Thiazolo[5,4-d]pyrimidine derivatives as amplifiers of phleomycin against Escherichia coli

Abstract

The acetylation of 5-amino-6-methylpyrimidine-2,4-dithione (1; R = H) followed by cyclo-dehydration gave 2,7-dimethylthiazolo[5,4-d] pyrimidine-5-thione (2; R = Me) which underwent S-alkylation by methyl iodide, 2-chloroacetamide, etc, to afford the corresponding 5-alkylthio derivatives (4a-c). Treatment of the same substrate with carbon disulphide provided 7-methyl-thiazolo[5,4-d]pyrimidine-2,5-dithione (6) and thence the corresponding 2,5-bisalkylthio derivatives (4d-g). Similar reactions with 5-amino-6-mercapto-2-methylpyrimidine-4- thione(5; R1 = Me, R2 = SH, R3 = H) gave 7-alkylthio-2,5- dimethylthiazolo[5,4-d]pyrimidines (4h-p) and 2,7-bis-alkylthio-5- methylthiazolo[5,4-d]pyrimidines [(4q) and (4r)]. Two 2-alkylthio-7- methoxythiazolo-[5,4-d]pyrimidines, (4s) and (4t), were made by similar methods. ��� The foregoing compounds were tested in vitro as amplifiers of phleomycin against E. coli. Some of the more soluble compounds showed activities comparable with those of the best purine amplifiers previously tested.