title: Design of orally active iron chelators.
abstract: Three parameters which are critical for the development of non-toxic orally active iron chelators are identified: bioavailability, selectivity for iron (III) and distribution and toxicity. Each is discussed in detail. Arguments are presented for the use of bi- and tridentate ligands as opposed to hexadentate ligands. The discussion leads to the identification of 3-hydroxpyridin-4-ones as compounds with a unique potential for iron chelation under clinical conditions. The prodrug concept utilising efficient liver first-pass kinetics is introduced.
authors.affiliation: Department of Pharmacy, King's College London, University of London, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Hider
authors.forename: R
authors.initials: R
authors.lastname: Choudhury
authors.forename: B L
authors.initials: BL
authors.lastname: Rai
authors.forename: L S
authors.initials: LS
authors.lastname: Dehkordi
authors.forename: S
authors.initials: S
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015195:Drug Design; D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D011355:Prodrugs; D011728:Pyridones / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D011355:Prodrugs; D011728:Pyridones