Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs.
Bioorg Med Chem Lett
; 15(24): 5567-73, 2005 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-16219465
ABSTRACT
Novel 5-HT(1) autoreceptor ligands based on the N-4-aryl-piperazinyl-N'-ethyl-5,6,7,8-tetrahydropyrido[4', 3'4,5]thieno[2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT(1A) and 5-HT(1B) receptors. Strategies for the development of dual 5-HT(1A) and 5-HT(1B) antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT(1A) and the 5-HT(1B) receptors and was characterized further with respect to selectivity, electrically stimulated [(3)H]5-HT release and in vivo efficacy.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Antagonistas do Receptor 5-HT1 de Serotonina
/
Antidepressivos
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article