Cited by 185Carbohydrate Chemistry and SynthesisGlycogen Storage Diseases and MyoclonusHeterocyclic Compound Synthesis and Bioactivity

The DOI matches its Crossref record.

Glucose Analog Inhibitors of Glycogen Phosphorylases as Potential Antidiabetic Agents: Recent Developments

Open access

Somsak, Laszlo, Nagy, Veronika, Hadady, Zsuzsa, Docsa, Tibor, Gergely, Pal·2003·Current Pharmaceutical Design

DOI 10.2174/1381612033454919

Open this paper in CoChat — free account

Abstract

Diabetes is among the largest contributors to global mortality through its long term complications. The worldwide epidemic of type 2 diabetes has been stimulating the quest for new concepts and targets for the treatment of this incurable disease. A new target is glycogen phosphorylase (GP), the main regulatory enzyme in the liver responsible for the control of blood glucose levels. One of several approaches to influence the action of GP is the use of glucose derivatives as active site inhibitors. This field of research commenced 10-15 years ago and, due to joint efforts in computer aided molecular design, organic synthesis, protein crystallography, and biological assays, resulted in glucopyranosylidene-spiro-hydantoin 16 (K(i) = 3-4 micro M) as the most efficient glucose analog inhibitor of GP of that time. The present paper surveys the recent developments of this field achieved mainly in the last five years: the synthesis and evaluation of glucopyranosylidene-spiro-thiohydantoin 18 (K(i) = 5 micro M) which has proven equipotent with 16, and is available in gram amounts; furanosylidene- and xylopyranosylidene-spiro-(thio)hydantoins whose ineffectiveness (K(i) > 10 mM) confirmed the high specificity of the catalytic site of GP towards the D-glucopyranosyl unit; "open" hydantoins like methyl N-(1-carboxamido-D-glucopyranosyl)carbamate 37 (K(i) = 16 micro M) and N-acyl-N'-(beta-D-glucopyranosyl)ureas among them the to date best glucose analog inhibitor N-(2-naphthoyl)-N'-(beta-D-glucopyranosyl)urea (35, K(i) = 0.4 micro M) which can also bind to the so-called new allosteric site of GP; C-(beta-D-glucopyranosyl)heterocycles (tetrazole, 1,3,4-oxadiazoles, benzimidazole (K(i) = 11 micro M), and benzothiazole). Iminosugars like isofagomine (45, IC(50) = 0.7 micro M), noeuromycin (53, IC(50) = 4 micro M), and azafagomine (54, IC(50) = 13.5 micro M) also bind strongly to the active site of GP, however, substitution on the nitrogens makes the binding weaker. The natural product five-membered iminosugar DAB (56) exhibited IC(50) approximately 0.4-0.5 micro M. Azoloperhydropyridines which can be regarded iminosugar-annelated heterocycles show moderate inhibition of GP: nojiritetrazole 12 (K(i) = 53 micro M) is the best inhibitor and fewer nitrogens in the five-membered ring weakens the binding. Physiological investigations have been carried out with N-acetyl-beta-D-glucopyranosylamine 6, spiro-thiohydantoin 18, isofagomine 45, and DAB 56 to underline the potential use of these compounds in the treatment of type 2 diabetes. Computational methods suggest to synthesize further anomerically bifunctional glucose derivatives which may be good inhibitors of GP.

