244138-64-5Relevant academic research and scientific papers
Tight-binding inhibition of jack bean α-mannosidase by glycoimidazole clusters
Pichon, Ma?va M.,Stauffert, Fabien,Bodlenner, Anne,Compain, Philippe
, p. 5801 - 5817 (2019/06/19)
The best multivalent effects observed in glycosidase inhibition have been achieved so far with jack bean α-mannosidase (JBα-man) using iminosugar clusters based on weakly binding mismatching active-site-directed inhibiting epitopes (inhitopes) in the d-gl
Structure-activity relationships in a series of C2-substituted gluco-configured tetrahydroimidazopyridines as β-glucosidase inhibitors
Li, Tiehai,Guo, Lina,Zhang, Yan,Wang, Jiajia,Zhang, Zhenxing,Li, Jing,Zhang, Wenpeng,Lin, Jianping,Zhao, Wei,Wang, Peng George
, p. 2136 - 2144 (2011/05/06)
Inhibition of glycoside hydrolases has widespread application in treatment of diabetes, viral infections, lysosomal storage diseases and cancers. Gluco-configured tetrahydroimidazopyridines are the most potent β-glucosidase inhibitors reported to date. Using transition state mimic strategy, a series of C2-substituted gluco-configured tetrahydroimidazopyridines were designed and synthesized. Compounds 3 (Ki = 0.64 nM) and 5 (Ki = 0.58 nM) showed stronger inhibitory potency against β-glucosidase. Maestro 9.1 was used to study the structure-activity relationships by docking the compounds into the β-glucosidase active sites. Crown Copyright
Very strong inhibition of glucosidases by C(2)-substituted tetrahydroimidazopyridines
Panday, Narendra,Canac, Yves,Vasella, Andrea
, p. 58 - 79 (2007/10/03)
The C(2)-substituted imidazoles 11, 15-17, 19, 21, 23/24, 28-31, 37, and 38 have been prepared from the known 2,3-unsubstituted imidazole 7 via the iodoimidazole 10, and tested as inhibitors of β- and α-glucosidases. Introduction of hydrophobic and flexible substituents, such as in 28 and 29, led to a very strong inhibition of β-glucosidases, with K(i) values for 29 of 1.2 and 0.11 nm against β-glucosidases from almonds and Caldocellum saccharolyticum, respectively. A slow onset of the inhibition was observed for the strongly inhibiting 16, 28-31, 37, and 38. While the introduction of a hydroxymethyl or a phenethyl substituent as in 17 and 30 led to stronger inhibition, the 1'-hydroxyphenethyl derivatives 37 and 38 were weaker inhibitors than 16 and 29. This result is interpreted in the light of a conformational change of the substrate on the way to the transition state. The substituent at C(2) has only a moderate influence on the selectivity of the inhibition of two β- and one α-glucosidases, increasing it by a maximal factor of ca. 10 (16), or decreasing it by a maximal factor of ca. 15 (37).
