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 journalArticlepeer-review

47 Scopus citations


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
Issue number18
StatePublished - Sep 25 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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