MC266 | 1011718-43-6

• 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: MC266
• 英文别名: 6,7-dimethoxy-2-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-3,4-dihydro-1H-isoquinoline
• CAS: 1011718-43-6
• 化学式: C₂₅H₃₃NO₃
• 分子量: 395.542
• InChiKey: HHPVCRYYLOFYGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6,7-二甲氧基-1,2,3,4-四氢异喹啉 、 4-(3-溴-n-丙基)-1,2-二氢-8-甲氧基萘 在 钯 氢气 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 MC266
  参考文献：
  名称：

  Small P-gp modulating molecules: SAR studies on tetrahydroisoquinoline derivatives

  摘要：

  The development of small molecules as P-gp modulating agents and SAR studies on these ligands represented the aim of the present work. A series of 6,7-dimethoxytetrahydroisoquinoline derivatives was prepared and their ability to inhibit P-gp activity has been evaluated. The basic nucleus of these compounds, common to the best P-gp inhibitors such as Tariquidar and Elacridar, has been functionalized with no-basic moiety from our studied sigma receptor ligands displaying potent P-gp inhibition. The best results were obtained for compounds 3c and 3a (EC50 = 1.64 and 4.86 mu M, respectively) and these results were remarkable because Elacridar showed in the same biological evaluation similar inhibitory activity (EC50 = 2 mu M). SAR studies displayed that the removal of double bond on the spacer or its shifting into tetraline ring decreased the P-gp inhibiting activity. Moreover, the P-gp inhibition mechanism of tested compounds was investigated by three selected biological experiments. The results displayed that only compound 3c was P-gp inhibitor as Elacridar, while compound 3a and reference compounds Cyclosporin A and Verapamil modulated P-gp activity saturating the efflux pump as substrates. Flow cytometry studies carried out in Doxorubicin resistant breast cancer cell line (MCF7/Adr) confirmed that compound 3c increased Doxorubicin cell accumulation 5.7-fold. In addition, in MCF7/ Adr, antiproliferative effect of 5 mu M Doxorubicin shifted from 5% to 95% when co-administered with compound 3c (20 mu M). The present study suggested a new class of small molecules displaying P-gp inhibitor activity differing from reference compounds Elacridar and Tariquidar for a simplified, and in the meantime, efficacious no-basic moiety. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.039

文献信息

• [EN] METHOD OF SCREENING FOR THERAPEUTIC COMPOUNDS USEFUL IN DETOXIFYING CENTRAL NERVOUS SYSTEM FROM B-AMYLOID PEPTIDE<br/>[FR] PROCÉDÉ DE CRIBLAGE POUR DÉTECTER DES COMPOSÉS THÉRAPEUTIQUES UTILES POUR LA DÉTOXIFICATION DU SYSTÈME NERVEUX CENTRAL EN PEPTIDE B-AMYLOÏDE
  申请人：UNIV BARI

  公开号：WO2012159674A1

  公开（公告）日：2012-11-29

  The present invention refers to a method and a kit of screening for therapeutic compounds useful in detoxifying central nervous system from β-amyloid peptide. The method and kit involve the use of the beta amyloid peptide in the everted gut sac assay and allow assessing the inducing activity of the test compounds on the P-gp-mediated β-amyloid peptide transport.
• Small P-gp modulating molecules: SAR studies on tetrahydroisoquinoline derivatives
  作者：Nicola Antonio Colabufo、Francesco Berardi、Mariangela Cantore、Maria Grazia Perrone、Marialessandra Contino、Carmela Inglese、Mauro Niso、Roberto Perrone、Amalia Azzariti、Grazia Maria Simone、Letizia Porcelli、Angelo Paradiso

  DOI：10.1016/j.bmc.2007.09.039

  日期：2008.1

  The development of small molecules as P-gp modulating agents and SAR studies on these ligands represented the aim of the present work. A series of 6,7-dimethoxytetrahydroisoquinoline derivatives was prepared and their ability to inhibit P-gp activity has been evaluated. The basic nucleus of these compounds, common to the best P-gp inhibitors such as Tariquidar and Elacridar, has been functionalized with no-basic moiety from our studied sigma receptor ligands displaying potent P-gp inhibition. The best results were obtained for compounds 3c and 3a (EC50 = 1.64 and 4.86 mu M, respectively) and these results were remarkable because Elacridar showed in the same biological evaluation similar inhibitory activity (EC50 = 2 mu M). SAR studies displayed that the removal of double bond on the spacer or its shifting into tetraline ring decreased the P-gp inhibiting activity. Moreover, the P-gp inhibition mechanism of tested compounds was investigated by three selected biological experiments. The results displayed that only compound 3c was P-gp inhibitor as Elacridar, while compound 3a and reference compounds Cyclosporin A and Verapamil modulated P-gp activity saturating the efflux pump as substrates. Flow cytometry studies carried out in Doxorubicin resistant breast cancer cell line (MCF7/Adr) confirmed that compound 3c increased Doxorubicin cell accumulation 5.7-fold. In addition, in MCF7/ Adr, antiproliferative effect of 5 mu M Doxorubicin shifted from 5% to 95% when co-administered with compound 3c (20 mu M). The present study suggested a new class of small molecules displaying P-gp inhibitor activity differing from reference compounds Elacridar and Tariquidar for a simplified, and in the meantime, efficacious no-basic moiety. (c) 2007 Elsevier Ltd. All rights reserved.