Indole acids as a novel PDE2 inhibitor chemotype that demonstrate pro-cognitive activity in multiple species.
Bioorg Med Chem Lett
; 28(6): 1122-1126, 2018 04 01.
Article
em En
| MEDLINE
| ID: mdl-29534798
ABSTRACT
An internal HTS effort identified a novel PDE2 inhibitor series that was subsequently optimized for improved PDE2 activity and off-target selectivity. The optimized lead, compound 4, improved cognitive performance in a rodent novel object recognition task as well as a non-human primate object retrieval task. In addition, co-crystallization studies of close analog of 4 in the PDE2 active site revealed unique binding interactions influencing the high PDE isoform selectivity.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
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Ácido Acético
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 2
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Disfunção Cognitiva
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Indóis
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article