N-(4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenyl)-2-amino-4,5-dimethoxybenzamide | 937701-86-5

• 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-(4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenyl)-2-amino-4,5-dimethoxybenzamide
• CAS: 937701-86-5
• 化学式: C₂₈H₃₄N₄O₅
• 分子量: 506.602
• InChiKey: CSCXTEBMZKVIIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  98.52
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-(4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenyl)-2-amino-4,5-dimethoxybenzamide 、 3-喹啉羰酰氯 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以61%的产率得到N-(2-((4-(4-(3,4-dimethoxybenzyl)piperazin-1-yl)phenyl)carbamoyl)-4,5dimethoxyphenyl)quinoline-3-carboxamide
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.03.014
• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 对甲苯磺酸甲酯 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、262.01 kPa 条件下， 反应 72.0h， 生成 N-(4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenyl)-2-amino-4,5-dimethoxybenzamide
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.03.014