Synthesis of New C(2)-Substituted gluco-Configured Tetrahydroimidazopyridines and Their Evaluation as Glucosidase Inhibitors

✍ Scribed by Bhagavathy Shanmugasundaram; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: German
• Weight: 146 KB
• Volume: 88
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200590199

✦ Synopsis

Abstract

The gluco‐configured C(2)‐substituted tetrahydroimidazopyridines 8–14 were prepared and tested as inhibitors of the β‐glucosidases from Caldocellum saccharolyticum and from sweet almonds, and of the α‐glucosidase from brewer's yeast. All new imidazopyridines are nanomolar inhibitors of the β‐glucosidases and micromolar inhibitors of the α‐glucosidase. The 3‐phenylpropyl derivative 14 proved the strongest inhibitor of the Caldocellum β‐glucosidase (K~i~ = 0.9 nM), only slightly weaker than the known 2‐phenylethyl analogue 7, and the propyl derivative 13 is the strongest inhibitor of the sweet almond β‐glucosidases (K~i~ = 3.2 nM), again slightly weaker than 7. There is no strong dependence of the inhibition on the nature of the C(2)‐substituent and no clear correlation between the inhibitory strength of the known manno‐configured imidazopyridines 2–6 and the gluco‐analogues 8–12. While most manno‐imidazopyridines are competitive inhibitors, the gluco‐analogues proved non‐competitive inhibitors of the Caldocellum β‐glucosidase and mixed‐type or partial mixed‐type inhibitors of the sweet almond β‐glucosidases.