N-(3-chlorophenyl)-2-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-chlorophenyl)-2-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)acetamide
• 英文别名: N-(3-chlorophenyl)-2-[2-(4-cyanoanilino)pyrimidin-4-yl]oxy-acetamide；N-(3-chlorophenyl)-2-[2-(4-cyanoanilino)pyrimidin-4-yl]oxyacetamide
• 化学式: C₁₉H₁₄ClN₅O₂
• 分子量: 379.805
• InChiKey: ADPNBORQUUAXCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氨基苯腈 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 N-(3-chlorophenyl)-2-((2-((4-cyanophenyl)amino)pyrimidin-4-yl)oxy)acetamide
  参考文献：
  名称：

  Synthesis and biological evaluation of DAPY–DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase

  摘要：

  A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Many promising candidates with potent inhibitory activity (wild-type) within the EC50 range from 0.16 to 0.013 mu M were obtained. In particular, 3c, 3p, 3r and 3s displayed low nM level EC50 values (35, 13, 50 and 17 nM, respectively) and high selectivity (9342, 25131, 2890 and 11338, respectively), which were much more potent than NVP (EC50 = 0.31 mu M, SI = 48), 3TC (EC50 = 2.24 mu M, SI > 39), DDI (EC50 = 23.20 mu M, SI > 9) and DLV (EC50 = 0.65 mu M, SI > 67), and comparable to AZT (EC50 = 0.0071 mu M, SI > 13144) and EFV (EC50 = 0.0062 mu M, SI > 1014). The HIV-1 reverse transcriptase inhibitory assay confirmed that these DAPY-DPEs hybrids targeted HIV-1 RT. Molecular simulation was performed to investigate the potential binding mode of the newly synthesized compounds. And reasonable explanation for the activity results was discussed with docking method. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.032

文献信息

• Synthesis and biological evaluation of DAPY–DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase
  作者：Hai-Qiu Wu、Jin Yao、Qiu-Qin He、Wen-Xue Chen、Fen-Er Chen、Christophe Pannecouque、Erik De Clercq、Dirk Daelemans

  DOI：10.1016/j.bmc.2014.11.032

  日期：2015.2

  A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Many promising candidates with potent inhibitory activity (wild-type) within the EC50 range from 0.16 to 0.013 mu M were obtained. In particular, 3c, 3p, 3r and 3s displayed low nM level EC50 values (35, 13, 50 and 17 nM, respectively) and high selectivity (9342, 25131, 2890 and 11338, respectively), which were much more potent than NVP (EC50 = 0.31 mu M, SI = 48), 3TC (EC50 = 2.24 mu M, SI > 39), DDI (EC50 = 23.20 mu M, SI > 9) and DLV (EC50 = 0.65 mu M, SI > 67), and comparable to AZT (EC50 = 0.0071 mu M, SI > 13144) and EFV (EC50 = 0.0062 mu M, SI > 1014). The HIV-1 reverse transcriptase inhibitory assay confirmed that these DAPY-DPEs hybrids targeted HIV-1 RT. Molecular simulation was performed to investigate the potential binding mode of the newly synthesized compounds. And reasonable explanation for the activity results was discussed with docking method. (C) 2014 Elsevier Ltd. All rights reserved.