TRICYCLIC THEOPHYLLINE DERIVATIVES WITH HIGH WATER-SOLUBILITY - STRUCTURE-ACTIVITY-RELATIONSHIPS AT ADENOSINE RECEPTORS, PHOSPHODIESTERASES, AND BENZODIAZEPINE BINDING-SITES

A series of tricyclic, highly water-soluble theophylline derivatives ( pyrimido[2,1-f]-theophyllines) containing a basic side chain was inves tigated in rat brain A(1)- and A(2) adenosine receptor binding assays, phosphodiesterase assays, and benzodiazepine binding studies. Among t he new compounds adenosine receptor antagonists with affinities in the same range as the parent compound theophylline were identified. In ad dition, some compounds were selective for the A(1) adenosine receptor subtype. The compounds generally exhibited lower inhibitory activity a t brain phosphodiesterases than the parent theophylline. Two compounds were found to show an about 10-fold affinity for benzodiazepine bindi ng sites compared with caffeine and theophylline.