Substituent effects on desferrithiocin and desferrithiocin analogue iron-clearing and toxicity profiles

RJ Bergeron, J Wiegand, N Bharti…

Index: Bergeron, Raymond J.; Wiegand, Jan; Bharti, Neelam; McManis, James S. Journal of Medicinal Chemistry, 2012 , vol. 55, # 16 p. 7090 - 7103,14

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Citation Number: 6

Abstract

Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure–activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to ...