Synthesis of C(2)-Substituted manno-Configured Tetrahydroimidazopyridines and Their Evaluation as Inhibitors of Snail β-Mannosidase

✍ Scribed by Miroslav Terinek; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: German
• Weight: 392 KB
• Volume: 86
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200390293

✦ Synopsis

Abstract

It was shown that retaining β‐glucosidases and galactosidases of families 1–3 feature a strong interaction between C(2)OH of the substrate and the catalytic nucleophile. An analogous interaction can hardly take place for retaining β‐mannosidases. A structureactivity comparison between the inhibition of the β‐glucosidase from Caldocellum saccharolyticum (family 1) and β‐glucosidase from sweet almonds by the gluco‐imidazoles 1–6, and the inhibition of snail β‐mannosidase by the corresponding manno‐imidazoles 8–13 does not show any significant difference, suggesting that also the mechanisms of action of these glycosidases do not differ significantly. For this comparison, we synthesized and tested the manno‐imidazoles 9–13, 28, 29, 32, 35, 40, 41, 43, 46, 47, and 50. Among these, the alkene 29 is the strongest known inhibitor of snail β‐mannosidase (K~i~=6 nM, non‐competitive); the aniline 35 is the strongest competitive inhibitor (K~i~=8 nM).