A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.