New prodrug approach for amino acids and amino-acid-like drugs

Article abstract of DOI:10.1016/0223-5234(96)80450-8

A series of disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives 4a-g were prepared and found to be promising prodrugs for amino acids and similar compounds. The pH profile for the degradation 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. Enzymatic hydrolysis (human serum) of the derivatives offered an advantageous range of t( 1/2 ) values, which may be useful in controlling the onset and the duration of action of drugs.