Synthesis and glycosidase inhibitory profiles of functionalised morpholines and oxazepanes

Burland, P. A., Osborn, H. M. I. ORCID: https://orcid.org/0000-0002-0683-0457 and Turkson, A. (2011) Synthesis and glycosidase inhibitory profiles of functionalised morpholines and oxazepanes. Bioorganic & Medicinal Chemistry, 19 (18). pp. 5679-5692. ISSN 0968-0896 doi: 10.1016/j.bmc.2011.07.019

Abstract/Summary

In this work libraries of morpholines and oxazepanes have been prepared via the reductive amination reaction between dialdehydes, derived from carbohydrates, and a range of amines. In this way, functionalised morpholines and oxazepanes have been prepared that include N-alkylated derivatives, disaccharide analogues, and ester containing derivatives. The abilities of these functionalised morpholines and oxazepanes to inhibit a broad panel of glycosidase enzymes, that are associated with a range of diseases, have been probed and in this way new inhibitors of a range of glycosidases, but particularly β-d-galactosidase derived from Bovine kidney, have been discovered. N-Alkyl morpholines demonstrated the best inhibition profiles for this enzyme and derivatives (15a)–(15d) acted as non-competitive inhibitors with IC50 values of 55.1–88.6 μM. Within this study, some preliminary structure–activity relationships are proposed, and it is demonstrated that N-substituted morpholines display better inhibitory profiles for the enzymes analysed than any of the N-substituted oxazepanes.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/22033
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Medicinal Chemistry Research Group
Publisher	Elsevier
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