Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.
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.
Saccomano
N A
NA
Central Research, Pfizer Inc., Groton, Connecticut 06340.
Vinick
F J
FJ
Koe
B K
BK
Nielsen
J A
JA
Whalen
W M
WM
Meltz
M
M
Phillips
D
D
Thadieo
P F
PF
Jung
S
S
Chapin
D S
DS
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
D000928:Antidepressive Agents; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012110:Reserpine; D020889:Rolipram; D002118:Calcium