Facile synthesis of bis(4,5-dihydro-1H-pyrazole-1-carboxamides) and their thio-analogues of potential PGE2 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 50 mg/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 10 mg/kg of body weight). Ulcerogenic liability for the most promising prepared anti-inflammatory active agents (2b,c,e and f) (at a dose of 50 mg/kg of body weight) using indomethacin as a reference standard (at a dose of 10 mg/kg of body weight) indicated that compounds 2b and c exhibit lower ulcer index values than the used reference standard itself. PGE2 inhibitory properties of the highly promising synthesized anti-inflammatory active agents (2b,c,e and f) were determined by PGE2 assay kit technique, which reveal remarkable activities coincide greatly with the observed anti-inflammatory properties.

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