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

• Published in: Journal of medicinal chemistry 1991, Vol.34 (1), p.291-298
• Main Authors: SACCOMANO, N. A, VINICK, F. J, LEBEL, L. A, RUSSO, L. L, HELWEG, D. A, JOHNSON, J. L, IVES, J. L, WILLIAMS, I. H, KOE, B. K, NIELSEN, J. A, WHALEN, W. M, MELTZ, M, PHILLIPS, D, THADIEO, P. F, JUNG, S, CHAPIN, D. S
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - chemical synthesis; Body Temperature - drug effects; Brain - metabolism; Calcium - pharmacology; Cerebral Cortex - enzymology; Chemistry; Exact sciences and technology; Female; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mice; Molecular Conformation; Molecular Structure; Motor Activity - drug effects; Organic chemistry; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Preparations and properties; Pyrrolidinones - pharmacology; Rats; Rats, Inbred Strains; Reserpine - pharmacology; Rolipram; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00105a045

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.