A β-fluoroamine inhibitor of purine nucleoside phosphorylase

Jennifer M. Mason, Andrew S. Murkin, Lei Li, Vern L. Schramm, Graeme J. Gainsford, Brian W. Skelton

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The potent immucillin purine nucleoside phosphorylase (PNP) inhibitors F-DADMe-ImmH [(3S,4S)-3], and [(3R,4R)-3] are synthesized in seven steps. Cycloaddition to a fluoroalkene and an enzymic resolution are the key features of the construction of the fluoropyrrolidines 11, from which the immucillins are assembled by use of a three-component Mannich reaction. Slow-onset binding constants (Ki*) for [(3S,4S)-3] and [(3R,4R)-3] with human PNP are 0.032 and 1.82 nM, respectively. F-DADMe-ImmH [(3S,4S)-3] exhibits oral availability in mice at doses as low as 0.2 mg/kg.

Original languageEnglish (US)
Pages (from-to)5880-5884
Number of pages5
JournalJournal of Medicinal Chemistry
Volume51
Issue number18
DOIs
StatePublished - Sep 25 2008

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Purine-Nucleoside Phosphorylase
Cycloaddition Reaction

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Mason, J. M., Murkin, A. S., Li, L., Schramm, V. L., Gainsford, G. J., & Skelton, B. W. (2008). A β-fluoroamine inhibitor of purine nucleoside phosphorylase. Journal of Medicinal Chemistry, 51(18), 5880-5884. https://doi.org/10.1021/jm800792b

A β-fluoroamine inhibitor of purine nucleoside phosphorylase. / Mason, Jennifer M.; Murkin, Andrew S.; Li, Lei; Schramm, Vern L.; Gainsford, Graeme J.; Skelton, Brian W.

In: Journal of Medicinal Chemistry, Vol. 51, No. 18, 25.09.2008, p. 5880-5884.

Research output: Contribution to journalArticle

Mason, JM, Murkin, AS, Li, L, Schramm, VL, Gainsford, GJ & Skelton, BW 2008, 'A β-fluoroamine inhibitor of purine nucleoside phosphorylase', Journal of Medicinal Chemistry, vol. 51, no. 18, pp. 5880-5884. https://doi.org/10.1021/jm800792b
Mason, Jennifer M. ; Murkin, Andrew S. ; Li, Lei ; Schramm, Vern L. ; Gainsford, Graeme J. ; Skelton, Brian W. / A β-fluoroamine inhibitor of purine nucleoside phosphorylase. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 18. pp. 5880-5884.
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