Synthesis and evaluation of carbamate prodrugs of a phenolic compound |
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Authors: | Igarashi Yasushi Yanagisawa Erika Ohshima Toshihiro Takeda Shuichi Aburada Masaki Miyamoto Ken-ichi |
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Institution: | R&D Division, Tsumura & Co., Ibaraki, Japan. igarashi_yasushi@mail.tsumura.co.jp |
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Abstract: | A series of carbamates of the phenolic compound 1 were prepared and evaluated in vivo as its prodrug. Each carbamate was orally administered to rats, and plasma concentrations of the parent compound 1 were measured with the passage of time. We judged which carbamate was suitable for the prodrug of 1 from both the AUC value of 1 and absence of the carbamate in plasma. The AUC value of 1 after oral administration of 2b was approximately 40-fold higher than that for an administration of 1, and the bioconversion from 2b to 1 was excellent. As a whole, di-substituted carbamates resulted in higher plasma concentrations of 1 than did mono-substituted ones. However di-substituted carbamates were almost always detected in plasma. As a result, we found that the ethycarbamoyl derivative 2b demonstrates the best prodrug property in this series. |
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