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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2011-4-25
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pubmed:abstractText |
The synthesis and structure-activity relationship (SAR) of a novel series of aryl piperazine napthyridinone D(2) partial agonists is described. Our goal was to optimize the affinities for the D(2), 5-HT(2A) and 5-HT(1A) receptors, such that the D(2)/5-HT(2A) ratio was greater than 5 to ensure maximal occupancy of these receptors when the D(2) occupancy reached efficacious levels. This strategy led to identification of PF-00217830 (2) with robust inhibition of sLMA (MED=0.3mg/kg) and DOI-induced head twitches in rats (31% and 78% at 0.3 and 1mg/kg) with no catalepsy observed at the highest dose tested (10 mg/kg).
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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 |
May
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AkunneHyacinth CHC,
pubmed-author:ChoiChungC,
pubmed-author:FavorDavid ADA,
pubmed-author:FayLorraine KLK,
pubmed-author:FitzgeraldLawrenceL,
pubmed-author:JohnsonDouglas SDS,
pubmed-author:NichollsKimK,
pubmed-author:RepineJoseph TJT,
pubmed-author:SerpaKevin AKA,
pubmed-author:SnyderBradley JBJ,
pubmed-author:WhetzelSteven ZSZ,
pubmed-author:WhiteAndrew DAD,
pubmed-author:ZhangLimingL
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2621-5
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pubmed:meshHeading |
pubmed-meshheading:21353774-Animals,
pubmed-meshheading:21353774-Antipsychotic Agents,
pubmed-meshheading:21353774-Bipolar Disorder,
pubmed-meshheading:21353774-Drug Discovery,
pubmed-meshheading:21353774-Haplorhini,
pubmed-meshheading:21353774-Male,
pubmed-meshheading:21353774-Molecular Structure,
pubmed-meshheading:21353774-Naphthyridines,
pubmed-meshheading:21353774-Piperazines,
pubmed-meshheading:21353774-Rats,
pubmed-meshheading:21353774-Receptors, Dopamine D2,
pubmed-meshheading:21353774-Schizophrenia,
pubmed-meshheading:21353774-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Discovery of PF-00217830: aryl piperazine napthyridinones as D2 partial agonists for schizophrenia and bipolar disorder.
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pubmed:affiliation |
Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA. doug.johnson@pfizer.com
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pubmed:publicationType |
Journal Article
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