8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases

Gary B. Evans, Richard H. Furneaux, Graeme J. Gainsford, John C. Hanson, Gregory A. Kicska, Antony A. Sauve, Vern L. Schramm, Peter C. Tyler

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54 Scopus citations

Abstract

The 8-aza-immucillins (8-aza-9-deazapurines linked from C9 to C1 of 1,4-dideoxy-1,4-iminoribitol) have been designed as transition-state analogues of the reactions catalyzed by purine nucleoside phosphorylase and nucleoside hydrolases. Syntheses of the 8-aza-immucillin analogues of inosine and adenosine are described. They are powerful inhibitors of the target enzymes with equilibrium dissociation constants as low as 42 pM.

Original languageEnglish (US)
Pages (from-to)155-160
Number of pages6
JournalJournal of Medicinal Chemistry
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 2 2003

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Evans, G. B., Furneaux, R. H., Gainsford, G. J., Hanson, J. C., Kicska, G. A., Sauve, A. A., ... Tyler, P. C. (2003). 8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases. Journal of Medicinal Chemistry, 46(1), 155-160. https://doi.org/10.1021/jm0203332