%0 Journal Article
%T Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors
%A Mange Ram Yadav
%A Shrikant T. Shirude
%A Devendra S. Puntambekar
%A Pinkal J. Patel
%A Hetal B. Prajapati
%A Arvind Parmar
%A R. Balaraman
%A Rajani Giridhar
%J Acta Pharmaceutica
%@ 1846-9558
%D 2007
%I 
%R 10.2478/v10007-007-0002-z
%X 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 ¦̀mol L-1 and COX-1 enzyme inhibition of 44% at 88 ¦̀mol 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 ¦̀mol L-1) and higher COX-1 enzyme inhibition (53% at 88 ¦̀mol 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.
%K 1
%K 2
%K 5-oxadiazole
%K 1
%K 2
%K 5-oxadiazole N-oxide
%K COX-2 inhibitor
%U http://versita.metapress.com/content/w72wx90w4216p3v4/?p=d5e6c6f66cab4a78807e2215f9f534b2&pi=1