Systematic comparison of the mono-, dimethyl- and trimethyl 3-hydroxy-4(1H)-pyridones - Attempted optimization of the orally active iron chelator, deferiprone.
Eur J Med Chem
; 115: 132-40, 2016 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-27014847
ABSTRACT
A range of close analogues of deferiprone have been synthesised. The group includes mono-, di- and tri-methyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe(3+) values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NH-containing hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis.
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Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Quelantes de Ferro
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article