2-amino-N-[3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl]benzamide | 916993-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-amino-N-[3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl]benzamide
• 英文别名: 2-amino-N-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propyl]benzamide
• CAS: 916993-92-5
• 化学式: C₂₁H₂₇N₃O₃
• 分子量: 369.464
• InChiKey: UWLNPPUWTRQLPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-N-[3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl]benzamide 、 3-喹啉羰酰氯 在 Dowex 1X₈ chloride resin 作用下， 以 二氯甲烷 为溶剂， 反应 30.0h， 以42%的产率得到
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

  DOI：

  10.1016/j.bmc.2006.07.055
• 作为产物：
  描述：

  6,7-二甲氧基-1,2,3,4-四氢异喹啉 在 sodium hydroxide 、 氢气 、 镍 、 sodium carbonate 、 sodium iodide 作用下， 以 乙醇 、 乙腈 、 叔丁醇 为溶剂， 反应 54.0h， 生成 2-amino-N-[3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl]benzamide
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

  DOI：

  10.1016/j.bmc.2006.07.055

文献信息

• In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450
  作者：Philippe Labrie、Shawn. P. Maddaford、Jacques Lacroix、Concettina Catalano、David K.H. Lee、Suman Rakhit、René C. Gaudreault

  DOI：10.1016/j.bmc.2006.07.055

  日期：2006.12

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.