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 pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones 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.

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.Figure optionsDownload as PowerPoint slide