Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1.
J Med Chem
; 61(10): 4635-4640, 2018 05 24.
Article
em En
| MEDLINE
| ID: mdl-29718668
ABSTRACT
We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S)-3 readily attains free plasma concentrations above PDE1 IC50 values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue. These compounds represent promising new tools to probe the value of PDE1 inhibition in the treatment of cardiovascular disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
Quinazolinas
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 1
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Descoberta de Drogas
/
Miocárdio
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article