RECEPTOR AFFINITY AND PHOSPHODIESTERASES 4B AND 10A ACTIVITY OF OCTAHYDRO- AND 6,7-DIMETHOXY-3,4-DIHYDRO- ISOQUINOLIN-2(1H)-YL-ALKYL DERIVATIVES OF IMIDAZO- AND PYRIMIDINO[2,1-f]PURINES

Acta Pol Pharm. 2016 Mar-Apr;73(2):369-77.

Abstract

A series of octahydro- and 6,7-dimethoxy-3,4-dihydro- isoquinolin-2(1H)-yl-alkyl derivatives of imidazo- and pyrimidino[2,1-f]purines were synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT(1A), 5-HT(6), 5-HT(7), and dopamine D2 receptors and inhibitory potencies for phosphodiesterases - PDE4B1 and PDE10A. The structure-activity relationships allowed to determine the structural features responsible for receptor and enzyme activity. Compound 5 (8-(4-(6,7-dimethoxy-3,4-dihydroiso- quinolin-2(1H)butyl)1,3-dimethyl-H-imidazo[2,1-f]purine-2,4(3H,8H)-dione) could be regarded as promising structure for further modification and detailed mechanistic study for obtained hybrid ligands.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • HEK293 Cells
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / metabolism*
  • Imidazoles / pharmacology
  • Ligands
  • Molecular Structure
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / metabolism*
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / metabolism*
  • Protein Binding
  • Pyrimidinones / chemistry
  • Pyrimidinones / metabolism*
  • Pyrimidinones / pharmacology
  • Radioligand Assay
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship
  • Transfection

Substances

  • DRD2 protein, human
  • Imidazoles
  • Ligands
  • Phosphodiesterase 4 Inhibitors
  • Pyrimidinones
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Phosphoric Diester Hydrolases