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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026560,
umls-concept:C0036751,
umls-concept:C0220781,
umls-concept:C0243072,
umls-concept:C0268563,
umls-concept:C1554184,
umls-concept:C1659436,
umls-concept:C1707689,
umls-concept:C1883254
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pubmed:issue |
8
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pubmed:dateCreated |
2008-4-15
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pubmed:abstractText |
Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key step. Structure-activity relationships established that serotonin and noradrenaline reuptake inhibition are functions of stereochemistry and aryl/aryloxy ring substitution. Consequently, selective SRI, selective NRI and dual SNRIs were all identified. One of these compounds, a potent and selective dual SNRI, (SS)-5a was selected as a candidate for further pre-clinical evaluation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:DeurChristopherC,
pubmed-author:FishPaul VPV,
pubmed-author:GanXinminX,
pubmed-author:GreeneKeriK,
pubmed-author:HoopleDavidD,
pubmed-author:MackennyMalcolmM,
pubmed-author:ParaKimberly SKS,
pubmed-author:ReevesKeithK,
pubmed-author:RyckmansThomasT,
pubmed-author:StiffCoryC,
pubmed-author:StobieAlanA,
pubmed-author:WakenhutFlorianF,
pubmed-author:WhitlockGavin AGA
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
2562-6
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pubmed:meshHeading |
pubmed-meshheading:18387300-Cells, Cultured,
pubmed-meshheading:18387300-Drug Design,
pubmed-meshheading:18387300-Humans,
pubmed-meshheading:18387300-Liver,
pubmed-meshheading:18387300-Molecular Structure,
pubmed-meshheading:18387300-Morpholines,
pubmed-meshheading:18387300-Norepinephrine,
pubmed-meshheading:18387300-Serotonin,
pubmed-meshheading:18387300-Serotonin Uptake Inhibitors,
pubmed-meshheading:18387300-Stereoisomerism,
pubmed-meshheading:18387300-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition.
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pubmed:affiliation |
Department of Genitourinary Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. paul.fish@pfizer.com
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pubmed:publicationType |
Journal Article
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