Imidazotriazinone inhibitors of the Ca2+-calmodulin sensitive phosphodiesterase (PDE I)

Hybrid structural analogs 1 of the PDE V and PDE III inhibitors, zaprinast, milrinone, and CI-930 were prepared to identify dual PDE inhibitors. The SAR study led unexpectedly to the identification of WIN 61691 (8d), a potent inhibitor of PDE I (IC50 = 85 nM). A potent and selective inhibitor of PDE I would be a useful tool to elucidate the physiologic function of PDE I and other PDE isozymes in biological systems.