Polysubstituted pyrazoles, part 6. Synthesis of some 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazol-3-carbonyl derivatives linked to nitrogenous heterocyclic ring systems as potential antitumor agents.

The synthesis of two novel series of 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazoles linked to either polysubstituted 1H-pyrazole counterparts through a carbonyl bridge, or to some biologically-active nitrogenous heterocycles by an amide linker, is described. Ten of the newly synthesized compounds were selected by the National Cancer Institute (NCI) in vitro disease-oriented antitumor screening to be evaluated for their antitumor activity. The most active six compounds 2, 3, 6, 7, 13 and 14 revealed a significant broad spectrum of antitumor potential against most of the tested subpanel tumor cell lines at the GI(50) and TGI levels, together with a mild cytotoxic (LC(50)) activity. The pyrazolinedione analog 7 displayed remarkable growth inhibition and cytostatic effects (GI(50) and TGI MG-MID values 0.67 and 53.8microM, respectively). Compounds 13 (GI(50), TGI, and LC(50) MG-MID values 0.08, 30.9 and 93.3microM) and 14 (GI(50), TGI, and LC(50) MG-MID values 0.36, 8.78 and 69.3microM, respectively) proved to be the most active antitumor members identified in this study. Copyright 2010 Elsevier Ltd. All rights reserved.