Novel inhibitors of human type II cAMP-specific phosphodiesterase isozyme with the cyclic 4',5'-imidazolone as a novel core structure. New cAMP specific phosphodiesterase (PDE) inhibitors (type II PDE inhibitors) with the novel cyclic 4',5'-imidazolone as a novel core structure were designed and synthesized. Among the compounds, 2-adamantyl-5-(2'-pyrrolidinoylamino)methylimidazolone (11f) showed potent inhibitory activity in vitro, with Ki value of 3.2 x 10(-8) M. When used in combination with a phosphodiesterase-4 inhibitor Ro 20-1724, they significantly potentiated the elevation of cAMP levels in differentiated HL-60 cells, which suggests that the new cyclic 4',5'-imidazolone will be a promising scaffold for new type II PDE inhibitors.