Synthesis and in vitro antimicrobial activity of 5-substituted 2H-1,3,5-thiadiazine-2,4(3H)-diones

A series of 6-substituted 2H-1,3,5-thiadiazine-2,4(3H)-diones (1a-m) was prepared by treatment of alkyl, aryl, and heterocyclic primary thioamides with phenoxycarbonyl isocyanate to give N-(phenoxycarbonyl)-N'-thioacylureas, which gave 1 upon heating in refluxing xylene solution or upon treatment with aqueous sodium carbonate solution followed by acidification. 1H NMR and infrared spectral evidence indicates that the 6-alkyl derivatives 1a,b,l,m exist predominately in the exocyclic alkylidene tautomeric form. The major product obtained from alkaline and acid hydrolysis of the 6-phenyl derivative 1c was found to be benzoic acid and benzoylurea, respectively. The majority of compounds 1a-m exhibited in vitro antifungal activity against Candida albicans and Trichophyton mentagrophytes. Several derivatives, 1b-d,h,j, displayed minimum inhibitory concentration values below 2 micrograms/mL against Trichophyton mentagrophytes. Four derivatives, 1c,e,g,h, inhibited the growth of Seratia marcesens, Staphylococcus aureus, and Staphylococcus epidermis in an in vitro sensitivity disk assay. 2-Furyl derivative 1h displayed antileukemic activity against P-388 lymphocytic leukemia.