Synthesis of 3-(2-pyridylethyl)benzoxazolinone derivatives: Potent analgesic and antiinflammatory compounds inhibiting prostaglandin E2

Article abstract of DOI:10.1021/jm00085a018

Fourteen new 3-[2-(2- and/or 4-pyridyl)ethyl]benzoxazolinone derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones. Their chemical structures have been proven by IR, ¹H-NMR, and elemental analysis. Analgesic activities of these compounds were investigated by a 'Modified Koster's Test'. Except for compounds 10 and 11, all the new derivatives showed higher analgesic activities than aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. The compounds (6, 7, 8, 9, 14, and 17) that showed high antiinflammatory activity were then further screened for their ability to inhibit prostaglandin E₂ (PGE₂) induced paw edema. Although all the benzoxazolinone derivatives synthesized in this study showed higher antiinflammatory activity compared to indomethacin, those without a substituent at the 6-position of the ring were significantly more active than the rest of the group, and their ulcerogenic activities and ED₅₀ values indicate them as promising derivatives for further study.