1-[(E)-3-chloroprop-1-ylidene]-7-methoxy-1,2,3,4-tetrahydronaphthalene | 1011718-35-6

• 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-[(E)-3-chloroprop-1-ylidene]-7-methoxy-1,2,3,4-tetrahydronaphthalene
• CAS: 1011718-35-6
• 化学式: C₁₄H₁₇ClO
• 分子量: 236.741
• InChiKey: CISGYIIHZHSZLQ-IZZDOVSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  1-[(E)-3-chloroprop-1-ylidene]-7-methoxy-1,2,3,4-tetrahydronaphthalene 、 6,7-二甲氧基-1,2,3,4-四氢异喹啉 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到N-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-(1E)-propyliden-3-yl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  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
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 、 环丙基溴化镁 在 盐酸 作用下， 生成 1-[(E)-3-chloroprop-1-ylidene]-7-methoxy-1,2,3,4-tetrahydronaphthalene
  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