When we see the presently available NSAIDs, most of them have ulcerogenicity as one of the common side effect. Ulcerogenicity can be explained by the metabolism of Arachidonic acid into various metabolites. Most of the drugs (NSAIDs) act by inhibiting the prostaglandins. But some of the prostaglandins are essential as cytoprotective layer and hence selective inhibitors of Cyclooxygenase –II (COX-II) and 5-LO (Lipoxygenase) are better tolerable and hence we can call these drugs as non ulcerogenic NSAIDs. Though these 2 enzymes (COX-II and 5-LO) were the targets of many drug discovers (as for as my knowledge goes, 1996-98 there were many papers regarding the selective inhibitors).
Now Oliver Werz and co workers have come with some new compounds 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (with some structural variations like α substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue) a derivative of pirinixic acid [PA, 2-(4-chloro-6-(2,3-dimethylphenylamino) pyrimidin-2-ylthio)acetic acid.
Significance of this research is the, less pronounced inhibition of cyclooxygenases-1/2. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacologial profile and a potential for therapeutic use. More……
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