5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease

Martin Thonhofer; Andres Gonzalez Santana; Roland Fischer; Ana Torvisco Gomez; Robert Saf; Michael Schalli; Arnold Stütz; Stephen G. Withers

doi:10.1016/j.carres.2015.10.009

5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease

Martin Thonhofer, Andres Gonzalez Santana, Roland Fischer, Ana Torvisco Gomez, Robert Saf, Michael Schalli, Arnold Stütz, Stephen G. Withers

Research output: Contribution to journal › Article › peer-review

Abstract

Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-d-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.

Original language	English
Pages (from-to)	6-12
Journal	Carbohydrate Research
Volume	420
DOIs	https://doi.org/10.1016/j.carres.2015.10.009
Publication status	Published - Dec 2015

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10.1016/j.carres.2015.10.009

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Thonhofer, M., Gonzalez Santana, A., Fischer, R., Torvisco Gomez, A., Saf, R., Schalli, M., Stütz, A., & Withers, S. G. (2015). 5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease. Carbohydrate Research, 420, 6-12. https://doi.org/10.1016/j.carres.2015.10.009

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title = "5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease",

abstract = "Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-d-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.",

author = "Martin Thonhofer and {Gonzalez Santana}, Andres and Roland Fischer and {Torvisco Gomez}, Ana and Robert Saf and Michael Schalli and Arnold St{\"u}tz and Withers, {Stephen G.}",

year = "2015",

month = dec,

doi = "10.1016/j.carres.2015.10.009",

language = "English",

volume = "420",

pages = "6--12",

journal = "Carbohydrate Research",

issn = "0008-6215",

publisher = "Elsevier Ltd.",

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T1 - 5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease

AU - Thonhofer, Martin

AU - Gonzalez Santana, Andres

AU - Fischer, Roland

AU - Torvisco Gomez, Ana

AU - Saf, Robert

AU - Schalli, Michael

AU - Stütz, Arnold

AU - Withers, Stephen G.

PY - 2015/12

Y1 - 2015/12

N2 - Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-d-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.

AB - Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-d-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.

U2 - 10.1016/j.carres.2015.10.009

DO - 10.1016/j.carres.2015.10.009

M3 - Article

SN - 0008-6215

VL - 420

SP - 6

EP - 12

JO - Carbohydrate Research

JF - Carbohydrate Research

ER -

5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease

Abstract

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