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g. but-2-ynyloxy and pent-2-ynyloxy at different positions including the most active compound 13h with IC50 value in the low picomolar range (0.09 nM). Aromatase inhibition results paired with molecular dynamics studies provided a clear structure activity relationship and favourable dual binding mode was verified. Toxicity assays and CYP selectivity profile studies for some example compounds were performed to assess the safety profile of the prepared inhibitors providing the basis for the 4th generation nonsteroidal aromatase inhibitors