Discovery of New Imidazo[2,1-<i>b</i>]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising <i>In Vitro</i> and <i>In Vivo</i> Anti-melanoma Activity

BRAF is an important component of MAPK cascade. Mutation BRAF, in particular V600E, leads to hyperactivation the pathway and uncontrolled cellular growth. Resistance selective inhibitors mutated a major obstacle against treatment many cancer types. In this work, series new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect was investigated, structure–activity relationship discussed. Antiproliferative activity target compounds tested NCI-60 cell line panel. The most active further obtain their IC50 values cells. Compound 27c with open chain 38a cyclic sulfamide showed highest enzymatic assay, both able inhibit phosphorylation MEK ERK. selected for testing its vivo melanoma. Cellular animal activities are reported.