title: Synthesis and biological evaluation of naphthyldesferrithiocin iron chelators.
abstract: The synthesis and iron-clearing properties of the naphthyldesferrithiocins 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4R)-carboxylic acid, 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4S)-carboxylic acid, 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4R)-carboxylic acid, and 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4S)-carboxylic acid are described. While the bile duct-cannulated rat model clearly demonstrates that the 3'-hydroxynaphthyl-2'-yl compounds are orally active iron-clearing agents and the corresponding 2'-hydroxynaphthyl-1'-yl compounds are not, in the primate model none of the benz-fused desazadesferrithiocin analogues are active. Oral versus subcutaneous administration of these ligands strongly suggests that metabolism is a key issue in their iron-clearing properties and that these benz-fused desferrithiocins are not good candidates for orally active iron-clearing drugs.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, 32610, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Bergeron
authors.forename: J
authors.initials: J
authors.lastname: Wiegand
authors.forename: M
authors.initials: M
authors.lastname: Wollenweber
authors.forename: J S
authors.initials: JS
authors.lastname: McManis
authors.forename: S E
authors.initials: SE
authors.lastname: Algee
authors.forename: K
authors.initials: K
authors.lastname: Ratliff-Thompson
mesh_terms: D000818:Animals; D002428:Cebus; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000138:chemical synthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D004095:Dihydropyridines; D007502:Iron Chelating Agents; D013844:Thiazoles; D007501:Iron; C050223:desferrithiocin