INHIBITORY EFFECTS ON PLATELET-AGGREGATION AND CYCLIC-AMP PHOSPHODIESTERASE OF AZAINDOLIZINE-TYPE COMPOUNDS - STRUCTURE-ACTIVITY-RELATIONSHIPS AND MOLECULAR MODELING

This paper deals with the synthesis and biological activities of aryl- 2 imidazo[1,2-a]pyridines and pyrimidines. These compounds are valued as inhibitors of cyclic AMP phosphodiesterase (PDE) derived from beef heart and as inhibitors of human platelet aggregation. The most attrac tive in this series, compounds 13a and 15a, are ten times more potent than aspirin on arachidonic acid induced platelet aggregation. They al so exhibit significant activity as inhibitors of phosphodiesterase. An alysis of these azaindolizine-type compounds by molecular modelling te chniques suggests spatial and electronic similarities with other class es of PDE inhibitors.