Integrity signals

Registry

Crossref · 10.2174/1381612033454919

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Sorted by citations

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules
Kirk, K. L. (2006) · Journal of Fluorine Chemistry · doi:10.1016/j.jfluchem.2006.06.007 · Cited by 912
The Polar Hydrophobicity of Fluorinated Compounds
Biffinger, J. C., Kim, H. W., & DiMagno, S. G. (2004) · ChemBioChem · doi:10.1002/cbic.200300910 · Cited by 485
Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy
Zois, C. E., & Harris, A. L. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1377-9 · Cited by 267
Crataegus pinnatifida: Chemical Constituents, Pharmacology, and Potential Applications
Jia-qi, W., Peng, W., Qin, R., et al. (2014) · Molecules · doi:10.3390/molecules19021685 · Cited by 178
“concentrations in type II diabetes [87,88].”
Tactics and strategies for the synthesis of iminosugar C-glycosides: a review
Compain, P., Chagnault, V., & Martin, O. R. (2009) · Tetrahedron Asymmetry · doi:10.1016/j.tetasy.2009.03.031 · Cited by 167
Sugar-mimicking glycosidase inhibitors: bioactivity and application
Asano, N. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8522-3 · Cited by 134
Targeted drugs by olefin metathesis: piperidine-based iminosugars
Drăguţan, I., Drăguţan, V., & Demonceau, A. (2011) · RSC Advances · doi:10.1039/c1ra00910a · Cited by 105
Glycogen metabolism in cancer
Zois, C. E., Favaro, E., & Harris, A. L. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.09.001 · Cited by 102
Pentacyclic triterpenes. Part 2: Synthesis and biological evaluation of maslinic acid derivatives as glycogen phosphorylase inhibitors
Wen, X., Zhang, P., Liu, J., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.10.014 · Cited by 102
Synthesis and biological activity of naturally occurring α-glucosidase inhibitors
Wardrop, D. J., & Waidyarachchi, S. L. (2010) · Natural Product Reports · doi:10.1039/b914958a · Cited by 98
Pentacyclic triterpenes. Part 3: Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of glycogen phosphorylase
Chen, J., Liu, J., Zhang, L., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.03.009 · Cited by 96
Kinetic and crystallographic studies on 2‐(β‐D‐glucopyranosyl)‐5‐methyl‐1, 3, 4‐oxadiazole, ‐benzothiazole, and ‐benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site
Chrysina, E. D., Kosmopoulou, M. N., Tiraidis, C., Kardakaris, R., Bischler, N., Leonidas, D. D., Hadady, Z., Somsák, L., Docsa, T., Gergely, P., et al. (2005) · Protein Science · doi:10.1110/ps.041216105 · Cited by 89
“…the basis of information derived from the crystal structure of T-state GPb– -D-glucose complex (Martin et al. 1991; Watson et al. 1994, 1995; Bichard et al. 1995; Oikonomakos et al. 1995, 2002a,b; Gregoriou et al. 1998; Somsák et al. 2001, 2003; Chrysina et al. 2003, 2004; Györgydeák et al. 2004).”
BackgroundSelf-citation
ABO(H) Blood Group A and B Glycosyltransferases Recognize Substrate via Specific Conformational Changes
Alfaro, J. A., Zheng, R. B., Persson, M., Letts, J. A., Polakowski, R., Bai, Y., Borisova, S. N., Seto, N. O. L., Lowary, T. L., Palcic, M. M., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708669200 · Cited by 87
Glycogen Phosphorylase Inhibition in Type 2 Diabetes Therapy
Baker, D. J., Timmons, J. A., & Greenhaff, P. L. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2453 · Cited by 87
“Great interest has been generated regarding the potential benefits of GPis for the treatment of type 2 diabetes because their mode of action may avoid hyperglycemic episodes (8,9,11,12,33).”
Background
Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition
Goyard, D., Kónya, B., Chajistamatiou, A. S., Chrysina, E. D., Leroy, J., Balzarin, S., Tournier, M., Tousch, D., Petit, P., Duret, C., et al. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.12.004 · Cited by 86
Self-citation
Synthesis of 1-(d-glucopyranosyl)-1,2,3-triazoles and their evaluation as glycogen phosphorylase inhibitors
Bokor, É., Docsa, T., Gergely, P., & Somsák, L. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.12.043 · Cited by 85
Self-citation
1,3-Dipolar cycloaddition reactions on carbohydrate-based templates: synthesis of spiro-isoxazolines and 1,2,4-oxadiazoles as glycogen phosphorylase inhibitors
Benltifa, M., Vidal, S., Gueyrard, D., Goekjian, P. G., Msaddek, M., & Praly, J. (2006) · Tetrahedron Letters · doi:10.1016/j.tetlet.2006.06.058 · Cited by 85
Glucose derived inhibitors of glycogen phosphorylase
