Facile synthesis of bis(4,5-dihydro-1H-pyrazole-1-carboxamides) and their thio-analogues of potential PGE(2) inhibitory properties.
A variety of bis(3-aryl-4,5-dihydro-1H-pyrazole-1-thiocarboxamides) 2a-h were prepared via reaction of bis(2-propen-1-ones) 1a-h with thiosemicarbazide in ethanolic KOH solution. Meanwhile, bis(3-aryl-4,5-dihydro-1H-pyrazole-1-carboxamides) 3a-d were obtained through reaction of 1a-d with semicarbazide hydrochloride in refluxing with acetic acid. Anti-inflammatory activity screening of the synthesized compounds 2a-f,h; 3a-d (at a dose of 50mg/kg of body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that many of the tested compounds reveal considerable anti-inflammatory properties, especially 2e and f which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10mg/kg of body weight). Ulcerogenic liability for the most promising prepared anti-inflammatory active agents (2b,c,e and f) (at a dose of 50mg/kg of body weight) using indomethacin as a reference standard (at a dose of 10mg/kg of body weight) indicated that compounds 2b and c exhibit lower ulcer index values than the used reference standard itself. PGE(2) inhibitory properties of the highly promising synthesized anti-inflammatory active agents (2b,c,e and f) were determined by PGE(2) assay kit technique, which reveal remarkable activities coincide greatly with the observed anti-inflammatory properties.
Barsoum
Flora F
FF
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Girgis
Adel S
AS
D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012663:Semicarbazides; D013329:Structure-Activity Relationship
D000577:Amides; D000893:Anti-Inflammatory Agents; D011720:Pyrazoles; D012663:Semicarbazides; C005151:thiosemicarbazide; D015232:Dinoprostone