새로운 5-치환 Uracil 유도체의 합성 및 생물활성

Synthesis and Biological Activities of New 5-Substituted Uracil Derivatives

Six novel 5-substituted-1-[2-(3-methoxy-2-hydroxyphenyl)-l-methoxyethyl]uracils 2a-f were prepared by condensation of 2,4-bis(trimethylsilyloxy)-5-substituted uracils with 2,7-dimethoxy-2,3-dihydrobenzofuran (9) in the presence of Lewis acid. The 2,3-dihydrobenzofuran derivative 9 was obtained by intramolecular acetalization of 2-acetoxy-3-methoxyphenyl acetaldehyde (8) which was synthesized by oxidative cleavage of 1-allyl-2-acetoxy-3-methoxybenzene (7) using osmium tetroxide followed by NaIO4. Compounds 2a-f were evaluated for in vitro antiviral activity against HSV-1, HSV-2 and HRV. None of these compounds showed activity with ID50) values up to 100 mcg/ml except for 5-chlorouracil derivative 2d which exhibited antiviral activity against HSV-1 with ED50) 30 mcg/ml. In the antitumor activity against L1210 and P388 leukemia cell lines, 2d showed activity with ID50 values of 14 mcg/ml and 11.6 mcg/ml, and 2c with ID50 values of 22.9 mcg/ml and 8.8 mcg/ml, respectively.