AbstractA novel series of inhibitors of the HPV11 E1E2 proteinprotein interaction was identified. These inhibitors, which were discovered as a result of high‐throughput screening, feature an indandione system spiro‐fused onto an appropriately substituted tetrahydrofuran ring. Early stability studies indicated, surprisingly, that this particular series of compounds were readily converted, in binding assay buffer, to the corresponding carboxylates. NMR and mass spectrometry techniques were used to elucidate the structures of these products and the mechanism by which they are produced.