1-[(3E)-3-(5-methoxy-3,4-dihydro-2H-naphthalen-1-ylidene)propyl]piperidine | 1011718-30-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-[(3E)-3-(5-methoxy-3,4-dihydro-2H-naphthalen-1-ylidene)propyl]piperidine
• CAS: 1011718-30-1
• 化学式: C₁₉H₂₇NO
• 分子量: 285.429
• InChiKey: OQZQEGAAANHHRE-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  哌啶 、 (E)-1-(3-chloro-4-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以88%的产率得到1-[(3E)-3-(5-methoxy-3,4-dihydro-2H-naphthalen-1-ylidene)propyl]piperidine
  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

• 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.