imino pyranoses

Summary

Summary: Six-carbon pyranose sugars in which the OXYGEN is replaced by a NITROGEN atom.

Top Publications

  1. Steet R, Chung S, Wustman B, Powe A, Do H, Kornfeld S. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc Natl Acad Sci U S A. 2006;103:13813-8 pubmed
    ..These findings provide support for the possible use of active-site inhibitors in the treatment of some forms of Gaucher disease. ..
  2. Lieberman R, Wustman B, Huertas P, Powe A, Pine C, Khanna R, et al. Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat Chem Biol. 2007;3:101-7 pubmed
    ..The design of small molecules that stabilize substrate-bound conformations of mutant proteins may be a general therapeutic strategy for diseases caused by protein misfolding and mistrafficking. ..
  3. Lieberman R, D Aquino J, Ringe D, Petsko G. Effects of pH and iminosugar pharmacological chaperones on lysosomal glycosidase structure and stability. Biochemistry. 2009;48:4816-27 pubmed publisher
    ..Taken together, these results provide insight into how GCase and alpha-Gal A are thermodynamically stabilized by iminosugars and suggest strategies for the development of new pharmacological chaperones for lysosomal storage disorders. ..
  4. Nishimura Y. Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological activity and therapeutic potential. J Antibiot (Tokyo). 2009;62:407-23 pubmed publisher
  5. Murray B, Takayama S, Schultz J, Wong C. Mechanism and specificity of human alpha-1,3-fucosyltransferase V. Biochemistry. 1996;35:11183-95 pubmed
    ..The role of charge and distance in the synergistic inhibitory effect by the combination of GDP, an aza sugar, and the acceptor sugar was probed. A mechanism for fucosyl transfer incorporating these findings is proposed and discussed. ..
  6. Brown A, Sickmann H, Fosgerau K, Lund T, Schousboe A, Waagepetersen H, et al. Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res. 2005;79:74-80 pubmed
    ..The CAP area declined more rapidly when glycogen metabolism was inhibited by isofagomine, explicitly showing an important physiological role for glycogen metabolism during neural activity. ..
  7. Padró M, Castillo J, Gómez L, Joglar J, Clapés P, de Bolos C. Cytotoxicity and enzymatic activity inhibition in cell lines treated with novel iminosugar derivatives. Glycoconj J. 2010;27:277-85 pubmed publisher
    ..Our results indicated that the length of the alkyl chain linked to the iminosugars determine their cytotoxicity as well as the inhibitory effect on the enzymatic activities of specific glycosidases, in human cancer cell lines. ..
  8. Gómez L, Molinar Toribio E, Calvo Torras M, Adelantado C, Juan M, Planas J, et al. D-Fagomine lowers postprandial blood glucose and modulates bacterial adhesion. Br J Nutr. 2012;107:1739-46 pubmed publisher
  9. Thonhofer M, Gonzalez Santana A, Fischer R, Torvisco Gomez A, Saf R, Schalli M, et al. 5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease. Carbohydr Res. 2016;420:6-12 pubmed publisher
    ..This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease. ..

More Information

Publications62

  1. Van Gaal L, Maislos M, Schernthaner G, Rybka J, Segal P. Miglitol combined with metformin improves glycaemic control in type 2 diabetes. Diabetes Obes Metab. 2001;3:326-31 pubmed
    ..Miglitol can safely and effectively be added to diet and metformin in patients whose type 2 diabetes is insufficiently controlled, and improves glycaemic control by significantly reducing HbA1c and postprandial blood glucose levels. ..
  2. Drent M, Tollefsen A, van Heusden F, Hoenderdos E, Jonker J, van der Veen E. Dose-dependent efficacy of miglitol, an alpha-glucosidase inhibitor, in type 2 diabetic patients on diet alone: results of a 24-week double-blind placebo-controlled study. Diabetes Nutr Metab. 2002;15:152-9 pubmed
    ..Gastrointestinal side effects also showed dose-dependency. Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d. ..
  3. Amézqueta S, Galán E, Fuguet E, Carrascal M, Abian J, Torres J. Determination of D-fagomine in buckwheat and mulberry by cation exchange HPLC/ESI-Q-MS. Anal Bioanal Chem. 2012;402:1953-60 pubmed publisher
    ..The new method provides a means for convenient and accurate determination of D-fagomine in plant samples and foodstuffs...
