Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

Martin Thonhofer; Patrick Weber; Andres Gonzalez Santana; Roland Fischer; Bettina M. Pabst; Eduard Paschke; Michael Schalli; Arnold Stütz; Marion Tschernutter; Werner Windischhofer; Stephen G. Withers

doi:10.1016/j.bmcl.2016.01.059

Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

Martin Thonhofer, Patrick Weber, Andres Gonzalez Santana, Roland Fischer, Bettina M. Pabst, Eduard Paschke, Michael Schalli, Arnold Stütz^*, Marion Tschernutter, Werner Windischhofer, Stephen G. Withers

^*Corresponding author for this work

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

Abstract

From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis.

Original language	English
Pages (from-to)	1438-1442
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2016.01.059
Publication status	Published - 2016

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10.1016/j.bmcl.2016.01.059

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Thonhofer, M., Weber, P., Santana, A. G., Fischer, R., Pabst, B. M., Paschke, E., Schalli, M., Stütz, A., Tschernutter, M., Windischhofer, W., & Withers, S. G. (2016). Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase. Bioorganic & Medicinal Chemistry Letters, 26(5), 1438-1442. https://doi.org/10.1016/j.bmcl.2016.01.059

Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase. / Thonhofer, Martin; Weber, Patrick; Santana, Andres Gonzalez et al.
In: Bioorganic & Medicinal Chemistry Letters, Vol. 26, No. 5, 2016, p. 1438-1442.

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

Thonhofer, M, Weber, P, Santana, AG, Fischer, R, Pabst, BM, Paschke, E, Schalli, M, Stütz, A, Tschernutter, M, Windischhofer, W & Withers, SG 2016, 'Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.', Bioorganic & Medicinal Chemistry Letters, vol. 26, no. 5, pp. 1438-1442. https://doi.org/10.1016/j.bmcl.2016.01.059

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abstract = "From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis.",

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author = "Martin Thonhofer and Patrick Weber and Santana, {Andres Gonzalez} and Roland Fischer and Pabst, {Bettina M.} and Eduard Paschke and Michael Schalli and Arnold St{\"u}tz and Marion Tschernutter and Werner Windischhofer and Withers, {Stephen G.}",

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AU - Thonhofer, Martin

AU - Weber, Patrick

AU - Santana, Andres Gonzalez

AU - Fischer, Roland

AU - Pabst, Bettina M.

AU - Paschke, Eduard

AU - Schalli, Michael

AU - Stütz, Arnold

AU - Tschernutter, Marion

AU - Windischhofer, Werner

AU - Withers, Stephen G.

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AB - From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis.

KW - imino alditol prepn isofagomine GM1 gangliosidosis galactosidase inhibitor human

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DO - 10.1016/j.bmcl.2016.01.059

M3 - Article

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SP - 1438

EP - 1442

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 5

ER -

Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

Abstract

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