- Systematic comparison of the mono-, dimethyl-and trimethyl 3-hydroxy-4(1H)-pyridones-Attempted optimization of the orally active iron chelator, deferiprone
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A range of close analogues of deferiprone have been synthesised. The group includes mono-, di-and trimethyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe3+ values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NHcontaining 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.
- Xie, Yuan-Yuan,Lu, Zidong,Kong, Xiao-Le,Zhou, Tao,Bansal, Sukhi,Hider, Robert
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p. 132 - 140
(2016/04/05)
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- 1,4-Dihydro-4-oxo-pyridylacetamido cephalosporins and their utilization as medicinal agents for combating bacterial infections
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Cephem derivatives of the formula STR1 wherein Z is 1,4-dihydro-4-oxo-1-pyridyl or the corresponding group substituted by one or more of alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, OH, F, Cl, Br, I, NO2 and NH2 ; and R is H, --OCOCH3 or -S-Het, wherein Het is 3-methyl-1,2,4-thiadiazolyl-5, 5-methyl-1,3,4-oxadiazolyl-2, 5-hydroxymethyl-1,3,4-oxadiazolyl-2, 5-methyl-1,3,4-thiadiazolyl-2, 5-hydroxymethyl-1,3,4-thiadiazolyl-2, tetrazolyl-5, 1-methyltetrazolyl-5, 1,2,3-triazolyl-4, 4-methyl-oxazolyl-2 or 1-oxidopyridinio-2, and the readily cleavable esters thereof and the physiologically acceptable salts thereof, possess anti-bacterial activity and can be prepared by reacting a 3-CH2 R-7-amino-3-cephem-4-carboxylic acid or a functional derivative thereof with a pyridone acetic acid of the formula Z-CH2 -COOH or a functional derivative thereof.
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