INVESTIGATIONS ON THE BIOTRANSFORMATION O F THE IMMUNOSTIMULATOR 3-(2-MERCAPTOETHYL)QUINAZOLINE-2,4(1H,3H)-DIONE (AWD-100-041)

3-(2-Mercaptoethyl)quinazoline-2,4(1 H,3 H)-dione (1; AWD 100-041) is a substance with immunomodulating and immunorestorative activity. Afte r p.o. administration in male Wistar rats at least 7 metabolites are f ormed and excreted in urine and faeces. The compounds were isolated an d identified on the basis of UV and mass spectra. They are S-methylate d structures in which sulfoxidation and ring-hydroxylation have been t aken place. Four metabolites are also present as sulfate or glucuronid e conjugates. The quantity ratio of the phase I to phase II metabolite s amounts to 4:1. In the isolated perfused rat liver and rat hepatocyt e culture 6 and 5 of the in vivo identified compounds are formed. The sequence of the metabolic pathways could be confirmed by in vitro expe riments in which the incubation of synthetically prepared metabolites and the identification of generated biotransformation products were pe rformed. In the lymphocyte and myeloma cell culture solely the disulfi de of 1 is formed. After incubation of the S-methyl compound metabolit es originate detectable also in vivo. Regarding the main ways of metab olism firstly 1 is attacked by methyltransferases forming the initial metabolite. After that oxidative processes take place leading to the f ormation of sulfoxides, sulfones as well as ring-hydroxylated compound s. A part of the ring-hydroxylated metabolites are conjugated.