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

N A Saccomano; F J Vinick; B K Koe; J A Nielsen; W M Whalen; M Meltz; D Phillips; P F Thadieo; S Jung; D S Chapin

doi:10.1021/jm00105a045

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.

Authors

N A Saccomano¹, F J Vinick, B K Koe, J A Nielsen, W M Whalen, M Meltz, D Phillips, P F Thadieo, S Jung, D S Chapin, et al.

Affiliation

¹ Central Research, Pfizer Inc., Groton, Connecticut 06340.

PMID: 1992129
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