Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors.
Bioorg Med Chem
; 26(3): 637-646, 2018 02 01.
Article
em En
| MEDLINE
| ID: mdl-29305298
ABSTRACT
A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Inibidores de Proteínas Quinases
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Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article