Synthesis, characterization and anti-inflammatory activity of novel pyrazolyl ketoamides

Compounds containing pyrazolylurea group are known to possess potent anti-inflammatory activity by inhibiting cell signalling system. One of the potent compounds has demonstrated CNS related adverse effects in human studies which has further intensified the quest to search potent but safe antiinflammatory agents. In the present study, an attempt has been made to modify the urea group into alpha-ketoamide group. The synthesis involved the coupling of 5-aminopyrazole with substituted alpha-keto acids in presence of a coupling agent to afford the desired compounds and the structures of the synthesized compounds have been confirmed by spectral data. Compounds have been screened for antiinflammatory activity by carrageenan induced rat paw method. Compounds 6c,.6e and 6f demonstrate greater than 70% paw oedema protection when compared with indomethacin. The preliminary structure activity relationship suggests that the electron withdrawing groups are essential for potent antiinflammatory activity of compounds.