Syntheses, characterization and evaluation of novel 2,6-diarylpiperidin-4-ones as potential analgesic-antipyretic agents

•One pot synthesis of the title compounds.•Comparable or even better analgesic activity than that of diclofenac sodium.•Antipyretic activity of title compounds similar to that of paracetamol.•Excellent correlation of in vitro hydrolysis profiles with the observed activities.•Excellent correlation of partition coefficient values with the observed activities.

A novel series of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-one derivatives (1c–3c and 5c) were synthesized, via base catalyzed nucleophilic substitution of N-chloroacetyl-2,6-diarylpiperidin-4-ones (1b–6b) with N-methyl piperazine. The newly synthesized compounds were characterized by FTIR, Mass and NMR spectral studies. All the compounds were screened for their possible analgesic and antipyretic activities. The compound 2c exhibited promising antipyretic activity, comparable to that of paracetamol at 60 mg/kg dose. The compounds 2b and 2c showed significant analgesic profile at a dose of 60 mg/kg and were also found to be more potent than the reference drug, diclofenac sodium. Thus, it can be concluded that the synthesized 2,6-diarylpiperidin-4-ones exhibit promising antipyretic and analgesic activities and could be potential drug candidates.

Graphical abstractVarious 2,6-diarylpiperidin-4-ones were prepared in a one pot multi-component Mannich reaction by condensing suitably substituted aromatic aldehydes, ketone and ammonium acetate in equimolar ratio, using ethanol as solvent.Figure optionsDownload full-size imageDownload as PowerPoint slide