Discovery of a 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) inhibitor of c-Met kinase for the treatment of cancer.
J Med Chem
; 54(12): 4092-108, 2011 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-21608528
ABSTRACT
c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Benzocicloeptenos
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Receptores Proteína Tirosina Quinases
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Antineoplásicos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article