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KMID : 0043320070300060678
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Archives of Pharmacal Research
2007 Volume.30 No. 6 p.678 ~ p.684
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Benzimidazole Condensed Ring Systems: New Synthesis and Antineoplastic Activity of Substituted 3,4-Dihydro- and 1,2,3,4-Tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine Derivatives
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Abdel-hafez Atef Abdel-monem
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Abstract
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As part of an ongoing effort to develop new antineoplastic agents, a series of substituted 3,4- dihydro- and 1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine derivatives (5-19) were synthesized. 1,2,3,4-Tetrahydrobenzo[4,5]imidazo[1,2-a]pyrimidine-2-one derivatives (5-7) were prepared via one-pot two-component thermal cyclization reaction of 2-aminobenzimidazole 1 and P-substituted methyl cinnamates (2-4). Vilsmir-Haack formylation of these derivatives (5-7) afforded the 2-chloro-3-carboxaldehyde targets (8-10) followed by nucleophilic displacement of the chloro atom in the 3-carboxaldehyde compounds (8-10) to yield the remaining final targets (11-19). The structures of the synthesized derivatives (5-19) were confirmed by means of IR, 1H NMR, MS and elemental analyses. The synthesized derivatives (5-19) were subjected to the National Cancer Institute (NCI) in vitro disease human cell screening panel assay. 2- Chloro-4-phenyl-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (8, NCI 722731) and 4-(4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)-3,4-dihydrobenzo[4,5]imidazo [1,2-a]pyrimidine-3-carboxaldehyde (18, NCI 722739) showed a variable degree of antineoplastic activity against some of the cell lines tested. 2-Chloro-4-(4-nitrophenyl)-3,4-dihydrobenzo[ 4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (10, NCI 722743) exhibited good in vitro antineoplastic activity with subpanel disease selectivity against all the cell lines tested with log10 GI50 (M), the concentration that inhibits 50% of cell growth, values ranging from ?.08 to < -8.00.
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KEYWORD
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Benzimidazole, Methyl cinnamates, Pyrimido[1, 2-a]benzimidazole, Azinazoles, Anticancer, Cytotoxicity
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