A comparative study of binding affinities for 6,7-dimethoxy-4-pyrrolidylquinazolines as phosphodiesterase 10A inhibitors using the linear interaction energy method.

The linear interaction energy (LIE) method was used to estimate the free energies of binding for a set of 27 pyrrolidylquinazoline derivatives as phosphodiesterase 10A inhibitors. Twenty-six X-ray crystal structures of phosphodiesterase 10A and two sampling methods, minimization and Hybrid Monte Carlo, were used to assess the affinity models based on the linear interaction energies. The best model was obtained based on the parameters α=0.