191863-33-9Relevant 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).
Synthesis of gluco-configured tetrahydroimidazopyridine-2-phosphonate- derived lipids, potential glucosyl transferase inhibitors
Billault, Isabelle,Vasella, Andrea
, p. 1137 - 1149 (2007/10/03)
The analogues 1-3 of dolichol monophosphatidyl β-D-glucose have been prepared as potential inhibitors of the glucosyl transferase Alg10p, Pd(PPh3)4-catalysed phosphonylation of the iodoimidazole 4 with diethyl, dimethyl, and diphenyl
Structure-activity relations for imidazo-pyridine-type inhibitors of β-D-glucosidases
Granier, Thierry,Panday, Narendra,Vasella, Andrea
, p. 979 - 987 (2007/10/03)
The triazole 7 and the known gluco- and manno-configurated imidazoles 10 and 11 have been prepared by annulation of the azole ring to the aldonothiolactam 14 in a Hg(OAc)2-promoted reaction with either hydrazinecarbaldehyde or aminoacetaldehyde dimethyl acetal. Depending upon the reaction conditions, the synthesis of the imidazoles yielded mostly the gluco-imidazole 19 or a mixture of the gluco/manno epimers 19/20. In contrast to the triazole 4, the isomeric triazole 7 proved a good inhibitor of retaining β-glucosidases from sweet almonds and from Caldocellum saccharolyticum. This observation and the qualitative correlation between basicity and inhibitory power of the tetrahydropyridoazoles provide further evidence for the hypothesis of the 'lateral protonation' of glycosides by (some) retaining β-glucosidases.
