Organocatalytic synthesis and sterol 14α-demethylase binding interactions of enantioriched 3-(1H-1,2,4-triazol-1-yl)butyl benzoates

1H-1,2,4-Triazole reacted with 2-butenal in the presence of diaryl prolinol silyl ether 3 and benzonic acid to give 3-(1H-1,2,4-triazol-1-yl) butanal 4, which was subsequently reduced and then treated with various acyl chloride to generate enantioriched 3-(1H-1,2,4-triazol-1-yl) butyl benzoates 6. Some of triazoles 6 exhibited strong binding interactions with the cytochrome P450-dependent sterol 14 alpha-demethylase (CYP51). For example, compound (R)-6f showed the best binding activity with K-d 0.3381 mu M. (C) 2009 Elsevier Ltd. All rights reserved.