Probing bioactive motifs through C(sp3)-H activation for the development of protease inhibitors

Nowadays, the C(sp2/sp3)-H activation reactions have been developed and established due to their great potentialities.1-2 Through them it is possible to carry out functionalization otherwise impracticable, enabling the activation of non-acidic unreactive CH bonds. Over the last years, the application of such reactions to complex molecules with biomedical relevance have appeared in the literature,3-4 although the activation of the less acidic and more unreactive C(sp3)-H bond remains a challenge. We set out to apply the 8-AQ directed C(sp3)-H activation reaction on complex molecules of biomedical interest, to insert additional chemical motifs that could be able to increase the inhibitory activity of the compounds toward a first selected target: β-secretase 1, a transmembrane protease involved in the formation of the amyloid plaques in the Alzheimer’s disease.