Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of G_M1-gangliosidosis-related human lysosomal β-galactosidase

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• 作者：Martin Thonhofer^a ; Patrick Weber^a ; Andres Gonzalez Santana^b ; Roland Fischer^c ; Bettina M. Pabst^d ; Eduard Paschke^d ; Michael Schalli^a ; Arnold E. Stü ; tz^a ; ^{stuetz@tugraz.at" class="auth_mail" title="E-mail the corresponding author} ; Marion Tschernutter^d ; Werner Windischhofer^d ; Stephen G. Withers^b
• 关键词：Iminoalditol ; 4-epi-Isofagomine ; Galactosidase inhibitor ; Pharmacological chaperone ; GM1-gangliosidosis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：26
• 期：5
• 页码：1438-1442
• 全文大小：887 K

文摘

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 G_M1-gangliosidosis.