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The Design of Orally Active Iron Chelators

Abstract: It is now generally accepted that it is not possible to design iron(III)‐selective hexadentate chelators with high oral bioavailability. In order to achieve suitable levels of oral activity for the treatment of systemic iron overload either tridentate or bidentate molecules need to be investigated. There are a number of such molecules in clinical practice, including hydroxypyridin‐4‐ones, desferrithiocin analogues and bis‐hydroxyphenyltriazoles. The underlying chemistry of each group is described, together with an indication of the distribution properties, redox cycling activity, and iron scavenging activity.