Reaction of diethyl chloromalonate with β-mercapto amines, 9, gave l,4-thiazin-3-ones, 10, which were alkylated exclusively at the lactam oxygen with triethyloxonium tetrafluoroborate and subsequently condensed with guanidine to give the first reported 5-thiapterins, 8. Oxidation of 8 with m-chloroperoxybenzoic acid gave the S-oxides, 12. Both 8 and 12 were found to be good inhibitors of rat liver phenylalanine hydroxylase competitive with 6-methyltetrahydropterin, with 8 exhibiting lower K1's than the corresponding 12. The 8-thiapterin 4 was a much poorer inhibitor.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery