81117-35-3

Usage

Uses

Used in Pharmaceutical Industry:
N-(n-Nonyl)deoxynojirimycin is used as an inhibitor of a-glucosidase 1 for the treatment of Gaucher disease. Gaucher disease is a lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in various organs. N-Nonyl-DNJ can help reduce the substrate of the enzyme, thereby alleviating the symptoms of the disease.
Used in Antiviral Applications:
N-(n-Nonyl)deoxynojirimycin is used as an inhibitor of HIV cytopathicity, which is the ability of the virus to cause damage to host cells. By inhibiting this process, N-Nonyl-DNJ can potentially reduce the severity of HIV infection and slow down the progression of the disease.

Biological Activity

Glucosidase inhibitor (IC 50 values are 0.42 and 8.4 μ M for acid α -glucosidase and α -1,6-glucosidase respectively). Inhibits liver glycogen breakdown in vivo . Also acts as a chemical chaperone; chaperones β -Glu folding at neutral p.H. allowing the stabilized enzyme to transit from the endoplasmic reticulum to the golgi, enabling proper trafficking to the lysosome.

Biochem/physiol Actions

NN-DNJ is a glucosidase inhibitor that acts as a pharmacologic chaperone. NN-DNJ also acts synergistically with proteostasis modulators such as celastrol and MG132 to stabilize mutant proteins in properly folded states. NN-DNJ stabilizes various proteins against misfolding, increasing proper trafficking from the endoplasmic reticulum. There is potential use in studying diseases marked by misfolded proteins and has shown antiviral activity.

InChI:InChI=1/C15H31NO4/c1-2-3-4-5-6-7-8-9-16-10-13(18)15(20)14(19)12(16)11-17/h12-15,17-20H,2-11H2,1H3

Upstream product

• 143-08-8 nonyl alcohol 
• 4282-42-2 1-iodononane 
• 146747-37-7 (2S,3S,4S,5R)-2-(hydroxymethyl)piperidine-3,4,5-triol 
• 693-58-3 1-Bromononane 
• 126663-71-6 1,5-dideoxy-1,5-imino-L-galactitol 
• 143406-74-0 (2R,3S,4R,5R)-3,4,5-trihydroxy-2-hydroxymethyl piperidine 
• 752952-68-4 (2R,3S,4S,5R)-2-(hydroxymethyl)piperidine-3,4,5-triol 
• 76738-52-8 (2S,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)piperidine 
• 14233-48-8 2,3,4,6-tetra-O-benzyl-D-glucitol 
• 16647-80-6 (2S,3R,4R,5S)-2-hydroxymethyl-3,4,5-piperidinetriol 
• 14199-63-4 1-deoxymannojirimycin 

Relevant academic research and scientific papers

Microwave-assisted process for preparing N-nonyldeoxynojirimycin

The present invention relates to a method of manufacturing N-nonyl deoxynojirimycin having an excellent inhibitory activity against andalpha;-glucoside. To be specifically, the present invention relates to the method of manufacturing N-nonyl deoxynojirimycin using microwave which is manufactured by conducting a substitution reaction of deoxynojirimycin, which is a starting material, into 1-bromononane in the presence of K_2CO_3 base, diluting the same with a dimethyl formamide (DMF) solvent and conducting a heating reaction of the same by microwave.COPYRIGHT KIPO 2019

Exploring the effect of chirality on the therapeutic potential of N-alkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease

In the frame of a research program aimed to explore the relationship between chirality of iminosugars and their therapeutic potential, herein we report the synthesis of N-akyl L-deoxyiminosugars and the evaluation of the anti-inflammatory properties of selected candidates for the treatment of Pseudomonas aeruginosa infections in Cystic Fibrosis (CF)lung disease. Target glycomimetics were prepared by the shortest and most convenient approach reported to date, relying on the use of the well-known PS-TPP/I2 reagent system to prepare reactive alkoxyalkyl iodides, acting as key intermediates. Iminosugars ent-1-3 demonstrated to efficiently reduce the inflammatory response induced by P. aeruginosa in CuFi cells, either alone or in synergistic combination with their D-enantiomers, by selectively inhibiting NLGase. Surprisingly, the evaluation in murine models of lung disease showed that the amount of ent-1 required to reduce the recruitment of neutrophils was 40-fold lower than that of the corresponding D-enantiomer. The remarkably low dosage of the L-iminosugar, combined with its inability to act as inhibitor for most glycosidases, is expected to limit the onset of undesired effects, which are typically associated with the administration of its D-counterpart. Biological results herein obtained place ent-1 and congeners among the earliest examples of L-iminosugars acting as anti-inflammatory agents for therapeutic applications in Cystic Fibrosis.