  4. Blanco O, Pato C, Ruiz M, Ojea V. Synthesis of pyrrolidine homoazasugars and 3,4-dihydroxy-5-hydroxymethylprolines using aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-D-erythroses. Org Biomol Chem. 2009;7:2310-21 pubmed publisher
  5. Kato A, Miyauchi S, Kato N, Nash R, Yoshimura Y, Nakagome I, et al. Docking and SAR studies of D- and L-isofagomine isomers as human ?-glucocerebrosidase inhibitors. Bioorg Med Chem. 2011;19:3558-68 pubmed publisher
    ..These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease. ..
  6. Amézqueta S, Galán E, Vila Fernández I, Pumarola S, Carrascal M, Abian J, et al. The presence of D-fagomine in the human diet from buckwheat-based foodstuffs. Food Chem. 2013;136:1316-21 pubmed publisher
    ..A diet rich in buckwheat products would provide a daily amount of D-fagomine that may in part explain the beneficial properties traditionally attributed to buckwheat consumption. ..
  7. Takahata H. [Synthetic medicinal chemistry of the biomolecular components mimics]. Yakugaku Zasshi. 2013;133:575-85 pubmed
    ..Among them, the inhibitory activity towards intestinal sucrase of ?-1-C-L-butylarabinoiminofuranose was quite strong towards intestinal sucrase compared to the above commercial drugs. ..
  8. Han W, Liu L, Zhang X, Ye W, Pan Y, Yao X. [Chemical constituents from leaves of Morus multicaulis]. Zhongguo Zhong Yao Za Zhi. 2007;32:695-8 pubmed
    ..All compounds were isolated from this plant for the first time. ..
  9. Asano N, Nishida M, Kato A, Kizu H, Matsui K, Shimada Y, et al. Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases. J Med Chem. 1998;41:2565-71 pubmed
    ..These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I. ..
  10. Ouchi H, Mihara Y, Takahata H. A new route to diverse 1-azasugars from N-Boc-5-hydroxy-3-piperidene as a common building block. J Org Chem. 2005;70:5207-14 pubmed
    ..In addition, the synthesis of all four stereoisomers of 3,4,5-trihydroxypiperidines (18-21) classified as 1-azasugar-type glycosidase inhibitors was stereoselectively achieved from the (chiral) piperidene 3. ..
  11. Uno Y, Minatoguchi S, Arai M, Wang N, Chen X, Hashimoto K, et al. The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog. Clin Exp Pharmacol Physiol. 2005;32:805-10 pubmed
    ..Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow. ..
  12. Yokoyama H, Kannno S, Ishimura I, Node K. Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus. Metabolism. 2007;56:1458-63 pubmed
    ..Future studies are needed to elucidate the long-term effect. ..
  13. Alcaide B, Almendros P, Cabrero G, Ruiz M. Stereocontrolled access to orthogonally protected anti,anti-4-aminopiperidine-3,5-diols through chemoselective reduction of enantiopure beta-lactam cyanohydrins. J Org Chem. 2007;72:7980-91 pubmed
    ..Specifically, the utility of this novel reaction sequence has been demonstrated by the synthesis of fully orthogonally protected sialidase inhibitors. ..
  14. Bollen M, Vandebroeck A, Stalmans W. 1-Deoxynojirimycin and related compounds inhibit glycogenolysis in the liver without affecting the concentration of phosphorylase a. Biochem Pharmacol. 1988;37:905-9 pubmed
    ..Thus, the antiglycogenolytic action of these compounds is not mediated by an altered activation state of the rate-limiting enzymes of glycogenolysis and of glycogen synthesis. ..
  15. Wrodnigg T, Diness F, Gruber C, Hausler H, Lundt I, Rupitz K, et al. Probing the aglycon binding site of a beta-glucosidase: a collection of C-1-modified 2,5-dideoxy-2,5-imino-D-mannitol derivatives and their structure-activity relationships as competitive inhibitors. Bioorg Med Chem. 2004;12:3485-95 pubmed
    ..Ki values are compared with those of previously prepared close relatives. Findings suggest dramatic effects exerted by the aglycon binding site on substrate/inhibitor binding. ..
