Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors☆

Design and synthesis of some thiazolotriazolyl esters as anti-inflammatory and analgesic agents

“…Besides, the literature survey revealed that derivatization (esterification or amidation) of carboxylic acid function of representative NSAIDs, resulted in an increased antiinflammatory activity with reduced ulcerogenic effect (Galanakis et al, 2004;Kalgutkar et al, 2000Kalgutkar et al, , 2002Kalgutkar et al, , 2005Khanna et al, 2006;Zhong et al, 2009). Based on these findings and as part of our continuous efforts in this area, it was thought to be interesting to combine thiazolo[3,2-b]-1,2,4-triazole condensed ring with an ester side chain to elucidate the essential structure requirements in relation to activity.…”

A novel phenol-bound pectic polysaccharide fromDecalepis hamiltoniiwith multi-step ulcer preventive activity

“…Indeed, NSAIDs are used daily by approximately 30 million people world wide, constituting a world market in excess of $2 billion. Associated serious side effects are ulceration and gastric bleeding, which are due to inhibiting cyclooxygenase-1 activity that is required for mucosal protection [4] . Gastric lesions develop due to loss of the delicate balance between gastro-protective and aggressive factors.…”

“…Reduction in gastroprotective factors, such as mucus, bicarbonate secretion and gastric mucosablood flow, and enhancement of aggressive factors, such as increase of acid/pepsin secretion and H pylori infection, results in gastric ulceration [1,2] . Mucosal damage, an initial step in ulcer development, has been known to be due to oxidative stress (OS) by Reactive Oxygen Species (ROS), hypersecretion of HCl through H + , K + -ATPase action [5] , harboring of H pylori on the damaged mucin layer [6] , and the blockade of the cyclooxygenase enzyme system by NSAIDS [4] , as depicted in Figure 1. A modest approach to control ulceration, therefore, is via stimulation of gastric mucin synthesis, enhancement of antioxidant levels in the stomach, scavenging of ROS, inhibition of H + , K + -ATPase and H pylori growth [7] .…”

Substituted aminoalcohol ester analogs of indomethacin with reduced toxic effects

“…There are reports on indomethacin esters and amides being cox-2 selective inhibitors (Kalgutkar et al, 2005;Khanna et al, 2006); hence, in addition, we expect that these esters, until they remain intact in the circulation, might afford gastric protection by having selectivity for cox-2 enzyme. These derivatives cannot be called prodrugs because unlike prodrugs they have a biological action (anticholinergic) before being hydrolyzed for release of the parent moiety.…”