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Domain-related knowledge promoted high-throughput cage scaffold screening from the ZINC15 database containing over 130 000 scaffolds and cooperated with combinatorial design to alleviate the lack of cage energetic materials. A dozen candidates were discovered that show excellent energy and safety performance, confirming the effectiveness of our strategy.Gold(I)-catalyzed [4 + 2] cycloaddition of indolylynamides and cyanamides (aminonitriles) is an efficient redox-neutral and atom-economic route to diversely substituted 1,3-diamino-β-car