Design and synthesis of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3652-5. doi: 10.1016/j.bmcl.2008.04.082. Epub 2008 May 11.

Abstract

Exploration for new MDR-modulator utilizing tetrahydroisoquinoline as scaffold disclosed 6,7-dimethoxy-1-(3,4-dimethoxy)benzyl-2-(N-n-octyl-N'-cyano)guanyl-1,2,3,4-tetrahydroisoquinoline (7) as a readily accessible medicinal lead. Compound 7 possessed potent MDR reversal activity in the range of the reference compound verapamil, and had not cardiovascular activity compared to verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines* / chemical synthesis
  • Amidines* / chemistry
  • Amidines* / pharmacology
  • Animals
  • Anti-Arrhythmia Agents / chemical synthesis
  • Anti-Arrhythmia Agents / chemistry
  • Anti-Arrhythmia Agents / pharmacology
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Arrhythmias, Cardiac / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Humans
  • Isoquinolines* / chemical synthesis
  • Isoquinolines* / chemistry
  • Isoquinolines* / pharmacology
  • Mice
  • Mice, Nude
  • Myocardial Contraction / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines* / chemical synthesis
  • Tetrahydroisoquinolines* / chemistry
  • Tetrahydroisoquinolines* / pharmacology
  • Time Factors
  • Verapamil / adverse effects
  • Verapamil / pharmacology
  • Verapamil / therapeutic use

Substances

  • 6,7-dimethoxy-1-(3,4-dimethoxy)benzyl-2-(N-n-octyl-N'-cyano)guanyl-1,2,3,4-tetrahydroisoquinoline
  • Amidines
  • Anti-Arrhythmia Agents
  • Antineoplastic Agents
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Verapamil