Convenient synthesis, anti-inflammatory, analgesic and ulcerogenic activites of some new bis-hydrazones and pyrazole derivatives

The reaction of acid hydrazides (1a-c) with 2-chloro-1-(4-chlorophenyl)ethanone (2a) or 2-bromo-1-(4-bromophenyl)ethanone (2b) afforded bis-hydrazones 6a-d, while the reaction of la-c with 2-oxo-N-arylpropanehydrazonoyl chlorides (3a,b) furnished N-(aryl)propanehydrazonoyl chlorides 8a-c. The reaction of the latter chlorides with sodium benzenesulfinate furnished sulfones 11a-c. On the other hand, treatment of benzothiazole-2-carbohydrazide (1c) with the appropriate ketones yielded the corresponding hydrazones 13a,b, while the reaction of 1c with 2-(ethoxymethylene)malononitrile (14) or with 2-[bis(methylthio)methylene]malononitrile (16) afforded pyrazole derivatives 15 and 17, respectively. In acute toxicity study, no mortalities were observed for the tested compounds. All the tested compounds showed significant anti-inflammatory activity, while some of them exhibited potent analgesic activity. In addition, all compounds exhibited lower ulcerogenic effects than the standard ketoprofen.