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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]pyrimi dine Derivatives
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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]pyrimi dine Derivatives
  • 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]pyrimi dine Derivatives
저자명
Abdel-hafez. Atef Abdel-monem
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2007년|30권 6호|pp.678-684 (7 pages)
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대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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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, $^1$H 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, NCl722731) 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-dihy-drobenzo[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 log$_{10}$ GI$_{50}$ (M), the concentration that inhibits 50% of cell growth, values ranging from -5.08 to <-8.00.