Synthesis and Biological Evaluation of Some N-Arylpyrazoles and Pyrazolo{[}3,4-d]pyridazines as Anti-Inflammatory Agents

A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-k was prepared from diacetyl pyrazoles 2a-e. The reaction of 2d and 2e with hydrazine hydrate gave pyrazolo{[}3,4-d]pyridazine derivatives 4a-b. Furthermore, the reaction of 2a-e with thiosemicarbazide afforded pyrazolo{[}3,4-d]pyridazine thiocyanate salts 5a-e. The synthesized compounds were subjected to in vivo anti-inflammatory and ulcerogenic activity measurements, in addition to determination of their in vitro COX selectivity, to give a full profile about their anti-inflammatory activities. Compounds 3c, 3f, 3i, and 3e showed significant anti-inflammatory activity among the synthesized compounds. Moreover, docking studies were performed to give an explanation for their anti-inflammatory activity through COX selectivity.