Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones

J Med Chem. 1991 Jan;34(1):291-8. doi: 10.1021/jm00105a045.

Abstract

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / chemical synthesis*
  • Body Temperature / drug effects
  • Brain / metabolism*
  • Calcium / pharmacology
  • Cerebral Cortex / enzymology*
  • Female
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Conformation
  • Molecular Structure
  • Motor Activity / drug effects
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Reserpine / pharmacology
  • Rolipram
  • Structure-Activity Relationship

Substances

  • Antidepressive Agents
  • Indicators and Reagents
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Reserpine
  • Rolipram
  • Calcium