New potent 5-HT(2A) receptor ligands containing an N'-cyanopicolinamidine nucleus: Synthesis and in vitro pharmacological evaluation.
Eur J Med Chem
; 47(1): 520-9, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-22133459
ABSTRACT
N'-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT(1A) receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT(2A) and moderate to no affinity for other relevant receptors (5-HT(1A), 5-HT(2C), D(1), D(2), α(1) and α(2)). N'-cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with K(i)=0.000185nM, was the most active and selective derivative for the 5-HT(2A) receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Picolínicos
/
Desenho de Fármacos
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Receptor 5-HT2A de Serotonina
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália
País de publicação:
FR
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FRANCE
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FRANCIA
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FRANÇA