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 Benkovic

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 - Jan 1 1983

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Thiazines
Phenylalanine Hydroxylase
Lactams
Guanidine
Oxides
Amines
Oxygen
Acids
Liver
6-methyltetrahydropterin
sapropterin
triethyloxonium tetrafluoroborate

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

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Preparation of 2-Amino-4(3H)-oxopyrimido[5,4-b][l,4]thiazines (5-Thiapterins1) and Their Evaluation as Cofactors for Phenylalanine Hydroxylase. / Henrie, Robert N.; Lazarus, Robert A.; Benkovic, Stephen.

In: Journal of Medicinal Chemistry, Vol. 26, No. 4, 01.01.1983, p. 559-563.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation of 2-Amino-4(3H)-oxopyrimido[5,4-b][l,4]thiazines (5-Thiapterins1) and Their Evaluation as Cofactors for Phenylalanine Hydroxylase

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AU - Lazarus, Robert A.

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AB - 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.

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