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KMID : 0043319970200030253
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Archives of Pharmacal Research
1997 Volume.20 No. 3 p.253 ~ p.258
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Potential Antitumor -methylene--butyrolactone-bearing nucleic acid bases. 2. synthesis of -[2-(5-substituted uracil-1-yl)ethyl]--methylenetetrahydrofurans
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Kim Jack-C.
Kim Ji-A
Park Jin-Il
Kim Si-Hwan
Kim Seon-Hee
Choi Soon-Kyu
Park Won-Woo
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Abstract
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Ten, heretofore unreported, -methylenetetrahydrofurans (H, F, Cl, Br, I, ,,,, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of -methylene--butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl -(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 (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 ranging from 0.69 to ), 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 .
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KEYWORD
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-Methyl--[2-(5-substituted uracil-1-yl)ethyl)--oxo--methylenetetra-hydrofuran, 1-(5-Dubstituted uracil-1-yl)-3-butanone, Stille coupling reaction, Tris(dibenzylidenacetonyl)bispalladium (Pd2dba), Tri(2-furyl)phosphine, Antitumor activity activity, Reformatsky reaction, Human chronic myelogenous (K-562), Mouse lymphoid neoplasma (P-388), Mouse mammart carcinoma (FM-3A), Human histiocytic lymphoma (U-937)
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