| Summary: | 碩士 === 中國醫藥大學 === 藥物化學研究所碩士班 === 94 === 5-Methyl-2-(3-methoxyphenyl)-1,8-naphthyridine (6a) and 6-methyl-2-(3-methoxyphenyl)-1,8-naphthyridine (6b) have been synthesized and shown potent cytotoxicity. However, during the undergoing in vivo tests and other preclinical studies, their limited water solubility complicated the issues of IV preparation and oral formulation. To simplify these issues several carbamate and amine derivatives of 6a were synthesized and their cytotoxicity were examined. Strangely, attempted to introduce a bromo group into the benzylic carbon of 6a or 6b by treatment with NBS or DDH in the presence of AIBN or benzoyl peroxide was failed. In an effort to solve the brominated problem of 6a or 6b, we constructed the 1,8-naphthyridine by O-alkylation on the 4 position of 1,8-naphthyridin-4-one. But the bromination of them was also failure. Nevertheless, in this thesis, we provided the new approach to synthesis the carbamate and amine prodrugs of 1,8- naphthyridin-4-one. The single dose of these carbamate and amine derivatives for pharmacokinetic study are on progress.
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