Abenzyl 10-formyl-trideazafolic acid (abenzyl 10-formyl-TDAF): An effective inhibitor of glycinamide ribonucleotide transformylase

Dale L. Boger, Nancy Ellen Haynes, Mark S. Warren, Joseph Ramcharan, Ariane E. Marolewski, Paul A. Kitos, Stephen J. Benkovic

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Abstract

The synthesis of N-[7-(2-amino-3,4-dihydro-4-oxo-quinazolin-6-yl)-6-formyl-1-oxo-heptyl]-L -glutamic acid (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enzyme-assembled tight binding inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide fransformylase (AICAR Tfase) is reported. The inhibitor was prepared by a convergent synthesis utilizing the sequential alkylations of acetaldehyde dimethylhydrazone with 6 and 8. The agent exhibited effective inhibition of GAR Tfase (K(i) = 4.5 ± 0.3 μM) and more modest inhibition of AICAR Tfase (K(i) = 42 ± 11 μM).

Original languageEnglish (US)
Pages (from-to)1847-1852
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume5
Issue number9
DOIs
StatePublished - Sep 1 1997

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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