Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors.

Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds. In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and pyrazolopyrimi-dinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones (e.g., 30) were also shown to be potent and selective PDE inhibitor scaffolds with in vivo activity. SAR trends were elucidated for sulfonamide derivatives with generality across different scaffolds.