Linked Life Data

10725312

Source:http://linkedlifedata.com/resource/pubmed/id/10725312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-5-1
pubmed:abstractText
Previously we have proposed and provided evidence for a metabolic scheme leading to 3-carbamoyl-2-phenylpropionaldehyde from the antiepileptic drug felbamate. This aldehyde was found to undergo reversible cyclization to form the more stable cyclic carbamate 4-hydroxy-5-phenyl-tetrahydro-1,3-oxazin-2-one or undergo elimination to form 2-phenylpropenal. The cyclic carbamate bears structural similarity to 4-hydroxycyclophosphamide and there is an intriguing parallelism between the pathway from the cyclic carbamate to 2-phenylpropenal and the known pathway from 4-hydroxycyclophosphamide to acrolein. The similarity of these transformations led us to consider 5-phenyl-1,3-oxazinane-2,4-dione, which could arise from an oxidation of the cyclic carbamate, as a potential metabolite of felbamate. As the formation of this dione species may have both potential pharmacologic and toxicologic implications for felbamate therapy, we wished to study its reactivity. We have developed a synthesis of 5-phenyl-1, 3-oxazinane-2,4-dione and evaluated its reactivity in vitro. This dione was found to undergo base-catalyzed decomposition to three products, one of which is the major human metabolite of felbamate, 3-carbamoyl-2-phenylpropionic acid. Furthermore, we have found evidence for the presence of the dione in human urine after felbamate treatment through the identification of its major in vitro decomposition product, 2-phenylacrylamide 11.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
434-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
The synthesis, in vitro reactivity, and evidence for formation in humans of 5-phenyl-1,3-oxazinane-2,4-dione, a metabolite of felbamate.
pubmed:affiliation
Chemistry Department, University of Virginia, Charlottesville, Virginia 22901, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't