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Arzneimittelforschung 2010; 60(8): 497-505
DOI: 10.1055/s-0031-1296318
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

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

Burcu çaliŞkan Ergün
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey
,
Maria Teresa Nuñe
2   Faes Farma, S.A., Departamanto de Investigacion, Bilbao, Spain
,
Luis Labeaga
2   Faes Farma, S.A., Departamanto de Investigacion, Bilbao, Spain
,
Francisco Ledo
2   Faes Farma, S.A., Departamanto de Investigacion, Bilbao, Spain
,
Janice Darlington
3   Amira Pharmaceuticals, San Diego, CA, USA
,
Gretchen Bain
3   Amira Pharmaceuticals, San Diego, CA, USA
,
Bilge çakir
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey
,
Erden Banoglu
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2011 (online)

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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
 

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