  16. Sakaguchi K, Kasuga M. [Adverse effects of alpha-glucosidase inhibitors]. Nihon Rinsho. 2007;65 Suppl 8:183-7 pubmed
  17. Brooks D. Getting into the fold. Nat Chem Biol. 2007;3:84-5 pubmed
  18. Campbell L, Baker D, Campbell R. Miglitol: assessment of its role in the treatment of patients with diabetes mellitus. Ann Pharmacother. 2000;34:1291-301 pubmed
    ..No published studies comparing miglitol with acarbose have been published, but there appears to be no major clinical or financial advantages to using one agent over the other. ..
  19. Kornhaber G, Tropak M, Maegawa G, Tuske S, Coales S, Mahuran D, et al. Isofagomine induced stabilization of glucocerebrosidase. Chembiochem. 2008;9:2643-9 pubmed publisher
    ..H/D-Ex data indicate that the binding of IFG not only restricts the local protein dynamics of the active site, but also propagates this effect into surrounding regions. ..
  20. Witte M, Kallemeijn W, Aten J, Li K, Strijland A, Donker Koopman W, et al. Ultrasensitive in situ visualization of active glucocerebrosidase molecules. Nat Chem Biol. 2010;6:907-13 pubmed publisher
    ..In addition, we illustrate the use of the fluorescent probes to study inhibitors and tentative chaperones in living cells...
  21. Martin O, Compain P, Kizu H, Asano N. Revised structure of a homonojirimycin isomer from Aglaonema treubii: first example of a naturally occurring alpha-homoallonojirimycin. Bioorg Med Chem Lett. 1999;9:3171-4 pubmed
    ..Its activity as a glycosidase inhibitor is compared to that of other homonojirimycin isomers. ..
  22. Corkran H, Munneke S, Dangerfield E, Stocker B, Timmer M. Applications and limitations of the I2-mediated carbamate annulation for the synthesis of piperidines: five- versus six-membered ring formation. J Org Chem. 2013;78:9791-802 pubmed publisher
    ..A mechanistic explanation for the formation of each annulation product could be provided, which has improved our understanding of the scope and limitations of the carbamate annulation for piperidine synthesis. ..
  23. Zhu X, Sheth K, Li S, Chang H, Fan J. Rational design and synthesis of highly potent beta-glucocerebrosidase inhibitors. Angew Chem Int Ed Engl. 2005;44:7450-3 pubmed
  24. Scheen A. Is there a role for alpha-glucosidase inhibitors in the prevention of type 2 diabetes mellitus?. Drugs. 2003;63:933-51 pubmed
    ..However, the best dosage of acarbose for this specific indication remains to be specified, especially when all three important parameters, efficacy, tolerance and cost, are taken into consideration. ..
  25. Thonhofer M, Weber P, Santana A, Fischer R, Pabst B, Paschke E, et al. Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase. Bioorg Med Chem Lett. 2016;26:1438-42 pubmed publisher
    ..New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis. ..
  26. Zechel D, Boraston A, Gloster T, Boraston C, Macdonald J, Tilbrook D, et al. Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases. J Am Chem Soc. 2003;125:14313-23 pubmed
    ..1 A resolution, reveal that additional ordering of bound solvent may present an entropic penalty to 1-deoxynojirimycin binding that does not penalize isofagomine. ..
  27. Sun Y, Ran H, Liou B, Quinn B, Zamzow M, Zhang W, et al. Isofagomine in vivo effects in a neuronopathic Gaucher disease mouse. PLoS ONE. 2011;6:e19037 pubmed publisher
    ..However, this was not correlated with a reduction in the accumulation of lipid substrates. ..
  28. Chiou W, Ma C, Chung S, Wu T, Jeong H. Similarity in the linear and non-linear oral absorption of drugs between human and rat. Int J Clin Pharmacol Ther. 2000;38:532-9 pubmed
    ..The above findings may be valuable in drug development. ..
  29. Liu B. [Study on chemical constituents of Peganum multisectum]. Zhong Yao Cai. 2011;34:1719-21 pubmed
    ..To study the chemical consituents of Peganum multisectum...
  30. Kumar K, Rathee J, Subramanian M, Chattopadhyay S. Divergent synthesis of 4-epi-fagomine, 3,4-dihydroxypipecolic acid, and a dihydroxyindolizidine and their ?-galactosidase inhibitory and immunomodulatory activities. J Org Chem. 2013;78:7406-13 pubmed publisher
    ..The bicyclic compound dihydroxyindolizidine (21) reduced the proinflammatory cytokine (IL-1? and TNF-?) levels in the LPS-activated Raw 264.7 cells without showing any enzyme-inhibition activity. ..
