Anti-inflammatory activity of substituted 1,3,4-oxadiazoles.
Various 5-[[(acetamidophen-4-yl)oxy]methyl]-2-(p-substituted phenylamino)-1,3,4-oxadiazoles (4a-4d) were synthesized by cyclization of the corresponding N1-[[(acetamidophen-4-yl)oxy]acetyl]- N4-(p-substituted phenylamino)-3-thiosemicarbazides (3a-3d). All four of the thiosemicarbazides [250 mg/kg, orally (p.o.)] and the corresponding oxadiazoles (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 denaturation, and this activity ranged from 27 to 68%. No correlation was seen between the anti-inflammatory activity of 3a-4d and the inhibition of denaturation 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.
Nargund
L V
LV
Department of Pharmaceutical Chemistry, College of Pharmacy, J. N. Medical College, Belgaum, India.
Reddy
G R
GR
Hariprasad
V
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011489:Protein Denaturation / Q000187:drug effects; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010069:Oxadiazoles; D012710:Serum Albumin, Bovine; D002351:Carrageenan; D007213:Indomethacin