A preliminary investigation of mesoionic xanthine analogues as inhibitors of platelet aggregation

A series of mesoionic xanthines (e.g, mesoionic thiazolopyrimidines, 3, and thiadiazolopyrimidines, 5) and related analogues were examined as inhibito rs of human platelet aggregation. Appropriately substituted compounds were found to fully inhibit platelet aggregation, and anhydro-(6-ethyl-8-isopent yl-7-oxo-5-hydroxy-1,3,4-thiadiazolo[3,2-a]pyrimidinium hydroxide) (5b) was 40 times more potent than the structurally related xanthine theophylline ( 1). Gel filtration studies suggest that compound 5b irreversibly inhibits a ggregation and this might be due to its ability to act as a latent acylatio n agent. (C) 2000 Elsevier Science Ltd. All rights reserved.