title: Synthesis and pharmacokinetic and pharmacodynamic evaluation of the forodesine HCl analog BCX-3040.
abstract: Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP) and is currently in clinical trials for the treatment of leukemia and lymphoma. Animal models indicated that forodesine HCl would have low oral bioavailability in humans and it was initially developed as an intravenous formulation. We were interested in identifying analogs of forodesine HCl with improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl.
authors.affiliation: BioCryst Pharmaceuticals Inc., Birmingham, Alabama 35244, USA.
authors.forename: Hollis S
authors.initials: HS
authors.lastname: Kezar
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilpatrick
authors.forename: Deborah
authors.initials: D
authors.lastname: Phillips
authors.forename: Debbie
authors.initials: D
authors.lastname: Kellogg
authors.forename: Jianwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Philip E
authors.initials: PE
authors.lastname: Morris
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006595:Hexosamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D006595:Hexosamines; C012325:forosamine; D011683:Purine-Nucleoside Phosphorylase