  31. Wang N, Minatoguchi S, Chen X, Uno Y, Arai M, Lu C, et al. Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart. Br J Pharmacol. 2004;142:983-90 pubmed
    ..4 These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein. ..
  32. de Luis Román D, del Pozo García E, Aller R, Romero Bobillo E, Conde Valentín R. [Usefulness of miglitol in patients with diabetes mellitus type 2 and insufficient control of the blood glucose]. Rev Clin Esp. 2004;204:32-4 pubmed
    ..Miglitol is a useful drug in order to improve the glycemic control in diabetic type 2 patients treated previously with other drugs and with insufficient control of the blood glucose. Its side effects are limited and transitory. ..
  33. Yu Z, Sawkar A, Whalen L, Wong C, Kelly J. Isofagomine- and 2,5-anhydro-2,5-imino-D-glucitol-based glucocerebrosidase pharmacological chaperones for Gaucher disease intervention. J Med Chem. 2007;50:94-100 pubmed
  34. Wang R, Qiu X, Bols M, Ortega Caballero F, Qing F. Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues. J Med Chem. 2006;49:2989-97 pubmed
    ..0, while iminosugar 6 is not. Iminosugar 6 also displayed good and selective inhibition of beta-glucosidase at pH 6.8. ..
  35. Sickmann H, Schousboe A, Fosgerau K, Waagepetersen H. Compartmentation of lactate originating from glycogen and glucose in cultured astrocytes. Neurochem Res. 2005;30:1295-304 pubmed
    ..Moreover, it was found that lactate originating from glycogen is compartmentalized from that derived from glucose, which lends further support to a compartmentalized metabolism in astrocytes. ..
  36. Lindbäck E, Laursen B, Poulsen J, Kilså K, Pedersen C, Bols M. A fluorescence study of isofagomine protonation in β-glucosidase. Org Biomol Chem. 2015;13:6562-6 pubmed publisher
    ..This is a radically different binding mode than has been observed with isofagomine and other iminosugars in the literature. ..
  37. Liang P, Cheng W, Lee Y, Yu H, Wu Y, Lin Y, et al. Novel five-membered iminocyclitol derivatives as selective and potent glycosidase inhibitors: new structures for antivirals and osteoarthritis. Chembiochem. 2006;7:165-73 pubmed
    ..6 nM), a new target for the development of osteoarthritis therapeutics. ..
  38. Glawar A, Best D, Ayers B, Miyauchi S, Nakagawa S, Aguilar Moncayo M, et al. Scalable syntheses of both enantiomers of DNJNAc and DGJNAc from glucuronolactone: the effect of N-alkylation on hexosaminidase inhibition. Chemistry. 2012;18:9341-59 pubmed publisher
  39. van den Berg R, Donker Koopman W, van Boom J, Aerts H, Noort D. Design and synthesis of 2-acetamidomethyl derivatives of isofagomine as potential inhibitors of human lysosomal beta-hexosaminidases. Bioorg Med Chem. 2004;12:891-902 pubmed
    ..The 1-N-imino-2 acetamidomethyl derivative 5 proved to be a rather selective inhibitor with a K(i) of 2.4 microM for homogenate of human spleen lysosomal beta-hexosaminidase...
  40. Kang Y, Terrier P, Ding C, Douglas D. Solution and gas-phase H/D exchange of protein-small-molecule complexes: Cex and its inhibitors. J Am Soc Mass Spectrom. 2012;23:57-67 pubmed publisher
    ..1 ms. The gas-phase H/Dx measurements show that at least some complexes retain different conformations from the Cex ions on a time scale of seconds. ..
  41. Jabgunde A, Kalamkar N, Chavan S, Sabharwal S, Dhavale D. Synthesis of new six- and seven-membered 1-N-iminosugars as promising glycosidase inhibitors. Bioorg Med Chem. 2011;19:5912-5 pubmed publisher
    ..The hydrochloride salts of 4a/4b and 5b were found to be specific ?-galactosidase and moderate ?-glucosidae inhibitors, respectively, in micro molar range. ..
  42. Mark B, Vocadlo D, Zhao D, Knapp S, Withers S, James M. Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor. J Biol Chem. 2001;276:42131-7 pubmed publisher
    ..This interaction appears to contribute to the unexpected potency of GalNAc-isofagomine toward SpHEX...
