Novel 3-methylindoline inhibitors of EZH2: Design, synthesis and SAR.
Bioorg Med Chem Lett
; 27(2): 217-222, 2017 01 15.
Article
em En
| MEDLINE
| ID: mdl-27923618
ABSTRACT
EZH2 (enhancer of zeste homologue 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that catalyzes the methylation of lysine 27 of histone H3 (H3K27). Dysregulation of EZH2 activity is associated with several human cancers and therefore EZH2 inhibition has emerged as a promising therapeutic target. Several small molecule EZH2 inhibitors with different chemotypes have been reported in the literature, many of which use a bicyclic heteroaryl core. Herein, we report the design and synthesis of EZH2 inhibitors containing an indoline core. Partial saturation of an indole to an indoline provided lead compounds with nanomolar activity against EZH2, while also improving solubility and oxidative metabolic stability.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores Enzimáticos
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Proteína Potenciadora do Homólogo 2 de Zeste
/
Indóis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia