Design of orally active iron chelators.
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.
Hider
R C
RC
Department of Pharmacy, King's College London, University of London, UK.
Choudhury
R
R
Rai
B L
BL
Dehkordi
L S
LS
Singh
S
S
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
D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D011355:Prodrugs; D011728:Pyridones