Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4-Oxadiazole-2-thiones

Article abstract of DOI:10.3797/scipharm.aut-03-28

A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate), antiinflammatory (carrageenin induced rat's paw edema) and ulcerogenic effects as well as plasma prostaglandin E₂ (PGE ₂) level. The highest analgesic activity was achieved with compound 5a (0.5, 0.6, 0.7 mmol/kg b.wt.) in respect with mefenamic acid (0.4 mmol/kg b.wt.). Compounds 6h, 61 and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat's paw edema at dose level of 0.1mmol/kg, b.wt, compared with 58% inhibition of mefenamic acid (0.2mmol/kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE₂ level was displayed also with 6h, 61 and 5g (71, 70, 68.5% respectively, 0.1mmol/kg b.wt.) compared with indomethacin (60%, 0.01 mmol/kg b.wt.) as a reference drug. In addition 6i, 6k, 6p, 6r, 6t and 6v were devoid of any ulcerogenicity.