  43. Chai Y, Wang J, Liu M, Yi H, Sun L, You X, et al. Design, synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-aminomethylpiperidin-1-yl)fluoroquinolone derivatives. Bioorg Med Chem Lett. 2011;21:3377-80 pubmed publisher
    ..125-4 ?g/mL). In addition, compounds 16 and 17 (MICs: 4 ?g/mL) were 2- to 8-fold more potent than the reference drugs against Pseudomonas aeruginosa. ..
  44. Berteau O, Sandstrom C, Bielicki J, Anson D, Kenne L. Glycosidase-substrate interactions analysis by STD-NMR spectroscopy: study of alpha-L-fucosidase. J Am Chem Soc. 2003;125:15296-7 pubmed
    ..These findings will be useful for the design of new inhibitors and to optimize the synthetic properties (transglycosylation) of alpha-l-fucosidases. ..
  45. Scott L, Spencer C. Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus. Drugs. 2000;59:521-49 pubmed
    ..Miglitol may prove particularly beneficial in elderly patients and those with hepatic impairment or mild to moderate renal impairment, in whom other oral antidiabetic agents are contraindicated or need to be used with caution. ..
  46. Sedová P, Buffa R, Kettou S, Huerta Angeles G, Hermannová M, Leierová V, et al. Preparation of hyaluronan polyaldehyde-a precursor of biopolymer conjugates. Carbohydr Res. 2013;371:8-15 pubmed publisher
    ..The function of polyaldehyde as precursor for other modification was illustrated in the reaction with lysine. ..
  47. Markad S, Karanjule N, Sharma T, Sabharwal S, Dhavale D. Synthesis and evaluation of glycosidase inhibitory activity of N-butyl 1-deoxy-D-gluco-homonojirimycin and N-butyl 1-deoxy-L-ido-homonojirimycin. Bioorg Med Chem. 2006;14:5535-9 pubmed
  48. Wrodnigg T, Stütz A, Tarling C, Withers S. Fine tuning of beta-glucosidase inhibitory activity in the 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) system. Carbohydr Res. 2006;341:1717-22 pubmed
    ..Thus, a set of compounds was assembled with Ki values between 2 nM and 1 microM against Agrobacterium sp. beta-glucosidase. ..
  49. Shen J, Edwards N, Hong Y, Murray G. Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase. Biochem Biophys Res Commun. 2008;369:1071-5 pubmed publisher
    ..Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease. ..
  50. Serra Vinardell J, Diaz L, Gutiérrez de Terán H, Sánchez Ollé G, Bujons J, Michelakakis H, et al. Selective chaperone effect of aminocyclitol derivatives on G202R and other mutant glucocerebrosidases causing Gaucher disease. Int J Biochem Cell Biol. 2014;54:245-54 pubmed publisher
    ..In conclusion, we have tested novel compounds that have shown some chaperone effect on particular glucocerebrosidase mutant enzymes, supporting the enhancement therapy as an alternative approach for Gaucher disease. ..
  51. Rigat B, Mahuran D. Diltiazem, a L-type Ca(2+) channel blocker, also acts as a pharmacological chaperone in Gaucher patient cells. Mol Genet Metab. 2009;96:225-32 pubmed publisher
    ..However, at neutral pH, found in the endoplasmic reticulum, Diltiazem exhibited both of these properties. Thus Diltiazem exhibits the biochemical characteristics of a glucocerebrosidase pharmacological chaperone. ..
  52. Blériot Y, Gretzke D, Krülle T, Butters T, Dwek R, Nash R, et al. Looking glass inhibitors: efficient synthesis and biological evaluation of D-deoxyfuconojirimycin. Carbohydr Res. 2005;340:2713-8 pubmed
    ..1,6-Dideoxygalactostatin, the mirror image of 1-deoxy-L-fuconojirimycin, was efficiently prepared from 2,3-O-isopropylidene-L-lyxonolactone in four steps and evaluated as a glycosidase inhibitor. ..
  53. Morera S, Vigouroux A, Stubbs K. A potential fortuitous binding of inhibitors of an inverting family GH9 ?-glycosidase derived from isofagomine. Org Biomol Chem. 2011;9:5945-7 pubmed publisher
    ..In contrast to what was observed in the first report using these compounds with inverting glycosidases from family GH6, these inhibitors do not adopt a distorted conformation in the active site. ..