Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease.
Eur J Med Chem
; 103: 289-301, 2015 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-26363507
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine4 receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo[1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Transtornos Cognitivos
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Receptores 5-HT4 de Serotonina
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Agonismo Parcial de Drogas
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Doença de Alzheimer
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article