Preparation of 2-Amino-4(3H)-oxopyrimido[5,4-b][l,4]thiazines (5-Thiapterins1) and Their Evaluation as Cofactors for Phenylalanine Hydroxylase

Robert N. Henrie, Robert A. Lazarus, Stephen J. Benkovic

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)559-563
Number of pages5
JournalJournal of Medicinal Chemistry
Volume26
Issue number4
DOIs
StatePublished - Apr 1983

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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