Design, synthesis, and biological evaluation of N-[1-(6′-chloropyridazin-3′-yl)-3-(4"-substitutedphenyl)-1H-pyrazole-5-yl]alkanamides as anti-inflammatory agents

A series of structurally diverse N-[1-(6 '-chloropyridazin-3 '-yl)-3-(4 ''-substitutedphenyl)-1H-pyrazole-5-yl]alkanamides 5(a-r) has been designed and synthesized via Aliquat 336 catalyzed amidation of 5-amino-3-aryl-1-(6 '-chloropyridazin-3 '-yl)pyrazoles 3(a-c). The target compounds were designed on basis of the results obtained from the study of Lipinski's rule of five and binding interactions with target protein 3LN1. Eventually, compounds 5(a-r) were screened for their in vitro anti-inflammatory action by using inhibition of albumin denaturation and membrane stabilization assay. It has been found that all the synthesized compounds obeyed Lipinski's rule of five (n(violations) = 0-1) and showed weak to strong binding interactions with dock score range -8.0 to -9.9 kcal/mol. All alkanamides exhibited moderate to excellent activity as compared to the standard drug, Aspirin. Interestingly, the results indicated that the compound 5a may act as a promising medicinal lead as an anti-inflammatory agent for in vivo and clinical testing in future.