title: Structure-activity relationships in a series of C2-substituted gluco-configured tetrahydroimidazopyridines as β-glucosidase inhibitors.
abstract: 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 (K(i)=0.64 nM) and 5 (K(i)=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.
authors.affiliation: College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Tiehai
authors.initials: T
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D027861:Prunus / Q000201:enzymology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D010936:Plant Extracts; D011725:Pyridines; D001617:beta-Glucosidase