Monocyclic, Substituted Imidazoles as Glycosidase Inhibitors

A range of 4‐monosubstituted and 2,4‐disubstituted 1 H ‐imidazoles and 1 H ‐imidazole‐1‐ethanols (RC(4): CH 2 CH 2 Ph, CHOHCH 2 Ph, Ph, or Me; RC(2): CH 2 OH, CHOHCH 2 OH, CN, or CH 2 NHAc) were prepared and tested as inhibitors of α ‐ and β ‐glucosidases and of a β ‐galactosidase. A new access to 4‐(2‐phenylethyl)‐1 H ‐imidazoles starting from 4‐phenylbutan‐1‐ol was elaborated. The strongest inhibitors are the 2‐substituted 4‐(2‐phenylethyl)‐1 H ‐imidazoles 24a and 26a (RC(2): CH 2 OH and CHOHCH 2 OH) and the 2‐phenylethanol 34 . They inhibit the β ‐galactosidase from bovine liver and the β ‐glucosidase from Caldocellum saccharolyticum with inhibition constants in the micromolar range, but do not inhibit the α ‐glucosidase from brewer's yeast.