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 $\hbox{K}_{\rm i}^{*}$ of 16 ± 1.4 p M, 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. Copyright © 2009 John Wiley & Sons, Ltd.