Anti-inflammatory Activity of Substituted 1,3,4-Oxadiazoles

□ Various 5-[[(acetamldophen-4-yl)oxy] methyl]-2-(p-sub- stituted phenylamino)-1,3,4-oxadiazoles (4a-4d) were synthesized by cyclization of the corresponding A/1- [[(acetamidophen-4-yl)oxy] acetyl] - A/Mp-substituted phenylamlno)-3-thiosemicarbazides (3a-3d). All four of the thiosemicarbazides [250 mg/kg, orally (p.o.)] and the corresponding oxadiazoies (250 mg, p.o.) possessed anti-inflammatory activity. In the Carrageenan-induced edema test in rat paw, the activity ranged from 28 to 47% for 3a-3d and 44 to 63% for 4a-4d, with indomethacin (10 mg/kg, p.o.), used as the standard reference drug, showing 88.5 % protection. The compounds (1 mM) were also tested for the Inhibition of bovine serum albumin dénaturation, and this activity ranged from 27 to 68 %. No correlation was seen between the antiinflammatory activity of 3a-4d and the inhibition of dénaturation of bovine serum albumin. The low toxicity of these compounds was reflected by their high approximate 50% lethal dose (LD50) values, ranging from 2000 to 2500 mg/kg.