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A CoMFA study of benzo- and benzothienothiadiazines derivatives as phosphodiesterase 7 inhibitors has been carried out in order to determine the factors required for the activity of these compounds and also for the selectivity versus other phosphodiesterase isoenzymes. This methodology is employed to gain clues on the design of new fused thiadiazines with improved activity and selectivity on phosphodiesterase 7. Using the information achieved from the three CoMFA models, new structures have been designed in silico and their inhibitory activity on phosphodiesterase 7 was predicted.