A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase

Human nonlysosomal glucosylceramidase (GBA2) is one of several enzymes that controls levels of glycolipids and whose activity is linked to several human disease states. There is a major need to design or discover selective GBA2 inhibitors both as chemical tools and as potential therapeutic agents. Here, we describe the development of a fluorescence polarization activity-based protein profiling (FluoPol-ABPP) assay for the rapid identification, from a 350+ library of iminosugars, of GBA2 inhibitors. A focused library is generated based on leads from the FluoPol-ABPP screen and assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP on cell extracts containing recombinant, overexpressed glycosidase as the easily accessible enzyme source.

Structure–Activity Studies of N-Butyl-1-deoxynojirimycin (NB-DNJ) Analogues: Discovery of Potent and Selective Aminocyclopentitol Inhibitors of GBA1 and GBA2

Analogues of N-butyl-1-deoxynojirimycin (NB-DNJ) were prepared and assayed for inhibition of ceramide-specific glucosyltransferase (CGT), non-lysosomal β-glucosidase 2 (GBA2) and the lysosomal β-glucosidase 1 (GBA1). Compounds 5 a–6 f, which carry sterically demanding nitrogen substituents, and compound 13, devoid of the C3 and C5 hydroxy groups present in DNJ/NB-DGJ (N-butyldeoxygalactojirimycin) showed no inhibitory activity for CGT or GBA2. Inversion of stereochemistry at C4 of N-(n-butyl)- and N-(n-nonyl)-DGJ (compounds 24) also led to a loss of activity in these assays. The aminocyclopentitols N-(n-butyl)- (35 a), N-(n-nonyl)-4-amino-5-(hydroxymethyl)cyclopentane- (35 b), and N-(1-(pentyloxy)methyl)adamantan-1-yl)-1,2,3-triol (35 f), were found to be selective inhibitors of GBA1 and GBA2 that did not inhibit CGT (>1 mm), with the exception of 35 f, which inhibited CGT with an IC50 value of 1 mm. The N-butyl analogue 35 a was 100-fold selective for inhibiting GBA1 over GBA2 (Ki values of 32 nm and 3.3 μm for GBA1 and GBA2, respectively). The N-nonyl analogue 35 b displayed a Ki value of ?14 nm for GBA1 inhibition and a Ki of 43 nm for GBA2. The N-(1-(pentyloxy)methyl)adamantan-1-yl) derivative 35 f had Ki values of ≈16 and 14 nm for GBA1 and GBA2, respectively. The related N-bis-substituted aminocyclopentitols were found to be significantly less potent inhibitors than their mono-substituted analogues. The aminocyclopentitol scaffold should hold promise for further inhibitor development.

Pharmaceutically active piperidine derivatives

Compounds of formula (I): wherein R represents various substituent groups, are useful as inhibitors of glucosylceramide synthase.

IMINOSUGARS AND METHODS OF TREATING ARENAVIRAL INFECTIONS

Provided are methods of treating a disease or condition caused by or associated with a virus belonging to the Arenaviridae family using iminosugars, such as DNJ derivatives.

Identification of potent and selective glucosylceramide synthase inhibitors from a library of N-alkylated iminosugars

Glucosylceramide synthase (GCS) is an important target for clinical drug development for the treatment of lysosomal storage disorders and a promising target for combating type 2 diabetes. Iminosugars are useful leads for the development of GCS inhibitors; however, the effective iminosugar type GCS inhibitors reported have some unwanted cross-reactivity toward other glyco-processing enzymes. In particular, iminosugar type GCS inhibitors often also inhibit to some extent human acid glucosylceramidase (GBA1) and the nonlysosomal glucosylceramidase (GBA2), the two enzymes known to process glucosylceramide. Of these, GBA1 itself is a potential drug target for the treatment of the lysosomal storage disorder, Gaucher disease, and selective GBA1 inhibitors are sought after as potential chemical chaperones. The physiological importance of GBA2 in glucosylceramide processing in relation to disease states is less clear, and here, selective inhibitors can be of use as chemical knockout entities. In this communication, we report our identification of a highly potent and selective N-alkylated l-ido-configured iminosugar. In particular, the selectivity of 27 for GCS over GBA1 is striking.

METHODS OF TREATING POXVIRAL INFECTIONS

Provided are methods of treating a disease or condition caused by or associated with a virus belonging to the Poxviridae family using iminosugars, such as DNJ derivatives.

IMINOSUGARS AND METHODS OF TREATING FILOVIRAL DISEASES

Provided are methods of treating a disease or condition caused by or associated with a virus belonging to the Filoviridae family using iminosugars, such as DNJ derivatives.

METHODS OF TREATING ORTHOMYXOVIRAL INFECTIONS

Provided are novel iminosugars and methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Orthomyxoviridae family using iminosugars, such as DNJ derivatives.