Somsák, L. (2010) · Comptes Rendus Chimie · doi:10.1016/j.crci.2010.09.004 · Cited by 81
Self-citation
Characterization of 1,4‐dideoxy‐1,4‐imino‐ d ‐arabinitol (DAB) as an inhibitor of brain glycogen shunt activity
Walls, A. B., Sickmann, H. M., Brown, A. M., Bouman, S. D., Ransom, B. R., Schousboe, A., & Waagepetersen, H. S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05250.x · Cited by 73
“1,4-Dideoxy-1,4-imino-D-arabinitol which structurally resembles glucose in regard to the positioning of the hydroxyl groups (Somsak et al. 2003) is a potential substrate for the glucose transporter, and consequently this was tested by measuring influx and subsequent phosphorylation of…”
Background
In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures
Kuriyama, C., Kamiyama, O., Ikeda, K., Sanae, F., Kato, A., Adachi, I., Imahori, T., Takahata, H., Okamoto, T., & Asano, N. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.06.026 · Cited by 69
Asymmetric synthesis of 1-deoxynojirimycin and its congeners from a common chiral building block
Takahata, H., Banba, Y., Sasatani, M., et al. (2004) · Tetrahedron · doi:10.1016/j.tet.2004.06.112 · Cited by 67
A New Route to Diverse 1-Azasugars fromN-Boc-5-hydroxy-3-piperidene as a Common Building Block
Ouchi, H., Mihara, Y., & Takahata, H. (2005) · The Journal of Organic Chemistry · doi:10.1021/jo050519j · Cited by 66
A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of selected traditional sudanese plants with anti-diabetic potential
Hilmi, Y., Abushama, M., Abdalgadir, H., et al. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-149 · Cited by 65
Iminosugars as Potential Inhibitors of Glycogenolysis: Structural Insights into the Molecular Basis of Glycogen Phosphorylase Inhibition
Oikonomakos, N. G., Tiraidis, C., Leonidas, D. D., Zographos, S. E., Kristiansen, M., Jessen, C. U., Nørskov‐Lauritsen, L., & Agius, L. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060496g · Cited by 65
Glycogen metabolism and the homeostatic regulation of sleep
Petit, J.-M., Burlet-Godinot, S., Magistretti, P. J., & Allaman, I. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9629-x · Cited by 79
“In vitro, DAB potently inhibits GP in different preparations (Andersen andWestergaard 2002; Somsak et al. 2003) including brain tissue homogenates (IC50≈0.”
Background
Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding
Zhang, F., Xu, X., Zhou, B. Z., He, Z., & Zhai, Q. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027553 · Cited by 62
“Among the 28 downregulated genes, glycogen phosphorylase (Pygl) catalyzes the ratelimiting step in the degradation of glycogen in animals [14], and glycogen phosphorylase inhibitors has been proposed as potential antidiabetic agents [45].”
Background
In Search of Glycogen Phosphorylase Inhibitors: 5‐Substituted 3‐C‐Glucopyranosyl‐1,2,4‐oxadiazoles from β‐ D ‐Glucopyranosyl Cyanides upon Cyclization of O‐Acylamidoxime Intermediates
Benltifa, M., Vidal, S., Fenêt, B., et al. (2006) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200600073 · Cited by 62
Self-citation
Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy-β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase
Györgydeák, Z., Hadady, Z., Felföldi, N., et al. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.07.013 · Cited by 61
Self-citation
Pentacyclic triterpenes. Part 5: Synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases
Wen, X., Xia, J., Cheng, K., Zhang, L., Zhang, P., Liu, J., Zhang, L., Ni, P., & Sun, H. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.08.057 · Cited by 58
C-Branched Iminosugars: α-Glucosidase Inhibition by Enantiomers of isoDMDP, isoDGDP, and isoDAB– l -isoDMDP Compared to Miglitol and Miglustat
Jenkinson, S. F., Best, D., Saville, A. W., Mui, J., Martínez, R. F., Nakagawa, S., Kunimatsu, T., Alonzi, D. S., Butters, T. D., Norez, C., et al. (2013) · The Journal of Organic Chemistry · doi:10.1021/jo4005487 · Cited by 49
Pyrrolizidine Alkaloids
Tamariz, J., Burgueño‐Tapia, E., Vazquez, M. A., & Delgado, F. (2018) · The Alkaloids. Chemistry and biology/The alkaloids. Chemistry and biology · doi:10.1016/bs.alkal.2018.03.001 · Cited by 54
Effect of glucopyranosylidene-spiro-thiohydantoin on glycogen metabolism in liver tissues of streptozotocin-induced and obese diabetic rats
Gergely, P. (2011) · Molecular Medicine Reports · doi:10.3892/mmr.2011.464 · Cited by 47
Self-citation
Glycogen phosphorylase inhibition as a therapeutic target: a review of the recent patent literature
