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Synthesis of labeled BCX‐4208, a potent inhibitor of purine nucleoside phosphorylase
Author(s) -
Kamath Vivekanand P.,
JuarezBrambila Jesus J.,
Morris Philip E.
Publication year - 2009
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.24
Subject(s) - oxocarbenium , purine nucleoside phosphorylase , chemistry , stereochemistry , enzyme , nucleoside , purine , biochemistry , catalysis , nucleophile
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.