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-substi-tuted-pyridazin-3-yl)-5-(4-substituted-phenyl)-1H-pyrazol-3-yl]propanoic acid 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 a well as for their 5-lipoxygenase (5-LO)-mediated LTB 4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocyte (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC 5 = 1.5µM) and COX-2 (IC 5 = 1.6µM inhibitory activity, whereas compound 4 b and 4 f resulted in the inhibition of 5-LO-mediated LTB 4 formation at 14 and 12µM IC 5 values, respectively, without any significant inhibition on COX isoforms.