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Cyclo-oxygenase enzymes are responsible for synthesis of prostaglandins, COX-1 is constitutive and synthesize the prostaglandins that responsible for gastric mucosa protection. While COX-2, is induced during inflammation processes. So; inhibition of COX-2 enzymes, while maintaining the activity of COX-1 enzymes, is the aim of synthesis of newer anti-inflammatory agents. Sulfonamides derivatives, and some heterocyclic rings as 2-amino thiazole,and 2-amino pyridine, will increase the selectivity of compounds toward COX-2 inhibition, rather than COX-1; due to their ability to incorporated in the side pocket that is present in the COX-2 hydrophobic channel, there fore, they are linked with many non selective Anti-inflammatory drugs to modify their selectivity, by that reduce the gastric ulceration associated with inhibition of COX-1 enzyme.