title: 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 [(2)H](2)-BCX-4208 and [(13)C]-BCX-4208 is described in this report.
authors.affiliation: BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, Alabama 35244, USA. vkamath@biocryst.com
authors.forename: Vivekanand P
authors.initials: VP
authors.lastname: Kamath
authors.forename: Jesus J
authors.initials: JJ
authors.lastname: Juarez-Brambila
authors.forename: Philip E
authors.initials: PE
authors.lastname: Morris
mesh_terms: D002384:Catalysis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D055672:Static Electricity; D053719:Tandem Mass Spectrometry
chemical_list: D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D011759:Pyrrolidines; D011683:Purine-Nucleoside Phosphorylase; C032519:pyrrolidine