Transition state analogue inhibitors of protozoan nucleoside hydrolases

Richard H. Furneaux, Vern L. Schramm, Peter C. Tyler

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are potential therapeutic agents for the control of protozoan infections. A series of 1,4-dideoxy-1,4-imino-D-ribitols bearing C- bonded aromatic substituents at C-1 have been synthesized, following carbanion additions to the imine 2, and tested as potential nucleoside hydrolase inhibitors. Nucleoside analogues 8, 11, 14, 17, 20, 24-26, 28 exhibit K(i) values in the range 0.2-22 μM against two representative isozymes of protozoan nucleoside hydrolases. (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)2599-2606
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume7
Issue number11
DOIs
Publication statusPublished - Nov 1 1999

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Keywords

  • Antibiotics
  • Antiparasitics
  • Enzyme inhibitors
  • Nucleosides

ASJC Scopus subject areas

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

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