Exploiting the Versatile Reactivity of Aryldiazonium Tetrafluoroborate Salts in the Synthesis of New Isochromene-Fused CF3-Substituted Pyrazoles with Anticancer Potential

Abstract

Pyrazoles, and in particular their fluorinated derivatives, are valuable heterocyclic moieties in medicinal chemistry. Our research group recently developed a one-pot, two-step synthesis of pyrazolo[3,4-c]isochromenes, combining two privileged structures into a single hybrid molecule. Based on the preliminary anticancer screening results of these derivatives, herein, we designed a next-generation compound library focused on the derivatization of a specific portion of the 1-(trifluoromethyl)-3,5-dihydroisochromeno[3,4-c]pyrazole scaffold via late-stage functionalization. The diverse reactivity of aryldiazonium tetrafluoroborate salts was leveraged to achieve this and generate a small but varied compound library. The new series was tested for their anticancer properties and selected derivatives demonstrated pro-apoptotic activity in the human cervical carcinoma cell lines HeLa. The obtained results highlight these structures as valid candidates for further biological studies, while the streamlined synthetic route offers a facile approach to further structural analogs.