TABLE 2

IC₅₀ and 1/2 EC₅₀ values for PDE5 inhibitor analogs

Structures of analogs are shown with differences encircled. IC₅₀ values were determined by adding PDE5 (10 μl; 0.11 nM final concentration) to PDE assay reaction mixture containing increasing concentrations of the analogs. PDE activity was determined in a 15-min incubation as described under Materials and Methods using 0.4 μM (final concentration) [³H]cGMP as substrate. EC₅₀ values were determined by adding increasing concentrations of unlabeled inhibitor analog to 2 ml of binding reaction mixture that contained 0.5 nM [³H]vardenafil. Filtration was performed as outlined under Materials and Methods. Student's t tests indicate that IC₅₀ and K_D values for methyl-sildenafil were significantly different (p < 0.05) from the IC₅₀ and K_D values for demethyl-vardenafil, vardenafil, and sildenafil.