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These compounds were designed as simplified 4\u2010epi\u2010isofagomine (4\u2010epi\u2010IFG) mimics and were expected to behave as selective inhibitors of \u03b2\u2010galactosidases. All compounds were indeed found to be highly selective for \u03b2\u2010galactosidases versus \u03b1\u2010glycosidases, as they generally did not inhibit coffee bean \u03b1\u2010galactosidase or other \u03b1\u2010glycosidases. Some compounds were also found to be inhibitors of almond \u03b2\u2010glucosidase. The <jats:italic>N<\/jats:italic>\u2010alkyl DIR derivatives were only modest inhibitors of bovine \u03b2\u2010galactosidase, with IC<jats:sub>50<\/jats:sub> values in the 30\u2013700\u2005\u03bc<jats:sc>m<\/jats:sc> range. Likewise, imino\u2010<jats:sc>l<\/jats:sc>\u2010ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced \u03b2\u2010galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the \u2018pseudo\u2010anomeric\u2019 configuration in this series does not appear to play a role. Human lysosomal \u03b2\u2010galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC<jats:sub>50<\/jats:sub> values in the 100\u2005\u03bc<jats:sc>m<\/jats:sc> range), while 4\u2010epi\u2010IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1\u2010gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7\u2010fold.<\/jats:p>","DOI":"10.1002\/cmdc.201500485","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T03:10:58Z","timestamp":1449630658000},"page":"133-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["<i>N<\/i>\u2010Alkyl\u2010, 1\u2010<i>C<\/i>\u2010Alkyl\u2010, and 5\u2010<i>C<\/i>\u2010Alkyl\u20101,5\u2010dideoxy\u20101,5\u2010imino\u2010(<scp>l<\/scp>)\u2010ribitols as Galactosidase Inhibitors"],"prefix":"10.1002","volume":"11","author":[{"given":"Sophie","family":"Front","sequence":"first","affiliation":[{"name":"Institut de Chimie Organique et Analytique (ICOA) UMR 7311 Universit\u00e9 d'Orl\u00e9ans Centre National de la Recherche Scientifique (CNRS)  Rue de Chartres 45067 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