Design and synthesis of novel pegylated iron chelators with decreased metabolic rate

Background: Deferiprone has proved to be a successful iron selective chelator in a range of pathologies. However, its use is limited by rapid phase II metabolism, necessitating the administration of large doses. In an attempt to modify metabolic rate of this class of compounds, a range of pegylated 3-hydroxypyridin-4-ones has been synthesized. Experimental: The synthetic route in which the polyethylene glycol counterparts are introduced to a protected pyran ring involves either a Williamson etherification reaction or direct addition leading to polyethylene glycol-containing precursors. Results & discussion: The introduction of the pegylated substituent was found to lead to a relatively low rate of metabolism for some of the derivatives (6a, 6b, 8a and 8b), offering a possible improvement over deferiprone.