Synthesis and CYP24 inhibitory activity of 2-substituted-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives

The synthesis of novel 2-benzyl- and 2-benzylidene-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives and their inhibitory activity versus kidney mitochondrial 25-hydroxyvitamin D3 24-hydroxylase (CYP24) is described. The 2-benzylidenetetralone derivatives were found to be very weak inhibitors (IC50 20 >100 μM), whereas the 2-benzyltetralone derivatives showed promising inhibitory activity (IC50 0.9 μM for the most active derivative) compared with ketoconazole (IC50 20 μM).