209787-64-4

Upstream product

• 87-72-9 D-lyxose 
• 77-76-9 2,2-dimethoxy-propane 
• 84588-33-0 benzyl α-D-lyxopyranoside 
• 100-51-6 benzyl alcohol 
• 1114-34-7 D-lyxose 

Downstream Products

• 275363-98-9 4-epi-isofagomine 
• 104292-65-1 benzyl 3,4-anhydro-β-L-ribopyranoside 
• 1032939-20-0 1-O-benzyl-2,3-O-isopropylidene-α-D-lyxopyranoside-4-O-dibenzylphosphate 
• 74491-81-9 benzyl 2,3-O-isopropylidene-β-L-erythro-pentopyranosid-4-ulose 

Relevant academic research and scientific papers

(5aR)-5a-C-Pentyl-4-epi-isofagomine: A powerful inhibitor of lysosomal β-galactosidase and a remarkable chaperone for mutations associated with GM1-gangliosidosis and Morquio disease type B

This report is about the identification, synthesis and initial biological characterization of derivatives of 4-epi-isofagomine as pharmacological chaperones (PC) for human lysosomal β-galactosidase. The two epimers of 4-epi-isofagomine carrying a pentyl group at C-5a, namely (5aR)- and (5aS)-5a-C-pentyl-4-epi-isofagomine, were prepared by an innovative procedure involving in the key step the addition of nitrohexane to a keto-pentopyranoside. Both epimers were evaluated as inhibitors of the human β-galactosidase: the (5aR)-stereoisomer (compound 1) was found to be a very potent inhibitor of the enzyme (IC50?=?8?nM, 30× more potent than 4-epi-isofagomine at pH 7.3) with a high selectivity for this glycosidase whereas the (5aS) epimer was a much weaker inhibitor. In addition, compound 1 showed a remarkable activity as a PC. It significantly enhanced the residual activity of mutant β-galactosidase in 15 patient cell lines out of 23, with enhancement factors greater than 3.5 in 10 cell lines and activity restoration up to 91% of normal. Altogether, these results indicated that (5aR)-5a-C-pentyl-4-epi-isofagomine constitutes a promising PC-based drug candidate for the treatment of GM1-gangliosidosis and Morquio disease type B.

4-EPI-ISOFAGOMINE DERIVATIVES

The present invention relates to 4-epi-isofagomine derivatives, pharmaceutically acceptable salts thereof, and the use of said 4-epi-isofagomine derivatives in the treatment and/or prevention of lysosomal storage diseases. The present invention is further