Synthesis, characterization and molecular docking study of new 4-acetamidoalkyl pyrazoles as B-raf /COX-2 inhibitors

The success of COX-2 inhibitors containing a pyrazole moiety has highlighted the importance of these heterocyclics in medicinal chemistry [1]. Meanwhile, recent researches have shown the potency and selectivity of pyrazoline derivatives against B-RafV600E after being identified through high-throughput screening [2]. Both pyrazole and pyrazoline are reported to be backbone moieties of anti-cancer molecules [3]. These compounds are also reported to possess significant antipyretic, antidepressant, antiviral, antifungal, antitumor, and anti-inflammatory activities [4-6].Some new 4-acetamidoalkyl pyrazoles were synthesized by efficient, one-pot three-component reaction of 3,5-dimethyl-1-phenyl-1H-pyrazole or 3-methyl-1-phenyl-1H-pyrazol-5-ol, aromatic aldehydes and acetonitrile in the presence of chlorosulfonic acid at room temperature. The products were characterized on the basis of IR, 1H NMR, and 13C NMR data and evaluated as potential COX-2 and B-Raf inhibitors by molecular docking studies.