Baker, D. J., Greenhaff, P. L., & Timmons, J. A. (2006) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.16.4.459 · Cited by 45
“Therefore, unsurprisingly, glucose analogues have been shown to be effective inhibitors of GP [34-46].”
Background
Differential Recognition of the Type I and II H Antigen Acceptors by the Human ABO(H) Blood Group A and B Glycosyltransferases
Letts, J. A., Rose, N. L., Fang, Y. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507620200 · Cited by 44
Metathesis access to monocyclic iminocyclitol-based therapeutic agents
Drăguţan, I., Drăguţan, V., Mitan, C. I., Vosloo, H. C. M., Delaude, L., & Demonceau, A. (2011) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.7.81 · Cited by 43
A General Approach to the Synthesis of 1-Deoxy- l -iminosugars
Guaragna, A., D’Errico, S., D’Alonzo, D., et al. (2007) · Organic Letters · doi:10.1021/ol7014847 · Cited by 42
Synthetic, enzyme kinetic, and protein crystallographic studies of C -β- d -glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase
Kantsadi, A. L., Bokor, É., Kun, S., Stravodimos, G. A., Chatzileontiadou, D. S. M., Leonidas, D. D., Juhász‐Tóth, É., Szakács, A., Batta, G., Docsa, T., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.06.049 · Cited by 42
“O-Perbenzylated glucosyl acetylene41 19 was cross-coupled with N-tosyl-2-iodoaniline (20) and cyclized to indole 2140 in one step.”
BackgroundMethodInfluentialSelf-citation
Facile Aza‐Claisen Rearrangement of Glycals: Application in the Synthesis of 1‐Deoxy‐ L ‐iminosugars
Gupta, P., & Vankar, Y. D. (2009) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200801301 · Cited by 42
Synthesis, structural elucidation, antioxidant, CT-DNA binding and molecular docking studies of novel chloroquinoline derivatives: Promising antioxidant and anti-diabetic agents
Murugavel, S., Stephen, C. S. J. P., Subashini, R., et al. (2017) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2017.05.043 · Cited by 40
Identification, Synthesis, and Characterization of New Glycogen Phosphorylase Inhibitors Binding to the Allosteric AMP Site
Kristiansen, M., Andersen, B., Iversen, L. F., & Westergaard, N. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm031121n · Cited by 40
General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)
Goujon, J., Gueyrard, D., Compain, P., et al. (2005) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.12.043 · Cited by 39
Amino-functionalized iminocyclitols: synthetic glycomimetics of medicinal interest
Harit, V. K., & Ramesh, N. G. (2016) · RSC Advances · doi:10.1039/c6ra23513a · Cited by 38
Iminosugars as a new class of cholinesterase inhibitors
Decroocq, C., Stauffert, F., Pamlard, O., Oulaïdi, F., Gallienne, E., Martin, O. R., Guillou, C., & Compain, P. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.12.071 · Cited by 37
Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase
Nagy, V., Benltifa, M., Vidal, S., et al. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.05.080 · Cited by 36
Self-citation
Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies
Liang, Z. T., Zhang, L., Li, L., Liu, J., Li, H., Zhang, L., Chen, L., Cheng, K., Zheng, M., Wen, X., et al. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.02.053 · Cited by 35
Efficient and Stereodivergent Syntheses of D ‐ and L ‐Fagomines and Their Analogues
Kumari, N., Reddy, B. G., & Vankar, Y. D. (2008) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200800796 · Cited by 35
Analogues of insulin secretagogue (2S,3R,4S)-4-hydroxyisoleucine: synthesis by 1,3-dipolar cycloaddition reactions of chiral nitrones to alkenes
Aouadi, K., Jeanneau, E., Msaddek, M., et al. (2008) · Tetrahedron Asymmetry · doi:10.1016/j.tetasy.2008.04.006 · Cited by 34
The crystal structure of human muscle glycogen phosphorylase a with bound glucose and AMP: An intermediate conformation with T‐state and R‐state features
Lukacs, C., Oikonomakos, N. G., Crowther, R. L., Hong, L., Kammlott, R. U., Levin, W., Li, S., Liu, C., Lucas‐McGady, D., Pietranico, S., et al. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20939 · Cited by 34
Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis
Esposito, A., D’Alonzo, D., Fenza, M. D., Gregorio, E. D., Tamanini, A., Lippi, G., Dechecchi, M. C., & Guaragna, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093353 · Cited by 33
Synthesis of new β-1-C-alkylated imino-l-iditols: A comparative study of their activity as β-glucocerebrosidase inhibitors
Schönemann, W., Gallienne, E., Compain, P., et al. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.02.027 · Cited by 32
