3-Oxabicyclo[3.3.1]nonenes: synthesis and investigation as tyrosyl-DNA phosphodiesterase 1 inhibitors

Compounds with a 3-oxabicyclo[3.3.1]nonane core were prepared from limonene and aromatic aldehydes containing methoxy groups and phthalaldehydes in the presence of montmorillonite K10 and were converted to aromatic amines containing this heterocycle. Some of the products were found to exhibit inhibitory activity in the reaction catalyzed by human tyrosyl-DNA phosphodiesterase 1 in the micromolar range. Bromo derivatives of amines, compounds 6b and 7b, which combine high inhibitory activity and low cytotoxicity, are promising for further studies in order to create new agents for the use in combined anticancer therapy.