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Synthesis and evaluation of novel 7H-pyrrolo-[2,3-d]pyrimidine derivatives as potential anticancer agents.

Aim: Bladder cancer is a highly recurrent urologic malignancy with limited treatment approaches. Previously, we reported compound 11 is a FGFR3 inhibitor with significant antibladder cancer activity. Materials & methods: In this study, a series of 7H-pyrrolo-[2,3-d]pyrimidine derivatives were synthesized through ring formation and modification of compound 11 for anticancer activity evaluation. Results: Compound 13i is the most effective agent against human RT-112 bladder cancer cells. Notably, 13i strongly inhibits CK1δ without affecting FGFR3 activity. We generated 13i HCl to increase solubility and showed profound cell cycle accumulation at the sub-G1 phase and apoptosis in CK1δ-overexpressed bladder and ovarian cancer cells. Conclusion: These results indicate that compound 13i could be a lead compound for further development of novel anticancer agents.