyridin-4-yl]oxybenzonitrile
• CAS: 1585274-70-9
• 化学式: C₂₁H₁₈N₄O₃
• 分子量: 374.399
• InChiKey: PTCCWGNZMKMHBA-UHFFFAOYSA-N

物化性质

• 熔点：
  237-240 °C
• 沸点：
  542.7±50.0 °C(predicted)
• 密度：
  1.31±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-4-氯吡啶 在 硫酸 、 硝酸 、 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 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,5-dimethyl-4-(5-nitro-2-(p-tolylamino)pyridin-4-yloxy)benzonitrile
  参考文献：
  名称：

  Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a structure-based core refining approach

  摘要：

  As a continuation of our efforts to discover and develop back-up analogs of DAPYs, novel substituted nitropyridine derivatives were designed via a structure-based core refining approach, synthesized and evaluated for their in vitro HIV-1 activity in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against wild-type HIV-1 IIIB. Most notably, the compound 7b was identified as the most promising candidate in inhibiting HIV-1 replication with an EC50 value of 0.056 mu M and a selective index (SI) of 1251, which were much better than those of NVP (EC50 = 0.23 mu M) and DLV (EC50 = 0.51 mu M). Some other compounds, 7k, 7c, 7j and 7e, were also endowed with a favorable anti-HIV-1 potency (EC50 = 0.034, 0.11, 0.11 and 0.16 mu M, respectively). Some antivirally active compounds also showed moderate inhibitory activity against RT. Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogs provide valuable avenues for future molecular optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.047

文献信息

• Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a structure-based core refining approach
  作者：Jun Wang、Peng Zhan、Zhenyu Li、Huiqing Liu、Erik De Clercq、Christophe Pannecouque、Xinyong Liu

  DOI：10.1016/j.ejmech.2014.02.047

  日期：2014.4

  As a continuation of our efforts to discover and develop back-up analogs of DAPYs, novel substituted nitropyridine derivatives were designed via a structure-based core refining approach, synthesized and evaluated for their in vitro HIV-1 activity in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against wild-type HIV-1 IIIB. Most notably, the compound 7b was identified as the most promising candidate in inhibiting HIV-1 replication with an EC50 value of 0.056 mu M and a selective index (SI) of 1251, which were much better than those of NVP (EC50 = 0.23 mu M) and DLV (EC50 = 0.51 mu M). Some other compounds, 7k, 7c, 7j and 7e, were also endowed with a favorable anti-HIV-1 potency (EC50 = 0.034, 0.11, 0.11 and 0.16 mu M, respectively). Some antivirally active compounds also showed moderate inhibitory activity against RT. Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogs provide valuable avenues for future molecular optimization. (C) 2014 Elsevier Masson SAS. All rights reserved.