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Several final compounds showed potent in vitro cytotoxic activity on a small panel of cancer cell lines, but with no selectivity against nonmalignant fibroblasts BJ and MRC‐5.
Results suggest that the N-(4-(chlorodifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide scaffold is a useful template for designing selective BCR-ABL1-directed anticancer agents, with compound 9c as an encouraging lead for further optimisation and mechanistic studies.
Both in vitro and computational analyses demonstrated that compounds 11, 12, and 13 exhibit high affinity for the A Cα subunit of protein kinase A, suggesting a kinase‐targeted mechanism of action, providing a structural foundation for future design strategies to optimize the potency of these lead compounds.
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