Amide derivatives of [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids as potential analgesic and anti-inflammatory compounds.

Abstract

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.

• Authors: Erden Banoglu, Berna Okçelik, Esra Kupeli, Serdar Unlü, Erdem Yeşilada, Mercé Amat, Joan F Caturla, M Fethi Sahin
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 336 Issue 4-5 Pg. 251-7 (Jul 2003) ISSN: 0365-6233 [Print] Germany
• PMID: 12916060 (Publication Type: Journal Article)

Chemical References

• (5-chloro-6-(2-chlorobenzoyl)-2-benzoxazolinone-3-yl)acetic acid
• (5-chloro-6-(2-fluorobenzoyl)-2-benzoxazolinone-3-yl)acetic acid
• Acetates
• Analgesics
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Membrane Proteins
• Oxazoles
• Cyclooxygenase 1
• Cyclooxygenase 2
• PTGS1 protein, human
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Ptgs1 protein, mouse

Topics

• Acetates (chemical synthesis, chemistry, pharmacology)
• Analgesics (chemical synthesis, chemistry, pharmacology, toxicity)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, chemistry, pharmacology, toxicity)
• Cyclooxygenase 1
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (chemical synthesis, chemistry, pharmacology, toxicity)
• Disease Models, Animal
• Edema (chemically induced, drug therapy)
• Humans
• In Vitro Techniques
• Isoenzymes (antagonists & inhibitors, blood)
• Lethal Dose 50
• Male
• Membrane Proteins
• Mice
• Oxazoles (chemical synthesis, chemistry, pharmacology)
• Pain Measurement
• Prostaglandin-Endoperoxide Synthases (blood)
• Stomach Ulcer (chemically induced)
• Structure-Activity Relationship