4-[(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)methyl]-2-(6-fluoronaphthalen-2-yl)-1,3-thiazole | 1424835-41-5

• 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: 4-[(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)methyl]-2-(6-fluoronaphthalen-2-yl)-1,3-thiazole
• CAS: 1424835-41-5
• 化学式: C₂₅H₂₃FN₂O₂S
• 分子量: 434.534
• InChiKey: OBGNPEXZGGPLOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-fluoro-2-naphthoyl chloride 在 劳森试剂 、 ammonium hydroxide 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-[(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)methyl]-2-(6-fluoronaphthalen-2-yl)-1,3-thiazole
  参考文献：
  名称：

  Naphthalenyl derivatives for hitting P-gp/MRP1/BCRP transporters

  摘要：

  Substituted naphthalenyl derivatives bearing oxazole, or thiazole or furyl heteronuclei have been carried out as bioisosters of aryl-oxazoles and -thiazoles derivatives previously reported in order to investigate the role of the hindrance on the activity towards P-gp/BCRP/and MRP1 transporters. In addition, the role of naphthalenyl group to modulate P-gp intrinsic activity of these compounds was ascertained.The results demonstrated that all naphthalenyl derivatives displayed comparable P-gp activity with respect to lead compounds previously characterized in our SAR studies but were less active towards BCRP and MRP1 pumps. In terms of intrinsic activity, the replacement of aryl with naphthalenyl moiety led to P-gp inhibitors, unambiguous or ambiguous substrates on the base of the heteronucleus and the substituent on the naphthalenyl fragment. Indeed, oxazole derivatives were: inhibitors (R = H, F, OH), unambiguous substrates (R = OCH3), or ambiguous substrate (R = Br); thiazole derivatives were: unambiguous substrates (R = OCH3, Br), or ambiguous substrates (R = H, F). Finally furyl derivatives were ambiguous substrates. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.021

文献信息

• Naphthalenyl derivatives for hitting P-gp/MRP1/BCRP transporters
  作者：Nicola A. Colabufo、Marialessandra Contino、Mariangela Cantore、Elena Capparelli、Maria Grazia Perrone、Giuseppe Cassano、Giuseppe Gasparre、Marcello Leopoldo、Francesco Berardi、Roberto Perrone

  DOI：10.1016/j.bmc.2012.12.021

  日期：2013.3

  Substituted naphthalenyl derivatives bearing oxazole, or thiazole or furyl heteronuclei have been carried out as bioisosters of aryl-oxazoles and -thiazoles derivatives previously reported in order to investigate the role of the hindrance on the activity towards P-gp/BCRP/and MRP1 transporters. In addition, the role of naphthalenyl group to modulate P-gp intrinsic activity of these compounds was ascertained.The results demonstrated that all naphthalenyl derivatives displayed comparable P-gp activity with respect to lead compounds previously characterized in our SAR studies but were less active towards BCRP and MRP1 pumps. In terms of intrinsic activity, the replacement of aryl with naphthalenyl moiety led to P-gp inhibitors, unambiguous or ambiguous substrates on the base of the heteronucleus and the substituent on the naphthalenyl fragment. Indeed, oxazole derivatives were: inhibitors (R = H, F, OH), unambiguous substrates (R = OCH3), or ambiguous substrate (R = Br); thiazole derivatives were: unambiguous substrates (R = OCH3, Br), or ambiguous substrates (R = H, F). Finally furyl derivatives were ambiguous substrates. (C) 2013 Elsevier Ltd. All rights reserved.