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 D(3) 24-hydroxylase (CYP24) is described. The 2-benzylidenetetralone derivatives were found to be very weak inhibitors (IC(50) 20 >100 microM), whereas the 2-benzyltetralone derivatives showed promising inhibitory activity (IC(50) 0.9 microM for the most active derivative) compared with ketoconazole (IC(50) 20 microM).
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, Wales, UK.
Sook Wah
SW
Yee
Claire
C
Simons
D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D044024:Tetralones / Q000138:chemical synthesis* / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase
D065607:Cytochrome P-450 Enzyme Inhibitors; D044024:Tetralones; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase