Design and synthesis of functionalized chloro-substituted quinolines with potential antitumoral activity

Quinoline core is one of the most investigated azanaphthalene scaffold as a privileged structure. The quinolinic framework is related to many biological activities such as antimalarial, antifungical, antitubecular and anticancer.1 Recently, our research group has reported the regioselective functionalization of chloro-substituted quinolines that are common intermediates in medicinal chemistry.2 In this work, we have designed and synthesized C4-substituted cloroquinolines in order to obtain a library of bioactive compounds as potential inhibitors of the epidermal growth factor receptor (EGFR). After a methodological study using turbo Grignard, the organomagnesium intermediate could be reacted with different electrophiles to generate the desired chloroquinoline derivatives in good yields. The antiproliferative activity of these quinolines against diverse cancer cell lines such as glioblastoma is under investigation.