Abstract
We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications. Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally. Several modifications are reported here which achieved more than twofold improvement in exposure. A compound with significant improvement in oral efficacy was also obtained.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Catalytic Domain
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Cytosine / administration & dosage
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Cytosine / analogs & derivatives*
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Cytosine / chemistry
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Cytosine / pharmacology
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Enzyme Activation / drug effects
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Inhibitory Concentration 50
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Models, Animal
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Models, Molecular
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Molecular Structure
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Rats
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Xanthine Oxidase / antagonists & inhibitors*
Substances
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Enzyme Inhibitors
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isocytosine
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Cytosine
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Xanthine Oxidase