505085-66-5Relevant academic research and scientific papers
Expeditious synthesis of a common intermediate of L-1-deoxyallonojirimycin and L- 1-deoxymannoj irimycin
Ferreira, J. Franck,Botuha, Candice,Chemla, Fabrice,Perez-Luna, Alejandro
, p. 2238 - 2241 (2009)
The expeditious synthesis of a common intermediate of L- 1deoxyallonojirimycin (L-allo-DNJ) and L-1-deoxymannojirimycin (L-marano-DNJ) is reported. This intermediate is obtained in highly diastereo- and enantioselectivity with 38.4% overall yield in six s
Biological properties of D- and L-1-deoxyazasugars
Kato, Atsushi,Kato, Noriko,Kano, Erika,Adachi, Isao,Ikeda, Kyoko,Yu, Liang,Okamoto, Tadashi,Banba, Yasunori,Ouchi, Hidekazu,Takahata, Hiroki,Asano, Naoki
, p. 2036 - 2044 (2005)
L-Enantiomers of 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (manno-DNJ), 1-deoxyallonojirimycin (allo-DNJ), 1-deoxyaltronojirimycin (altro-DNJ), 1-deoxygalactonojirimycin (galacto-DNJ), 1-deoxygulonojirimycin (gulo-DNJ), and 1-deoxyidonojirimycin (ido-DNJ) were prepared according to prior methods for the D-enantiomers. These enantiospecific syntheses established unambiguously the absolute configuration of naturally occurring DNJ, manno-DNJ, allo-DNJ, altro-DNJ, and gulo-DNJ. Although D-DNJ and D-galacto-DNJ are known to be powerful competitive inhibitors of α-glucosidase and α-galactosidase, respectively, with Ki values in the nM range, L-DNJ and L-galacto-DNJ were noncompetitive inhibitors of α-glucosidase and α-galactosidase, respectively, with Ki values in the μM range. However, the azasugar mimicking the structure of the terminal sugar moiety of the natural substrate is not always an inhibitor of the glycosidase responsible for the hydrolysis. D-manno-DNJ is known as a much better inhibitor of α-L-fucosidase than α-mannosidase, while L-allo-DNJ was a better inhibitor than D-manno-DNJ of α-mannosidase. L-galacto-DNJ can be regarded as the 6-hydroxylated derivative of deoxyfuconojirimycin (DFJ), which is a powerful inhibitor of α-L-fucosidase with a Ki value in the nM range. However, this replacement of the methyl group in DFJ by a hydroxymethyl group reduced its affinity by about 50-fold. This suggests that there is a hydrophobic region in or around the active site of α-L-fucosidase. It has been found that inhibitors of human lysosomal glycosidases have therapeutic potential for the corresponding lysosomal storage diseases (Nat. Med. 1999, 5, 112; Proc. Natl. Acad. Sci. USA, 2002, 99, 15428). Inhibition of human lysosomal glycosidases by the 1-deoxyazasugars synthesized was investigated. D-galacto-DNJ is a potent inhibitor of lysosomal α-galactosidase (IC 50 = 90 nM) and is now being evaluated preclinically for its potential use in Fabry disease, while D-DNJ inhibiting α-glucosidase (IC50 = 40 nM) potently does not appear to become a potential therapeutic agent because of additional inhibitory activity toward glycoprotein processing α-glucosidases. On the other hand, although L-allo-DNJ is a moderate inhibitor of α-mannosidase (IC50 = 64 μM), it may become a key compound for the drug design of potential therapeutic agents for α-mannosidosis.
Chiral disubstituted piperidinyl ureas: A class of dual diacylglycerol lipase-α and ABHD6 inhibitors
Deng, Hui,Van Der Wel, Tom,Van Den Berg, Richard J.B.H.N.,Van Den Nieuwendijk, Adrianus M.C.H.,Janssen, Freek J.,Baggelaar, Marc P.,Overkleeft, Hermen S.,Van Der Stelt, Mario
supporting information, p. 982 - 988 (2017/07/12)
Inhibitors of diacylglycerol lipases and α,β-hydrolase domain containing protein 6 (ABHD6) are potential leads for the development of therapeutic agents for metabolic and neurodegenerative disorders. Here, we report the enantioselective synthesis and structure activity relationships of triazole ureas featuring chiral, hydroxylated 2-benzylpiperidines as dual inhibitors of DAGLα and ABHD6. The chirality of the carbon bearing the C2 substituent, as well as the position of the hydroxyl (tolerated at C5, but not at C3) has profound influence on the inhibitory activity of both DAGLα and ABHD6, as established using biochemical assays and competitive activity-based protein profiling on mouse brain extracts.
A general approach to the synthesis of 1-deoxy-L-iminosugars
Guaragna, Annalisa,D'Errico, Stefano,D'Alonzo, Daniele,Pedatella, Silvana,Palumbo, Giovanni
, p. 3473 - 3476 (2008/02/11)
A stereoselective procedure for the preparation of non-naturally occurring deoxy iminosugars belonging to L-series has been developed. The synthesis involves the construction of the key intermediate bicycle pyperidine 8, available in few steps by the coup
Diastereoselective route to piperidine and indolizidine scaffolds from enantiopure vinylsulfinyl-containing amino alcohols
Montoro, Raul,Marquez, Francesc,Llebaria, Amadeu,Delgado, Antonio
, p. 217 - 223 (2007/10/03)
A new route to functionalized piperidine and indolizidine scaffolds, based on the diastereoselective intramolecular Michael cyclization of vinylsulfinyl-containing amino alcohols 1-3, has been developed. Pyrolytic elimination of the resulting cycloadducts resulted in the regioselective formation of the corresponding tetrahydropyridines and indolizidines. The observed regiochemical course of this process can be explained mainly in terms of the steric bias imposed by the disposition of the arylsulfinyl group and the concerted syn mechanism accepted for this kind of elimination. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
