Effects of novel catechol ether imidazolidinones on calcium-independent phosphodiesterase activity, [3H]rolipram binding, and reserpine-induced hypothermia in mice

A series of new catechol ether imidazolidinones incorporating structural features of rolipram and Ro 20‐1724 were synthesized as inhibitors of the calcium‐independent phosphodiesterase (IPDE) from rat cerebral cortex. Several compounds were found to be more potent than rolipram as IPDE inhibitors; all of the compounds studied were more potent than Ro 20‐1724. The new imidazolidinones also showed affinity for the [3H]rolipram binding site in mouse brain membranes and reversed reserpine‐induced hypothermia in mice at relatively low doses. In vitro, the potency of these compounds as IPDE inhibitors did not correlate with their affinity for the [3H]rolipram binding site. Reversal of reserpine hypothermia by the imidazolidinones (“antidepressant effect”) could not be linked definitively to either in vitro activity.