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논문 기본 정보

자료유형
학술저널
저자정보
Kim, Jack-C. (Department of Chemistry, College of Natural Science, Pusan National University) Kim, Ji-A (Department of Chemistry, College of Natural Science, Pusan National University) Park, Jin-Il (Department of Chemistry, College of Natural Science, Pusan National University) Kim, Si-Hwan (Department of Chemistry, College of Natural Science, Pusan National University) Kim, Seon-Hee (Department of Biochemistry, College of Medicine, Pusan University) Choi, Soon-Kyu (Department of Chemistry, Dong-A University) Park, Won-Woo (Pusan Junior College)
저널정보
대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제20권 제3호
발행연도
1997.1
수록면
253 - 258 (6page)

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Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

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