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

Abstract

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 [2H]2-BCX-4208 and [13C]-BCX-4208 is described in this report. Copyright © 2009 John Wiley & Sons, Ltd.