title: Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.
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.
authors.affiliation: Central Research, Pfizer Inc., Groton, Connecticut 06340.
authors.forename: N A
authors.initials: NA
authors.lastname: Saccomano
authors.forename: F J
authors.initials: FJ
authors.lastname: Vinick
authors.forename: B K
authors.initials: BK
authors.lastname: Koe
authors.forename: J A
authors.initials: JA
authors.lastname: Nielsen
authors.forename: W M
authors.initials: WM
authors.lastname: Whalen
authors.forename: M
authors.initials: M
authors.lastname: Meltz
authors.forename: D
authors.initials: D
authors.lastname: Phillips
authors.forename: P F
authors.initials: PF
authors.lastname: Thadieo
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.forename: D S
authors.initials: DS
authors.lastname: Chapin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000201:enzymology*; D005260:Female; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D020889:Rolipram; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012110:Reserpine; D020889:Rolipram; D002118:Calcium