Abatract. A QSAR study has been performed on a series of Substituted Pyrido[3,2b]pyrazinones as Potent and Selective PDE-5 Inhibitors. The compounds in the selected series were characterized by spatial, molecular and electrotopological descriptors using QSAR module of molecular design suite (V-Life MDS^TM 3.5). Correlations between inhibitory activities and calculated predictor variables were established through partial least square regression (stepwise forward) method. The generated QSAR models reveal that the topology of the molecules is crucially influence the desired inhibitory activity of Pyrido[3,2b]pyrazinones.  Present QSAR studies authenticate the dependency of inhibitory activity of the selected series on structural properties. Both PDE-5 and PDE-6 activities can be well defined by generated QSAR models, for PDE-5 activity the best model shows 90 % correlation and 91% correlation for PDE-6 activity which, explain reliability of the model. However other terms like cross correlated regression coefficients (Q²) 0.5959 and 0.6342 respectively for PDE-5 and PDE-6 activities, also validate the model significance. The study imply that the PDE inhibition can be augmented primarily by increasing molecular refractivity and number of carbons connected to the aromatic rings and single bonds and by decreasing number of carbons connected to the double bonds. 


KEY WORDS: PDE-5 Inhibitors; Pyrido[3,2b]pyrazinones; molecular design suite (MDS); quantitative structure activity relationship (QSAR).