A. Abdel-Hafez
Jun 1, 2007
Citations
0
Influential Citations
67
Citations
Quality indicators
Journal
Archives of Pharmacal Research
Abstract
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-dihy-drobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (10, NCI 722743) exhibited goodin 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 -5.08 to <-8.00.