Medicinal use of Iminosugars

Cox, Timothy M.; Platt, Frances M.; Aerts, Johannes M. F. G.

doi:10.1002/9780470517437.ch13

Cited by 11 publications

(9 citation statements)

References 70 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Iminosugars, widespread in plants and microorganisms, are carbohydrate mimetics in which the endocyclic oxygen is replaced by nitrogen. 4 These kinds of compounds raise many synthetic challenges, and as inhibitors or chaperones of carbohydrate-processing enzymes, 5 they open the way to treat a wide range of diseases including diabetes, 6 viral infections, 7 tumor metastasis, 8 and lysosomal storage disorders. 9 However, the use of iminosugar derivatives as immunosuppressive agents is an area that is less explored.…”

Section: B S Supporting Informationmentioning

confidence: 99%

Synthetic N-Alkylated Iminosugars as New Potential Immunosuppressive Agents

Wang

Xiong

Jia

et al. 2011

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

The new emerging immunosuppressive effects displayed by iminosugars have not been much investigated so far. Several new N-alkyl dideoxy iminoalditols were designed and synthesized to explore their immunosuppressive effects. These iminosugars inhibited the proliferation of mouse splenocytes and the secretion of both IFN-γ and IL-4, which are the hallmark cytokines of Th1 and Th2 cells, respectively. Some compounds exerted good inhibitory effects. More importantly, the synthetic iminosugars prolonged the allograft survival in the mouse skin transplantation experiment. Our results provide a lead for further elucidation of the structure-activity relationships and modifications of iminosugars for better immunosuppressive agents.

show abstract

Section: B S Supporting Informationmentioning

confidence: 99%

Synthetic N-Alkylated Iminosugars as New Potential Immunosuppressive Agents

Wang

Xiong

Jia

et al. 2011

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

show abstract

“…Over the last few decades, interesting broad-spectrum therapeutic applications have been found that have led to the development of three iminosugar drugs ( Figure 1 ), namely Glyset ( N -hydroxyethyl-deoxynojirimycin, Miglitol, 1 ), which is used for the therapeutic treatment of type 2 diabetes [ 6 ], Zavesca ( N -butyldeoxynojirimycin, NBDNJ, 2 ), which is used for lysosomal storage disorders including Gaucher and Niemann–Pick type C diseases [ 7 , 8 , 9 ], and Galafold (deoxygalactonojirimycin, DGJ, 3 ), which was recently approved for the treatment of Fabry disease [ 10 , 11 ]. A variety of other iminosugars have also been identified as therapeutic candidates against malignancies [ 12 ], viral infections [ 13 , 14 ] and other genetic disorders, including cystic fibrosis [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars

et al. 2020

View full text Add to dashboard Cite

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a–b and 11a–b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I2/ImH activating system, which provided the desired compounds in high yields (94–96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a–b and 11a–b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.

show abstract

“…Compounds that inhibit GCS have been of pharmacologic interest for many years due to their potential utility in lowering glycosphingolipid (GSL) levels. Elevated GSL levels have been implicated in numerous disorders, including Type II Diabetes, Gaucher, Sandhoff, Tay–Sachs, Niemann–Pick C, and Fabry diseases, and therefore GCS inhibitors have been investigated as treatments for enzyme deficiencies. − Iminosugars have been under increased investigation due to their potential utility for these conditions, and both Zavesca and Miglitol are currently marketed therapies which make use of such a core . The potent GCS inhibitor 7 was first reported by Aerts et al in 1998, where it was reported to be 100-fold better in inhibiting GCS than n -butyldeoxynojirimycin .…”

Section: Introductionmentioning

confidence: 99%

“…The potent GCS inhibitor 7 was first reported by Aerts et al in 1998, where it was reported to be 100-fold better in inhibiting GCS than n -butyldeoxynojirimycin . Since its discovery, 7 has been shown to have potential applications in Gaucher’s Disease, Type II Diabetes, Niemann–Pick C, ulcerative colitis, and cystic fibrosis …”

Section: Introductionmentioning

confidence: 99%

“…1À7 Iminosugars have been under increased investigation due to their potential utility for these conditions, and both Zavesca and Miglitol are currently marketed therapies which make use of such a core. 8 The potent GCS inhibitor 7 was first reported by Aerts et al in 1998, where it was reported to be 100-fold better in inhibiting GCS than n-butyldeoxynojirimycin. 9 Since its discovery, 7 has been shown to have potential applications in Gaucher's Disease, Type II Diabetes, NiemannÀPick C, ulcerative colitis, and cystic fibrosis.…”

Section: ' Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Process Development of a Potent Glucosylceramide Synthase Inhibitor

Cooper¹,

Lee²,

Silva³

et al. 2011

Org. Process Res. Dev.

View full text Add to dashboard Cite

An economic, scalable process for the production of glucosylceramide synthase (GCS) inhibitor 7 has been developed. Herein we report a three-step synthesis to aldehyde 4 with high yield and purity that employs the selective cleavage of an endocyclic CÀO bond of a THP ether using borane/THF as the key step. This particular methodology has not been used previously from a development standpoint and offers an attractive way towards introducing pentanol side chains. Aldehyde 4 is then coupled with deoxynojirimycin via flow hydrogenation using an H-Cube to safely produce the free base of 7, which is isolated as an MSA salt in 50% overall yield. Herein we discuss the evolution of this process from its original form and the thermodynamics of its associated chemistry.

show abstract

Medicinal use of Iminosugars

Cited by 11 publications

References 70 publications

Synthetic N-Alkylated Iminosugars as New Potential Immunosuppressive Agents

Synthetic N-Alkylated Iminosugars as New Potential Immunosuppressive Agents

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars

Process Development of a Potent Glucosylceramide Synthase Inhibitor

Contact Info

Product

Resources

About