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 inhibitors of human platelet aggregation. Appropriately substituted compounds were found to fully inhibit platelet aggregation, and anhydro-(6-ethyl-8-isopentyl-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 aggregation and this might be due to its ability to act as a latent acylation agent.
Hellberg
M
M
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA. mark.hellberg@alconlabs.com
Stubbins
J F
JF
Glennon
R A
RA
D001792:Blood Platelets / Q000378:metabolism; D002850:Chromatography, Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D014970:Xanthines