<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml">A series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazole <italic>N</italic>-oxides were prepared and evaluated for COX-2 and COX-1 binding affinity <italic>in vitro</italic> and for anti-inflammatory activity by the rat paw edema method. <italic>p</italic>-Methoxy (<italic>p</italic>-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazole <italic>N</italic>-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1 and COX-1 enzyme inhibition of 44% at 88 μmol L-1 concentrations, but showed very low <italic>in vivo</italic> anti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, marked <italic>in vivo</italic> anti-inflammatory activity (71% at 25 mg kg-1) <italic>vs.</italic> celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest that <italic>p</italic>-methoxy (<italic>p</italic>-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/<italic>N</italic>-oxides.</abstract>

A series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazole N-oxides were prepared and evaluated for COX-2 and COX-1 binding affinity in vitro and for anti-inflammatory activity by the rat paw edema method. p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazole N-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1 and COX-1 enzyme inhibition of 44% at 88 μmol L-1 concentrations, but showed very low in vivo anti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, marked in vivo anti-inflammatory activity (71% at 25 mg kg-1) vs. celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest that p-methoxy (p-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/N-oxides.

Studies in 3,4-diaryl-1,2,5-oxadiazoles and their <italic>N</italic>-oxides: Search for better COX-2 inhibitors

Pharmacy Department Faculty of Technology and Engineering Kalabhavan, The M. S. University of Baroda, Vadodara-390 001, India

Acta Pharmaceutica

Studies in 3,4-diaryl-1,2,5-oxadiazoles and their -oxides: Search for better COX-2 inhibitors

A series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazole N-oxides were prepared and evaluated for COX-2 and COX-1 binding affinity in vitro and...

Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

Publié en ligne: 08 mars 2007

Pages: 13 - 30

DOI: https://doi.org/10.2478/v10007-007-0002-z

Mots clés
1,2,5-oxadiazole, 1,2,5-oxadiazole -oxide, COX-2 inhibitor

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