644965-53-7Relevant academic research and scientific papers
Synthesis of C(2)-Substituted manno-Configured Tetrahydroimidazopyridines and Their Evaluation as Inhibitors of Snail β-Mannosidase
Terinek, Miroslav,Vasella, Andrea
, p. 3482 - 3509 (2007/10/03)
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 (Ki= 6 nM, non-competitive); the aniline 35 is the strongest competitive inhibitor (Ki=8 nM).
