Amide Derivatives of [5-Chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic Acids as Potential Analgesic and Anti-Inflammatory Compounds

✍ Scribed by Erden Banoglu; Berna Okçelik; Esra Kupeli; Serdar Ünlü; Erdem Yeşilada; Merc? Amat; Joan F. Caturla; M. Fethi Sahin

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 93 KB
• Volume: 336
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200300723

✦ Synopsis

In this study, we have explored the prevention of gastric side effects such as gastric lesions and bleeding while maintaining the high analgesic and anti-inflammatory activities by the derivatization of the carboxylate moiety into amides in [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids. We have tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. Compounds 3a, 3d, 3e, 3j and 3k potent analgesic and anti-inflammatory activities without gastric lesions in the tested animals. Therefore, conversion of the carboxylate moiety into certain amide derivatives generated potent analgesic and anti-inflammatory compounds while eliminating the gastrointestinal side effects. Cyclooxygenase (COX)-selectivity of the active compounds was also investigated by using in vitro human whole blood assay. Compounds 3a, 3e, 3h and 3k selective inhibition of COX-2 to some extent although the inhibitory activity was not very potent.