1.
Bioorg Med Chem Lett
; 21(18): 5224-9, 2011 Sep 15.
Article
in English
| MEDLINE
| ID: mdl-21835616
ABSTRACT
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.