Comparative molecular field analysis (CoMFA) for phosphodiesterase (PDE) IV inhibitors

A comparative molecular field analysis (CoMFA) for phosphodiesterase (PDE) IV inhibitors has been performed to correlate their chemical structures with their observed biological activity. In this study, CoMFA model based on docking mode for active site of PDE IV can describe the relative change in magnitude of the steric and electrostatic fields as a function of the compounds. Pyridine N-oxide and pyridine group of each compound are aligned toward the metal ion in S2-sub pocket of PDE IV. The study provided a statistically valid model with good correlation and predictive power, and consequently we identified some key features that may be used to design new derivatives.