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

Abstract

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 LTB₄ formation inhibitory activity using an assay with activated human polymorphonuclear leukocyte (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC₅ = 1.5µM) and COX-2 (IC₅ = 1.6µM inhibitory activity, whereas compound 4 b and 4 f resulted in the inhibition of 5-LO-mediated LTB₄ formation at 14 and 12µM IC₅ values, respectively, without any significant inhibition on COX isoforms.

Key word

Aryl propanoic acid - COX-1/2 inhibitors - Leukotriene - Pyrazole

• Reference

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