Discovery of PF-00217830: aryl piperazine napthyridinones as D2 partial agonists for schizophrenia and bipolar disorder.
Bioorg Med Chem Lett
; 21(9): 2621-5, 2011 May 01.
Article
em En
| MEDLINE
| ID: mdl-21353774
ABSTRACT
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).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Antipsicóticos
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Receptores de Dopamina D2
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Naftiridinas
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos