Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB₄ formation

A set of 25 derivatives of 3-[1-(6-substituted-pyridazin-3-yl)-5-(4- substitutedphenyl)-1H-pyrazol-3-yl]propanoic acids has been synthesized and evaluated for their in vitro cyclooxygenase-1/2 (COX-1/ 2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes as well as for their 5-lipoxygenase (5-LO)-mediated LTB₄ formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC₅₀ = 1.5 μM) and COX-2 (IC₅₀ = 1.6 μM) inhibitory activity, whereas compounds 4b and 4 f resulted in the inhibition of 5-LO-mediated LTB₄ formation at 14 μM and 12 μM IC₅₀ values, respectively, without any significant inhibition on COX isoforms.