Prodrugs of 9-Benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine

In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM-295072), 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)-pos...

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Bibliographic Details
Published inChemical & pharmaceutical bulletin Vol. 52; no. 4; p. 466
Main Authors Kurimoto, Ayumu, Tobe, Masanori, Ogita, Haruhisa, Ogino, Tetsuhiro, Takaku, Haruo, Ichii, Shinji, Kawakami, Hajime, Isobe, Yoshiaki
Format Journal Article
LanguageEnglish
Published Tokyo Japan Science and Technology Agency 01.04.2004
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Summary:In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM-295072), 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