Effects of eugenol-reduced clove extract on glycogen phosphorylase b and the development of diabetes in db/db mice
Sanae, F., Kamiyama, O., Ikeda‐Obatake, K., et al. (2013) · Food & Function · doi:10.1039/c3fo60514k · Cited by 32
An expeditious one-pot synthesis of 1,6-dideoxy-N-alkylated nojirimycin derivatives and their inhibitory effects on the secretion of IFN-γ and IL-4
Zhou, J., Zhang, Y., Zhou, X., Zhou, J., Zhang, L., Ye, X., & Zhang, X. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.11.036 · Cited by 32
Novel design principle validated: Glucopyranosylidene-spiro-oxathiazole as new nanomolar inhibitor of glycogen phosphorylase, potential antidiabetic agent
Somsák, L., Nagy, V., Vidal, S., Czifrák, K., Berzsényi, E., & Praly, J. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.08.052 · Cited by 32
Self-citation
A new asymmetric synthetic route to substituted piperidines
Reddy, M. S., Narender, M., & Rao, K. R. (2006) · Tetrahedron · doi:10.1016/j.tet.2006.10.073 · Cited by 31
A new synthetic access to bicyclic polyhydroxylated alkaloid analogues from pyranosides
Wang, N., Zhang, L., & Ye, X. (2010) · Organic & Biomolecular Chemistry · doi:10.1039/b923180c · Cited by 31
Probing multivalency for the inhibition of an enzyme: glycogen phosphorylase as a case study
Cecioni, S., Argintaru, O.-A., Docsa, T., Gergely, P., Praly, J., & Vidal, S. (2008) · New Journal of Chemistry · doi:10.1039/b812540f · Cited by 31
Self-citation
In the Search of Glycogen Phosphorylase Inhibitors: Synthesis of C‐ D ‐Glycopyranosylbenzo(hydro)quinones – Inhibition of and Binding to Glycogen Phosphorylase in the Crystal
He, L., Zhang, Y. Z., Tanoh, M., et al. (2006) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200600548 · Cited by 31
Total synthesis of (+)-valienamine and (−)-1-epi-valienamine via a highly diastereoselective allylic amination of cyclic polybenzyl ether using chlorosulfonyl isocyanate
Li, Q. R., Kim, S. I., Park, S. J., et al. (2013) · Tetrahedron · doi:10.1016/j.tet.2013.09.098 · Cited by 30
Inhibition of human salivary α-amylase by glucopyranosylidene-spiro-thiohydantoin
Gyémánt, G., Kandra, L., Nagy, V., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.119 · Cited by 30
Self-citation
Expeditious Synthesis of a Common Intermediate of l -1-Deoxyallonojirimycin and l -1-Deoxymannojirimycin
Ferreira, F., Botuha, C., Chemla, F., et al. (2009) · The Journal of Organic Chemistry · doi:10.1021/jo802757f · Cited by 30
Synthesis of Thiohydantoin-Castanospermine Glycomimetics as Glycosidase Inhibitors
Aguilar‐Moncayo, M., Mellet, C. O., Fernández, J. M. G., & García‐Moreno, M. I. (2009) · The Journal of Organic Chemistry · doi:10.1021/jo900231b · Cited by 30
Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars
Reddy, Y. S., Kancharla, P. K., Roy, R., & Vankar, Y. D. (2012) · Organic & Biomolecular Chemistry · doi:10.1039/c2ob06851f · Cited by 30
Crystallographic and computational studies on 4‐phenyl‐N‐(β‐ D ‐glucopyranosyl)‐1H‐1,2,3‐triazole‐1‐acetamide, an inhibitor of glycogen phosphorylase: Comparison with α‐ D ‐glucose, N‐acetyl‐β‐ D ‐glucopyranosylamine and N‐benzoyl‐N′‐β‐ D ‐glucopyranosyl urea binding
Alexacou, K.-M., Hayes, J. M., Tiraidis, C., Zographos, S. E., Leonidas, D. D., Chrysina, E. D., Archontis, G., Oikonomakos, N. G., Paul, J. V., Varghese, B., et al. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21837 · Cited by 30
“Glucosyltriazolylacetamide is accommodated in the catalytic site of the enzyme and the glucopyranose interacts in a manner similar to that observed in the GPb-aD-glucose complex, while the substituent group in the b-posi- tion of the C1 atom makes additional hydrogen bonding and van der Waals interactions to the prote…”
BackgroundInfluential
Design, synthesis and biological evaluation of bicyclic iminosugar hybrids: conformational constraint as an effective tool for tailoring the selectivity of α-glucosidase inhibitors
Arora, I., Kashyap, V. K., Singh, A., Dasgupta, A., Kumar, B. N., & Shaw, A. K. (2014) · Organic & Biomolecular Chemistry · doi:10.1039/c4ob00486h · Cited by 29
First Total Synthesis of 1-O-β- d -Glucopyranosyl-5-deoxyadenophorine and Its Aglycon Congener: Determination of the Absolute Configuration
Felpin, F., Boubekeur, K., & Lebreton, J. (2004) · The Journal of Organic Chemistry · doi:10.1021/jo035522m · Cited by 29
Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents
Трифонов, Р. Е., & Ostrovskii, V. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417190 · Cited by 28
Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient
Rochester, C. D. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i3.305 · Cited by 29
Synthesis of Aminocyclitols and Trihydroxylated Indolizidinone from a D ‐Mannitol‐Derived Common Building Block
Gupta, P., Pal, A. P. J., Reddy, Y. S., et al. (2010) · European Journal of Organic Chemistry · doi:10.1002/ejoc.201001171 · Cited by 28
Preparation of a Stable Bicyclic Aziridinium Ion and Its Ring Expansion toward Piperidines and Azepanes
Choi, J., Yadav, N. N., & Ha, H. (2017) · Asian Journal of Organic Chemistry · doi:10.1002/ajoc.201700080 · Cited by 28
Stereocontrolled Access to Orthogonally Protected anti,anti-4-Aminopiperidine-3,5-diols through Chemoselective Reduction of Enantiopure β-Lactam Cyanohydrins
Alcaide, B., Almendros, P., Cabrero, G., et al. (2007) · The Journal of Organic Chemistry · doi:10.1021/jo701452a · Cited by 28
Glycosidase Inhibitors: Structure, Activity, Synthesis, and Medical Relevance
Bols, M., López, Ó., & Ortega‐Caballero, F. (2007) · Elsevier eBooks · doi:10.1016/b978-044451967-2/00100-8 · Cited by 30
Iminosugar C-Nitromethyl Glycoside: Stereoselective Synthesis of Isoxazoline and Isoxazole-Fused Bicyclic Iminosugars
Prasad, S. S., & Baskaran, S. (2018) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.7b02803 · Cited by 26
Sugar amino acids at the anomeric position of carbohydrates: synthesis of spirocyclic amino acids of 6-deoxy-l-lyxofuranose
Blériot, Y., Simone, M. I., Wormald, M. R., et al. (2006) · Tetrahedron Asymmetry · doi:10.1016/j.tetasy.2006.07.027 · Cited by 26
Synthesis of N-substituted iminosugar derivatives and their immunosuppressive activities
Zhang, G., Chen, C., Xiong, Y., et al. (2010) · Carbohydrate Research · doi:10.1016/j.carres.2010.01.021 · Cited by 26
Spectroscopic investigation (FT-IR, FT-Raman), HOMO–LUMO, NBO analysis and molecular docking study of 4-chlorophenyl quinoline-2-carboxylate
Fazal, E., Panicker, C. Y., Varghese, H. T., et al. (2015) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2015.01.089 · Cited by 26
Saponin as regulator of biofuel: implication for ethnobotanical management of diabetes
Elekofehinti, O. O., Omotuyi, O. I., Kamdem, J. P., Ejelonu, O. C., Olher, V. G. A., Adanlawo, I. G., & da Rocha, J. B. T. (2014) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-014-0325-4 · Cited by 27
“The inhibition of glycogen phosphorylase has been proposed as one method for treating type 2 diabetes [104] since glucose production in the liver has been shown to increase in type 2 diabetes patients [81].”
Method
Preliminary Studies on the Transformation of Nitrosugars into Branched Chain Iminosugars: Synthesis of 1,4-Dideoxy-4-C-hydroxymethyl- 1,4-imino-pentanols
Otero, J. M., Soengas, R. G., Estevez, J. C., et al. (2007) · Organic Letters · doi:10.1021/ol062887v · Cited by 26
Straightforward carbamoylation of nucleophilic compounds employing organic azides, phosphines, and aqueous trialkylammonium hydrogen carbonate
Yagodkin, A., Löschcke, K., Weisell, J., et al. (2010) · Tetrahedron · doi:10.1016/j.tet.2010.01.017 · Cited by 26
Rapid and practical synthesis of (−)-1-deoxyaltronojirimycin
Karjalainen, O. K., & Koskinen, A. M. P. (2010) · Organic & Biomolecular Chemistry · doi:10.1039/c0ob00747a · Cited by 25
A Facile Synthesis of Lentiginosine Analogues Based on a Highly Regio‐ and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate
Kim, I. S., Li, Q. R., Dong, G. R., Kim, Y. C., Hong, Y. J., Lee, M., Chi, K., Oh, J. S., & Jung, Y. H. (2010) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200901443 · Cited by 25
Uncatalyzed One-Pot Synthesis of Highly Substituted Pyridazines and Pyrazoline-Spirooxindoles via Domino SN/Condensation/Aza-ene Addition Cyclization Reaction Sequence
Zohreh, N., & Alizadeh, A. (2013) · ACS Combinatorial Science · doi:10.1021/co400005y · Cited by 25
Stereocontrolled synthesis of thiohydantoin spironucleosides from sugar spiroacetals
Fuentes, J. A., Salameh, B. A. B., Pradera, M. Á., et al. (2005) · Tetrahedron · doi:10.1016/j.tet.2005.09.128 · Cited by 25
Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs
Oikonomakos, N. G., Kosmopoulou, M. N., Chrysina, E. D., Leonidas, D. D., Kostas, I. D., Wendt, K. U., Klabunde, T., & Defoßa, E. (2005) · Protein Science · doi:10.1110/ps.051432405 · Cited by 25
“1) have been identified as specific targets for inhibitor binding (Somsák et al. 2001, 2003; Treadway et al. 2001; Oikonomakos 2002; Kurukulasuriya et al. 2003).”
Background
