Synthesis and biological evaluation of N-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)benzenesulfonamide derivatives as new BET bromodomain inhibitors for anti-hematologic malignancies activities.
Mol Divers
; 21(1): 125-136, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-27858214
ABSTRACT
The bromodomain and extra-terminal proteins (BETs), in particular BRD4, has been reported to play important roles in cancer, inflammation, obesity, cardiovascular disease, and neurological disorders. In this paper, a series of benzomorpholinone derivatives were synthesized and biologically evaluated as BETs inhibitors. Detailed structure-activity relationship studies led to the discovery of several new potent compounds, of which 15h and 15i displayed [Formula see text] values of 2.8 and 4.5 [Formula see text] against BRD4 (D1), respectively, and showed good anti-proliferation activities against four hematologic malignancies cell lines at low-micromolar concentrations, including MV4-11, OCI-LY10, Pfeifer, and Su-DHL-6 cells. This chemotype could be further optimized with respect to its potency and drug-like properties in the future.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Neoplasias Hematológicas
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Mol Divers
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China