title: Synthesis and biodistribution of [4-14C]-5-bromo-6-methoxy-5,6-dihydro-prodrug derivatives of 5-ethyl-2'-deoxyuridine.
abstract: The radiochemical syntheses of the [4-14C]-(-)-trans-(5S,6S)-5-bromo-5- ethyl-6-methoxy-5,6-dihydro-2'-deoxyuridine [2,(5S,6S)-BMEDU] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6- methoxy-5,6-dihydro-2'-deoxyuridine [3,(5R,6R)-BMEDU] are reported. These BMEDU diastereomers were synthesized in 21 and 25% radiochemical yield, respectively, by direct addition of methyl hypobromite to the 5,6-olefinic bond of [4-14C]-5-ethyl-2'-deoxyuridine (EDU). The biodistributions of [4-14C]-labelled diastereomers of 2 and 3, and EDU were determined in male Balb-C mice. The uptake of radioactivity in brain after injection of [4-14C]-BMEDU diastereomers of 2 and 3 was not significantly different than that of [4-14C]-EDU (P > 0.05). However, clearance of radioactivity from blood was substantially faster after injection of [4-14C]-EDU relative to the [4-14C]-BMEDU diastereomers. Liver samples, obtained after injection of the [4-14C]-BMEDU diastereomers, showed a higher percentage uptake of the injected dose per gram of tissue relative to liver samples obtained after injection of [4-14C]-EDU.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Cheraghali
authors.forename: K W
authors.initials: KW
authors.lastname: Morin
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: E E
authors.initials: EE
authors.lastname: Knaus
authors.forename: L I
authors.initials: LI
authors.lastname: Wiebe
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011854:Radiochemistry / Q000379:methods; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D011355:Prodrugs; C087238:5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2'-deoxyuridine; C022811:edoxudin; D003857:Deoxyuridine