Stereodivergent Access to Polyhydroxylated 10-Azabicyclo[4.3.1]decanes as New Calystegine Analogues
Chagnault, V., Compain, P., Lewiński, K., et al. (2009) · The Journal of Organic Chemistry · doi:10.1021/jo900235d · Cited by 24
Tethered derivatives of d-glucose and pentacyclic triterpenes for homo/heterobivalent inhibition of glycogen phosphorylase
Cheng, K., Liu, J., Sun, H., Bokor, É., Czifrák, K., Kónya, B., Tóth, M., Docsa, T., Gergely, P., & Somsák, L. (2010) · New Journal of Chemistry · doi:10.1039/b9nj00602h · Cited by 23
Self-citation
Assessment of synthetic methods for the preparation of N-β-d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds
Somsák, L., Felföldi, N., Kónya, B., et al. (2008) · Carbohydrate Research · doi:10.1016/j.carres.2008.01.045 · Cited by 23
Self-citation
New synthetic approaches to sugar ureas. Access to ureido-β-cyclodextrins
López, Ó., Maza, S., Maya, I., et al. (2005) · Tetrahedron · doi:10.1016/j.tet.2005.07.041 · Cited by 23
Synthesis of cyclic hydrazines by ring-closing metathesis of dienes and enynes tethered by an N–N bond
Tae, J., & Hahn, D. (2004) · Tetrahedron Letters · doi:10.1016/j.tetlet.2004.03.075 · Cited by 23
Crystallographic studies on two bioisosteric analogues, N-acetyl-β-d-glucopyranosylamine and N-trifluoroacetyl-β-d-glucopyranosylamine, potent inhibitors of muscle glycogen phosphorylase
Anagnostou, E., Kosmopoulou, M. N., Chrysina, E. D., et al. (2005) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.08.010 · Cited by 23
Self-citation
Divergent Synthesis of 4-epi-Fagomine, 3,4-Dihydroxypipecolic Acid, and a Dihydroxyindolizidine and Their β-Galactosidase Inhibitory and Immunomodulatory Activities
Kumar, K. S. A., Rathee, J. S., Subramanian, M., & Chattopadhyay, S. (2013) · The Journal of Organic Chemistry · doi:10.1021/jo400448p · Cited by 23
Diastereoselective Synthesis of 1-Deoxygalactonojirimycin, 1-Deoxyaltronojirimycin, and N-Boc-(2S,3S)-3-Hydroxypipecolic Acid via Proline Catalyzed α-Aminoxylation of Aldehydes
Chacko, S., & Ramapanicker, R. (2015) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.5b00424 · Cited by 21
An Isofagomine Analogue with an Amidine at the Pseudoanomeric Position
Lindbäck, E., López, Ó., Fernández‐Bolaños, J. G., et al. (2011) · Organic Letters · doi:10.1021/ol200942g · Cited by 21
A facile access to ureido sugars. Synthesis of urea-bridged β-cyclodextrins
Maya, I., López, Ó., Maza, S., et al. (2003) · Tetrahedron Letters · doi:10.1016/j.tetlet.2003.09.140 · Cited by 21
Crystallographic Studies on α- and β-D-glucopyranosyl Formamide Analogues, Inhibitors of Glycogen Phosphorylase
Chrysina, E. D., Oikonomakos, N. G., Zographos, S. E., et al. (2003) · Biocatalysis and Biotransformation · doi:10.1080/10242420310001614360 · Cited by 21
Self-citation
N-Alkyl-1,5-dideoxy-1,5-imino-l-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines
Zhou, J. E., Negi, A., Mirallai, S. I., Warta, R., Herold‐Mende, C. C., Carty, M. P., Ye, X.-S., & Murphy, P. V. (2018) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2018.12.003 · Cited by 19
“These include glycosidases, glycosyltransferases [1,2], glycogen phosphorylases [3], nucleoside-processing enzymes [4], a sugar nucleotide mutase [5,6], metalloproteinases [7] and others [8].”
Background
A stereodivergent approach to 1-deoxynojirimycin, 1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives
Boucheron, C., Compain, P., & Martin, O. R. (2006) · Tetrahedron Letters · doi:10.1016/j.tetlet.2006.02.157 · Cited by 20
Analysis of the Protein Binding Sites for Thiamin and Its Derivatives to Elucidate the Molecular Mechanisms of the Noncoenzyme Action of Thiamin (Vitamin B1)
Bunik, V. I., & Aleshin, V. A. (2017) · Studies in natural products chemistry · doi:10.1016/b978-0-444-63930-1.00011-9 · Cited by 20
One-pot synthesis of 2-C-glycosylated benzimidazoles from the corresponding methanal dimethyl acetals
Vojtech, M., Petrušová, M., Sláviková, E., et al. (2006) · Carbohydrate Research · doi:10.1016/j.carres.2006.10.019 · Cited by 20
GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review
De Masi, R., & Orlando, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137373 · Cited by 20
“This modification confers a particularly high affinity for the α-glucosidase enzyme inhibition, resulting in a clinically relevant anti-diabetic effect [230,231].”
Background
Anomer‐Selective Glycosidase Inhibition by 2‐ N ‐Alkylated 1‐Azafagomines
López, Ó., & Bols, M. (2007) · ChemBioChem · doi:10.1002/cbic.200700012 · Cited by 19

