3,4-dihydro-8-hydroxy-6-methoxy-2-(3-(piperidin-1-ylcarbonyl)phenyl)-isoquinolin-1-(2H)-one

• 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: 3,4-dihydro-8-hydroxy-6-methoxy-2-(3-(piperidin-1-ylcarbonyl)phenyl)-isoquinolin-1-(2H)-one
• 英文别名: 8-Hydroxy-6-methoxy-2-[3-(piperidine-1-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one；8-hydroxy-6-methoxy-2-[3-(piperidine-1-carbonyl)phenyl]-3,4-dihydroisoquinolin-1-one
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: BDJUXSUNWGHGSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5,7-二甲氧基茚酮 在 copper(l) iodide 、 sodium azide 、 lithium chloride hydrate 、 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 10.0h， 生成 3,4-dihydro-8-hydroxy-6-methoxy-2-(3-(piperidin-1-ylcarbonyl)phenyl)-isoquinolin-1-(2H)-one
  参考文献：
  名称：

  Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR inhibitor by scaffold hopping

  摘要：

  2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against two human cancer cell lines, including A431 and A549. The SAR of the title compounds was preliminarily discussed. The compounds with ideal inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed the best activity against A431 and EGFR tyrosine kinase. These findings suggest that title compounds are EGFR inhibitors with novel structures. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.027

文献信息

• Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR inhibitor by scaffold hopping
  作者：Bo-Rui Kang、Ai-Lin Shan、Yi-Ping Li、Jing Xu、She-Min Lu、San-Qi Zhang

  DOI：10.1016/j.bmc.2013.09.027

  日期：2013.11

  2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against two human cancer cell lines, including A431 and A549. The SAR of the title compounds was preliminarily discussed. The compounds with ideal inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed the best activity against A431 and EGFR tyrosine kinase. These findings suggest that title compounds are EGFR inhibitors with novel structures. (C) 2013 Elsevier Ltd. All rights reserved.