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Here, we describe the synthesis and evaluation of a class of cell‐permeable indeno‐oxadiazolopyrazine analogs as the anticancer agents. A new and facile approach to the synthesis of substituted analogs of indeno‐oxadiazolopyrazine is illustrated. We find that the designed indeno‐oxadiazolopyrazines, 3, 4, 10, 11, 15, and 16, act as potent anticancer agents compared to camptothecin, topoisomerase I...