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

Authors:
  • FVFrederic J. Vinick
    Frederic J. Vinick
  • BKB. Kenneth Koe
    B. Kenneth Koe
  • JNJann A. Nielsen
    Jann A. Nielsen
  • WWWilliam M. Whalen
    William M. Whalen
  • MMMorgan Meltz
    Morgan Meltz
  • DPDouglas Phillips
    Douglas Phillips
  • PTPeter F. Thadieo
    Peter F. Thadieo
  • SJStanley Jung
    Stanley Jung
  • DCDouglas C. Chapin
    Douglas C. Chapin
  • LLLorraine A. Lebel
    Lorraine A. Lebel
  • LRLorena L. Russo
    Lorena L. Russo
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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.