Authors: Somsak, L., Nagy, V., Hadady, Z., Docsa, T., & Gergely, P.
Affiliations: University of Debrecen (HU)
Venue: Current Pharmaceutical Design
Publisher: Bentham Science Publishers Ltd.
Published: 2003-06-01
Volume: 9
Issue: 15
Pages: 1177-1189
ISSN: 1381-6128 (ISSN-L)
DOI: 10.2174/1381612033454919
OpenAlex: W2122174215
Cited by: 185
References: 0
Citations by year: 2026: 1 · 2025: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 14 · 2013: 10 · 2012: 7
FWCI: 9.40
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Current Pharmaceutical Design (publishedVersion)
PubMed (publishedVersion)
University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
Keywords: glycogen phosphorylase, antidiabetic drugs, type 2 diabetes, hydantoin derivatives, allosteric site, iminosugars, isofagomine, benzothiazole, benzimidazole, 1,3,4-oxadiazoles, tetrazoles, enzyme inhibition
MeSH terms: Animals, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Glucose, Humans, Hypoglycemic Agents, Models, Molecular, Molecular Structure, Glycogen Phosphorylase

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Glucose Analog Inhibitors of Glycogen Phosphorylases as Potential Antidiabetic Agents: Recent Developments

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Citations

Cited by

Related

Metadata

Record

About these checks