Abstract
A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Drug Discovery
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Glucosyltransferases / antagonists & inhibitors*
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Glucosyltransferases / metabolism*
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Humans
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Mice
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Mice, Inbred C57BL
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Glucosyltransferases
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ceramide glucosyltransferase