NEW PRODRUG APPROACH FOR AMINO-ACIDS AND AMINO-ACID-LIKE DRUGS

A series of disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (TH TT) derivatives 4a-g were prepared and found to be promising prodrugs for amino acids and similar compounds. The pH profile for the degradat ion of the THTT derivatives in aqueous buffer solutions was determined using HPLC and was accounted for in terms of specific base-catalyzed reactions. The compounds, however, showed high acid stability. Enzymat ic hydrolysis (human serum)of th derivatives offered an advantageous r ange of t(1/2) values, which may be useful in controlling the onset an d the duration of action of drugs.