In:
European Journal of Organic Chemistry, Wiley, Vol. 2010, No. 7 ( 2010-03), p. 1258-1283
Abstract:
The structure–activity relationship of lipophilic aza‐C‐glycosides as inhibitors of the three enzymes of glucosylceramide metabolism is investigated. A library of β‐aza‐C‐glycosides was synthesized with variations in N ‐alkylation and the linker length/type to the lipophilic moiety. A cross‐metathesis reaction was used to prepare a second library of α‐aza‐C‐glycosides with D ‐ gluco , L ‐ ido and D ‐ xylo iminosugar cores possessing analogous linker variations. Evaluation of both libraries did not reveal a potent or selective inhibitor of glucosylceramide synthase. However, β‐aza‐C‐glycoside 43 was found to be a selective inhibitor of β‐glucosidase 2. The α‐aza‐C‐glycosides – especially with a D ‐ xylo core (e.g. 80 ) – proved to be very potent and selective inhibitors of glucocerebrosidase.
Type of Medium:
Online Resource
ISSN:
1434-193X
,
1099-0690
DOI:
10.1002/ejoc.v2010:7
DOI:
10.1002/ejoc.200901208
Language:
English
Publisher:
Wiley
Publication Date:
2010
detail.hit.zdb_id:
1475010-7
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