Design and synthesis of 4,5,6,7-tetrahydro-1H-1,2-diazepin-7-one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors.
Bioorg Med Chem Lett
; 27(1): 24-29, 2017 01 01.
Article
em En
| MEDLINE
| ID: mdl-27890378
ABSTRACT
Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azepinas
/
Desenho de Fármacos
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
/
Inibidores da Fosfodiesterase 4
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2017
Tipo de documento:
Article