Synthesis and platelet aggregation inhibitory activity of 4,5-bis(substituted)-1,2,3-thiadiazoles.
Routine screening of compounds for inhibition of collagen-induced platelet aggregation in vitro revealed 4,5-bis-(4-methoxyphenyl)-1,2,3-thiadiazole (2) was active and it represents the first example of a 1,2,3-thiadiazole with possible antithrombotic activity. In order to develop a structure-activity relationship for this heterocycle, a number of new 4(5)-mono- and -disubstituted 1,2,3-thiadiazoles were synthesized. These were tested in our screen and a number of additional active compounds were found. The most active compounds (2, 5a, 5b, and 6c) were those in which the heterocycle was substituted with benzene rings possessing para electron-donating groups.
D003094:Collagen / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D013830:Thiadiazoles; D003094:Collagen