Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: Potent and selective aromatase inhibitors

The synthesis and the aromatase (CYP19) inhibitory activity of 5-[(aryl)(imidazol-1-yl)methyl]-1H-indoles were reported. Among the tested racemate compounds, 5-[(4-chlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 8b emerged as a potent CYP19 inhibitor (IC50 = 15.3 nM). Chiral chromatography allowed isolation of the (+) enantiomer 8b2, which was about twice as active as the racemate (IC50 = 9 nM).

Graphical abstractThe synthesis and the aromatase (CYP19) inhibitory activity of 5-[(aryl)(imidazol-1-yl)methyl]-1H-indoles were reported. Among racemate compounds tested, 5-[(4-chlorophenyl)(1H-imidazol-1-yl)methyl-1H-indole 7b emerged as potent CYP19 inhibitor (IC50 = 15.3 nM). And one of its enantiomers 7b2 was found to be more active (IC50 = 9 nM).Figure optionsDownload full-size imageDownload as PowerPoint slide