10324. Isofagomine

Nomenclature

CAS number: 169105-89-9
(3R,4R,5R)-5-(Hydroxymethyl)-3,4-piperidinediol; (3R,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine.
C6H13NO3; mol wt 147.17.
C 48.97%, H 8.90%, N 9.52%, O 32.61%.

Description and references

Glycosidase inhibitior; iminosugar analog of glucose. Binds to the active site of glucocerebrosidase, the lysosomal enzyme deficient in Gaucher's disease; acts as a pharmacological chaperone to improve stability and delivery of mutant forms of the enzyme. Prepn: T. M. Jespersen et al., Angew. Chem. Int. Ed. Engl. 33, 1778 (1994) DOI; eidem, Tetrahedron 50, 13449 (1994) DOI. Improved synthesis: H. Ouchi et al., Tetrahedron Lett. 45, 7053 (2004) DOI. Glycosidase inhibition profile: W. Dong et al., Biochemistry 35, 2788 (1996) DOI PubMed. Effect on glucocerebrosidase trafficking to the lysosome: R. A. Steet et al., Proc. Natl. Acad. Sci. USA 103, 13813 (2006) DOI PubMed; J.-S. Shen et al., Biochem. Biophys. Res. Commun. 369, 1071 (2008) DOI PubMed.

Chemical structure

Properties

[α]D20 +19.6° (c = 0.85 in ethanol).

Derivative

Tartrate.

Nomenclature

CAS number: 919364-56-0
AT-2101; Plicera (Amicus).
C6H13NO3.C4H6O6; mol wt 297.26.
C 40.40%, H 6.44%, N 4.71%, O 48.44%.

Therapeutic Category

In treatment of Gaucher's disease.