Reactivity of 1-Aryl-Pyrazol-3-one, key intermediates for the access to new biocative small molecules

Pyrazolone derivatives are five membered important heterocyclic ring having one or two additional keto (CO) groups. Recently, pyrazol-3-ones containing tricycles have been investigated for their anticancer effects (1) especially as DNA and topoisomerase II modulators (2). Due to the easy preparation and to their interesting antiproliferative activity, in relation to our promising outcomes, we focused our studies on the synthesis and the biological evaluation of selected substituted-1-Aryl-Pyrazol-3-ones as new promising lead compounds. The nature and position of various substituents on the 1-aryl moiety have a crucial influence on the modulation of the tautomeric equilibrium, typical of this class of compounds. Thus, we explored adequate reaction conditions to allow a convenient regioselective control for the introduction of electrophilic substituents on a specific position, kept approachable by the tautomeric equilibrium. In particular, preliminary series of reactions with selected electrophiles have been carried out on derivatives a-c and further on e-g in order to clarify the substitution site. Herein we present our preliminary results on the regioselective reaction with selected strategic electrophiles along with the antiproliferative activity (NCI) of derivatives e-g.