Synthesis of labeled BCX-4208, a potent inhibitor of purine nucleoside phosphorylase

BCX-4208, a novel inhibitor of the enzyme purine nucleoside phosphorylase, mimics the charged ribosyl oxocarbenium ion formed during the transition state of the enzyme-catalyzed C-N bond cleavage of nucleosides. A slow-onset, tight-binding inhibitor with a Ki(*) of 16 +/- 1.4 pM, BCX-4208 is one of...

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Bibliographic Details
Published inDrug testing and analysis Vol. 1; no. 3; p. 125
Main Authors Kamath, Vivekanand P, Juarez-Brambila, Jesus J, Morris, Jr, Philip E
Format Journal Article
LanguageEnglish
Published England 01.03.2009
Subjects
Catalysis - drug effects
Chromatography, High Pressure Liquid - methods
Chromatography, Thin Layer - methods
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Purine-Nucleoside Phosphorylase - antagonists & inhibitors
Pyrimidinones - chemical synthesis
Pyrimidinones - pharmacology
Pyrrolidines - chemical synthesis
Pyrrolidines - pharmacology
Static Electricity
Tandem Mass Spectrometry
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Summary:BCX-4208, a novel inhibitor of the enzyme purine nucleoside phosphorylase, mimics the charged ribosyl oxocarbenium ion formed during the transition state of the enzyme-catalyzed C-N bond cleavage of nucleosides. A slow-onset, tight-binding inhibitor with a Ki(*) of 16 +/- 1.4 pM, BCX-4208 is one of the most potent inhibitors known for the enzyme. In support of our BCX-4208 clinical program, a mass spectrometric assay has been developed that required labeled BCX-4208 as an internal standard. The synthesis of [(2)H](2)-BCX-4208 and [(13)C]-BCX-4208 is described in this report.
ISSN:1942-7611
DOI:10.1002/dta.24