Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity: part 2.
Eur J Med Chem
; 44(11): 4702-15, 2009 Nov.
Article
en En
| MEDLINE
| ID: mdl-19665823
ABSTRACT
Derivatives of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine were synthesized. These compounds contain the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy or 2-methyl derivative. In vitro binding tests were performed to determine the affinity of the compounds for the 5-HT(1A) receptor and serotonin transporter (SERT) proteins in the rat brain cortex. In vivo studies, particularly the inducible hypothermia test and forced swimming test, were conducted to determine agonistic/antagonistic activity with pre- and postsynaptic 5-HT(1A) receptors. Molecular modeling techniques were used to determine the binding modes of the selected compounds at the 5-HT(1A) receptor and SERT. The SAR analysis showed that the presence of the 3-(4-piperidyl)-1H-indole group or its 5-methoxy derivative, as well as a para substitution with -OCH(3) or -F in the aryl ring of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine, results in an increased affinity for both the 5-HT(1A) receptors and SERT. In contrast, the presence of the 2-methyl-3-(4-piperidyl)-1H-indole group resulted in a considerable decrease in binding affinity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
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Inhibidores Selectivos de la Recaptación de Serotonina
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Receptor de Serotonina 5-HT1A
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Proteínas de Transporte de Serotonina en la Membrana Plasmática
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Antidepresivos
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
FR
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FRANCE
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FRANCIA
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FRANÇA