Prodrugs of 9-Benzyl-8-hydroxy-2- (2-hydroxyethylthio) adenine : Potent Interferon Inducing Agents in Monkeys
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概要
- 論文の詳細を見る
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.
- 公益社団法人日本薬学会の論文
- 2004-04-01
著者
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Ochi Takehiro
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ogino T
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Tobe Masanori
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Isobe Y
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Isobe Y
Sumitomo Pharmaceuticals Co. Ltd. Osaka Jpn
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Isobe Yoshiaki
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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TAKAKU Haruo
Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd.
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KURIMOTO Ayumu
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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OGITA Haruhisa
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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OGINO Tetsuhiro
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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TAKAKU Haruo
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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ICHII Shinji
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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KAWAKAMI Hajime
Research Division, Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co. Ltd.
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五十部 穣
Research Center Sumitomo Pharmaceuticals Co. Ltd.
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Ichii Shinji
Research Center Sumitomo Pharmaceuticals Co. Ltd
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Ichii Shinji
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Takaku H
Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.
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Ogino T
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Kurimoto A
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Ogita Haruhisa
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Kawakami H
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Takaku Haruo
Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation
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