Synthesis of deuterated‐BCX‐1777, a potent inhibitor of purine nucleoside phosphorylase

Abstract

AbstractBCX‐1777, 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. BCX‐1777 is a slow‐onset, tight‐binding inhibitor with a Ki* of 23 pM and is one of the most potent inhibitors known for the enzyme. In support of our BCX‐1777 program, a mass spectrometric assay has been developed utilizing 5′‐[2H]‐BCX‐1777 as an internal standard. The synthesis of 5′‐[2H]‐BCX‐1777 is described in this report. Copyright © 2002 John Wiley & Sons, Ltd.