Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands.
Eur J Med Chem
; 86: 700-9, 2014 Oct 30.
Article
em En
| MEDLINE
| ID: mdl-25232966
ABSTRACT
Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Receptor MT1 de Melatonina
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Receptor MT2 de Melatonina
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article