dc.creator | Bokor E., Kyriakis E., Solovou T.G.A., Koppány C., Kantsadi A.L., Szabó K.E., Szakács A., Stravodimos G.A., Docsa T., Skamnaki V.T., Zographos S.E., Gergely P., Leonidas D.D., Somsák L. | en |
dc.date.accessioned | 2023-01-31T07:38:58Z | |
dc.date.available | 2023-01-31T07:38:58Z | |
dc.date.issued | 2017 | |
dc.identifier | 10.1021/acs.jmedchem.7b01056 | |
dc.identifier.issn | 00222623 | |
dc.identifier.uri | http://hdl.handle.net/11615/71804 | |
dc.description.abstract | Aryl substituted 1-(β-d-glucosaminyl)-1,2,3-triazoles as well as C-β-d-glucosaminyl 1,2,4-triazoles and imidazoles were synthesized and tested as inhibitors against muscle and liver isoforms of glycogen phosphorylase (GP). While the N-β-d-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-β-d-glucosaminyl derivatives had potent activity, and the best inhibitor was the 2-(β-d-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a Ki value of 143 nM against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the differences between imidazole and 1,2,4-triazole analogues. © 2017 American Chemical Society. | en |
dc.language.iso | en | en |
dc.source | Journal of Medicinal Chemistry | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85034949385&doi=10.1021%2facs.jmedchem.7b01056&partnerID=40&md5=a379c9e0ee780b4db4fcc07884628954 | |
dc.subject | 1 (2' amino 2' deoxy beta dextro glucopyranosyl) 4 (2 naphthyl) 1,2,3 triazole | en |
dc.subject | 1 (2' amino 2' deoxy beta dextro glucopyranosyl) 4 phenyl 1,2,3 triazole | en |
dc.subject | 1,2,3 triazole derivative | en |
dc.subject | 1,2,4 triazole derivative | en |
dc.subject | 2 (2' amino 2' deoxy beta dexro glucopyranosyl) 4(5) (2 naphthyl)imidazole | en |
dc.subject | 2 (2' amino 2' deoxy beta dextro glucopyranosyl) 4(5)phenyl imidazole | en |
dc.subject | 2 (2' amino 2' deoxy beta dextro glucopyranosyl)benzimidazole | en |
dc.subject | 2 (2' deoxy 2' phthalimido 3',4',6' tri o acetyl beta detro glucopyranosyl) 4(5) phenyl imidazole | en |
dc.subject | 2 (2' deoxy 2' phthalimido 3',4',6' tri o acetyl beta dextro glucopyranosyl) 4(5) (2 naphthyl)imidazole | en |
dc.subject | 2 (2' deoxy 2' phthalimido 3',4',6' tri o acetyl beta dextro glucopyranosyl)benzimidazole | en |
dc.subject | 3 (2' amino 2' deoxy beta dextro glucopyranosyl) 5 (2 naphthyl) 1,2,4 triazole | en |
dc.subject | 3 (2' amino 2' deoxy beta dextro glucopyranosyl) 5 phenyl 1,2,4 triazole | en |
dc.subject | ethyl c (2 deoxy 2 phthalimido 3,4,6 tri o acetyl beta dextro glucopyranosyl)formimidate | en |
dc.subject | glucosamine derivative | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | glycosyltransferase inhibitor | en |
dc.subject | heterocyclic compound | en |
dc.subject | imidazole derivative | en |
dc.subject | n (2 deoxy 2 phthalimido 3,4,6 tri o acetyl beta dextro glucopyranosylcarbonyl)benzenethiocarboxamide | en |
dc.subject | n (2 deoxy 2 phthalimido 3,4,6 tri o acetyl beta dextro glucopyranosylcarbonyl)naphthalene 2 thiocarboxamide | en |
dc.subject | unclassified drug | en |
dc.subject | 2-(2'-amino-2'-deoxyglucopyranosyl)-4(5)-(2-naphthyl)imidazole | en |
dc.subject | glucosamine | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | imidazole derivative | en |
dc.subject | triazole derivative | en |
dc.subject | allosteric site | en |
dc.subject | animal tissue | en |
dc.subject | Article | en |
dc.subject | comparative study | en |
dc.subject | competitive inhibition | en |
dc.subject | controlled study | en |
dc.subject | drug potency | en |
dc.subject | drug protein binding | en |
dc.subject | drug synthesis | en |
dc.subject | enzyme inhibition | en |
dc.subject | enzyme kinetics | en |
dc.subject | human | en |
dc.subject | hydrogen bond | en |
dc.subject | Leporidae | en |
dc.subject | ligand binding | en |
dc.subject | muscle | en |
dc.subject | nonhuman | en |
dc.subject | structure activity relation | en |
dc.subject | X ray crystallography | en |
dc.subject | analogs and derivatives | en |
dc.subject | animal | en |
dc.subject | antagonists and inhibitors | en |
dc.subject | enzymology | en |
dc.subject | kinetics | en |
dc.subject | liver | en |
dc.subject | protein domain | en |
dc.subject | skeletal muscle | en |
dc.subject | synthesis | en |
dc.subject | X ray crystallography | en |
dc.subject | Animals | en |
dc.subject | Crystallography, X-Ray | en |
dc.subject | Glucosamine | en |
dc.subject | Glycogen Phosphorylase | en |
dc.subject | Humans | en |
dc.subject | Hydrogen Bonding | en |
dc.subject | Imidazoles | en |
dc.subject | Kinetics | en |
dc.subject | Liver | en |
dc.subject | Muscle, Skeletal | en |
dc.subject | Protein Domains | en |
dc.subject | Rabbits | en |
dc.subject | Structure-Activity Relationship | en |
dc.subject | Triazoles | en |
dc.subject | American Chemical Society | en |
dc.title | Nanomolar Inhibitors of Glycogen Phosphorylase Based on β- D -Glucosaminyl Heterocycles: A Combined Synthetic, Enzyme Kinetic, and Protein Crystallography Study | en |
dc.type | journalArticle | en |