186759-56-8Relevant articles and documents
Anin vitro-in vivosequential cascade for the synthesis of iminosugars from aldoses
Kuska, Justyna,O'Reilly, Elaine,Ryan, James,Taday, Freya,Yeow, Kathryn
, p. 4327 - 4331 (2021/07/12)
Here, we report a chemoenzymatic approach for the preparation of a small panel of biologically important iminosugars from readily available aldoses. Our approach involves anin vitrotransaminase-mediated amination of aldoses in combination with anin vivose
METHODS OF TREATING POMPE DISEASE
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Paragraph 0061-0062; 0067-0068, (2021/04/10)
Disclosed herein are novel uses of ADMDP stereoisomers or their derivatives for the manufacture of a medicament for treating Pompe disease. Accordingly, the present disclosure provides a method of treating Pompe disease in a subject. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, an ester or a solvate thereof, wherein R1 and R2 are independently H or alkyl optionally substituted by -NH2 or -OH, so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the Pompe disease. According to certain embodiments of the present disclosure, the compound of formula (I) may serve a stabilizer of α-glucosidase via preventing its denaturalization of deactivation.
A common strategy towards the synthesis of 1,4-dideoxy-1,4-imino-L-xylitol, deacetyl (+)-anisomycin and amino-substituted piperidine iminosugars
Harit, Vimal Kant,Ramesh, Namakkal G.
, (2020/05/08)
A strategy towards the synthesis of three different target molecules, namely 1,4-dideoxy-1,4-imino-L-xylitol, deacetyl (+)-anisomycin and amino-substituted piperidine iminosugars, molecules of potential biological and medicinal significance, is reported from a common amino-vicinal diol intermediate derived from tri-O-benzyl-D-glucal. Construction of the key pyrrolidine ring present in 1,4-dideoxy-1,4-imino-L-xylitol and (+)-anisomycin was a consequence of thermodynamically driven concomitant intramolecular nucleophilic addition reaction of the amino group to the resultant aldehyde obtained by oxidative cleavage of the amino-vicinal diol. Alternatively, double nucleophilic substitution on an amino-diol, after mesylation, with various amines delivered amino-substituted piperidine iminosugars in good yields.
TREATMENT OF FABRY DISEASE
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Paragraph 0130; 0131; 0132; 0133, (2018/04/11)
Disclosed herein are novel uses of a polyhydroxylated pyrrolidine for the manufacture of a medicament for treating Fabry disease (FD). Accordingly, the present disclosure provides a method of treating a subject having or suspected of having FD. The method
Structural essentials for β-: N -acetylhexosaminidase inhibition by amides of prolines, pipecolic and azetidine carboxylic acids
Glawar,Martínez,Ayers,Hollas,Ngo,Nakagawa,Kato,Butters,Fleet,Jenkinson
, p. 10371 - 10385 (2016/11/18)
This paper explores the computer modelling aided design and synthesis of β-N-acetylhexosaminidase inhibitors along with their applicability to human disease treatment through biological evaluation in both an enzymatic and cellular setting. We investigated the importance of individual stereocenters, variations in structure-activity relationships along with factors influencing cell penetration. To achieve these goals we modified nitrogen heterocycles in terms of ring size, side chains present and ring nitrogen derivatization. By reducing the inhibitor interactions with the active site down to the essentials we were able to determine that besides the established 2S,3R trans-relationship, the presence and stereochemistry of the CH2OH side chain is of crucial importance for activity. In terms of cellular penetration, N-butyl side chains favour cellar uptake, while hydroxy- and carboxy-group bearing sidechains on the ring nitrogen retarded cellular penetration. Furthermore we show an early proof of principle study that β-N-acetylhexosaminidase inhibitors can be applicable to use in a potential anti-invasive anti-cancer strategy.
Synthesis of hydroxylated pyrrolidines by allenic cyclisation
Ng, Pearly Shuyi,Bates, Roderick W.
, p. 6356 - 6362 (2016/09/23)
The diastereoselective gold(I) catalysed cyclisation of highly substituted aminoallene derivatives allows the synthesis of both epi-DAB-1 and di-epi-lentiginosine. While the sense of stereoselectivity observed is in line with earlier observations on analo
Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency
Cheng, Wei-Chieh,Wang, Jen-Hon,Li, Huang-Yi,Lu, Sheng-Jhih,Hu, Jia-Ming,Yun, Wen-Yi,Chiu, Cheng-Hsin,Yang, Wen-Bin,Chien, Yin-Hsiu,Hwu, Wuh-Liang
, p. 14 - 20 (2016/08/01)
A unique molecular library consisting of all sixteen synthetic ADMDP (1-aminodeoxy-DMDP) stereoisomers has been prepared and evaluated for inhibitory activity against α-Gal A, and ability to impart thermal stabilization of this enzyme. The results of this
Synthesis and anti-tuberculosis activity of glycitylamines
Corkran, Hilary M.,Dangerfield, Emma M.,Haslett, Gregory W.,Stocker, Bridget L.,Timmer, Mattie S.M.
, p. 693 - 702 (2016/02/09)
A series of glycitylamines, which were prepared in few steps from readily available carbohydrates, were tested for their ability to inhibit tuberculosis growth in an Alamar Blue BCG colourimetric assay. Several derivatives, including (2R,3R)-1-(hexadecyla
Azasugar inhibitors as pharmacological chaperones for Krabbe disease
Hill, Chris H.,Viuff, Agnete H.,Spratley, Samantha J.,Salamone, Stéphane,Christensen, Stig H.,Read, Randy J.,Moriarty, Nigel W.,Jensen, Henrik H.,Deane, Janet E.
, p. 3075 - 3086 (2015/09/08)
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure-activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.
Synthesis of pyrrolidine iminosugars, (-)-lentiginosine, (-)-swainsonine and their 8a-epimers from d-glycals
Ansari, Alafia A.,Vankar
, p. 12555 - 12567 (2014/03/21)
Synthesis of pyrrolidine iminosugars has been described from d-glycals via dihydroxylation, oxidative cleavage and double nucleophilic displacement as the key steps. The pyrrolidines obtained have been utilized for the synthesis of important bicyclic iminosugars, viz. (-)-lentiginosine and (-)-swainsonine and their 8a-epimers, which are known to be glycosidase inhibitors.
