Expanding the chemical space: Discovery of new anticancer 3‐arylbenzofuran derivatives

Abstract A new chemical space was generated via C 2 ‐functionalization of 3‐arylbenzofurans. Mannich reaction of 3‐arylbenzofurans with secondary amines and formaldehyde allowed for installation of aminomethyl unit at C 2 position of benzofurans. A formyl group at C 2 site introduced as a result of Vilsmeier‐Haack formylation of 3‐arylbenzofurans was employed as a reacting partner for three‐component Kabachnik‐Fields reaction with various amines and triethyl phosphite to give a wide variety of aminomethylphosphonates. Furthermore, several benzo[ d ]oxazoles and pyrrolo[1,2‐ a ]quinoxalines were prepared by using the formyl group. Biological screening of the synthesized compounds revealed that the benzofuran bearing a pyrrolo[1,2‐ a ]quinoxaline moiety ( 5b ) most potently inhibited the viability of human blood cancer cells, but not solid tumor cells. Caspase activity assay, analysis of Annexin V‐positive cells, and Western blot analysis indicated that 5b ‐induced death of human lymphoma U937 cells could result from its potential to induce the caspase‐dependent apoptotic death of blood cancer cells with inhibition of ERK activation.