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

Ergun B., Teresa Nunez M., Labeaga L., Ledo F., Darlington J., Bain G., ...More

Arzneimittel-Forschung/Drug Research, vol.60, no.8, pp.497-505, 2010 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 8
  • Publication Date: 2010
  • Doi Number: 10.1055/s-0031-1296318
  • Journal Name: Arzneimittel-Forschung/Drug Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.497-505
  • Keywords: Aryl propanoic acids, COX-1/2 inhibitors, Leukotriene B-4, Pyrazole, AMIDE DERIVATIVES, ANTIINFLAMMATORY COMPOUNDS, INFLAMMATION, AGENTS, COX-2, MEDIATORS, MECHANISM, CANCER
  • Gazi University Affiliated: Yes

Abstract

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. © ECV · Editio Cantor Verlag.