Prodrugs of 9-Benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine：Potent Interferon Inducing Agents in Monkeys

In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM295072), a potent interferon (IFN) inducing agent, we synthesized prodrugs of it by utilizing the hydroxy groups at the C(2)-side chain and/or the C(8)-position. The carbonate prodrug at the C(8)-posi...

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Published inChemical & Pharmaceutical Bulletin Vol. 52; no. 4; pp. 466 - 469
Main Authors Ayumu KURIMOTO, Masanori TOBE, Haruhisa OGITA, Tetsuhiro OGINO, Haruo TAKAKU, Shinji ICHII, Hajime KAWAKAMI, Yoshiaki ISOBE
Format Journal Article
LanguageJapanese
Published Pharmaceutical Society of Japan 2004
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Summary:In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM295072), a potent interferon (IFN) inducing agent, we synthesized prodrugs of it by utilizing the hydroxy groups at the C(2)-side chain and/or the C(8)-position. The carbonate prodrug at the C(8)-position was more effective than that at the C(2)-side chain for oral absorption in rats. Among the compounds prepared, compound 6 demonstrated the most preferable prodrug properties, and the maximum plasma concentration of 6 was approximately 4-fold higher than that of SM-295072. Furthermore, compound 6 was dose-dependently absorbed in monkeys by oral administration, and exhibited a potent IFN-inducting activity that correlated well with its plasma drug concentration.
ISSN:0009-2363
1347-5223