title: Design and synthesis of novel pegylated iron chelators with decreased metabolic rate.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Polymer Science & Engineering, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Junpei
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Pharmaceutical Science, King's College London, SE1 9NH London, UK.
authors.forename: Zidong
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Institute of Pharmaceutical Science, King's College London, SE1 9NH London, UK.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Kong
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 310053 Hangzhou, China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Polymer Science & Engineering, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pharmaceutical Science, King's College London, SE1 9NH London, UK.
authors.forename: Sukhvinder S
authors.initials: SS
authors.lastname: Bansal
authors.affiliation: Institute of Pharmaceutical Science, King's College London, SE1 9NH London, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Abbate
authors.affiliation: Institute of Pharmaceutical Science, King's College London, SE1 9NH London, UK.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
mesh_terms: D000077543:Deferiprone; D015195:Drug Design; D006801:Humans; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D011092:Polyethylene Glycols