- The discovery of benzanilides as c-Met receptor tyrosine kinase inhibitors by a directed screening approach.
The discovery of benzanilides as c-Met receptor tyrosine kinase inhibitors by a directed screening approach.
Bioorganic & medicinal chemistry letters (2011-08-13)
Joanne V Allen, Catherine Bardelle, Kevin Blades, Dave Buttar, Louise Chapman, Nicola Colclough, Alexander G Dossetter, Andrew P Garner, Alan Girdwood, Christine Lambert, Andrew G Leach, Brian Law, John Major, Helen Plant, Anthony M Slater
PMID21835616
摘要
A directed screen of a relatively small number of compounds, selected for kinase ATP pocket binding potential, yielded a novel series of hit compounds (1). Hit explosion on two binding residues identified compounds 27 and 43 as the best leads for an optimization program having reduced secondary metabolism, as measured by in vitro rat hepatocytes incubation, leading to oral bio-availability. Structure-activity relationships and molecular modeling have suggested a binding mode for the most potent inhibitor 12.
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