Lead optimization of isocytosine-derived xanthine oxidase inhibitors.
Bioorganic & Medicinal Chemistry Letters(2013)
摘要
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.
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关键词
XOR,XO,PK,AUC,XDH,ip,po,SAR,UA,sUA
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