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21608528

Source:http://linkedlifedata.com/resource/pubmed/id/21608528

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pubmed-article:21608528pubmed:abstractTextc-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.lld:pubmed
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pubmed-article:21608528pubmed:articleTitleDiscovery 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.lld:pubmed
pubmed-article:21608528pubmed:affiliationDepartment of Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, BMB-2-114, Boston, Massachusetts 02115, United States. jason_katz2@merck.comlld:pubmed
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