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Bioorg Med Chem Lett ; 24(21): 5093-7, 2014 11 01.
Article in English | MEDLINE | ID: mdl-25282552

ABSTRACT

We report a series of phenyl substituted pyridazin-3-ones substituted with morpholino-pyrimidines. The SAR of the phenyl was explored and their c-Met kinase and cell-based inhibitory activity toward c-Met driven cell lines were evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent morpholino-pyridazinone scaffold, with particular focus on the phenyl and pyrimidine substituents.


Subject(s)
Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Pyridazines/chemistry , Binding Sites , Cell Line , Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Humans , Molecular Docking Simulation , Protein Binding , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Protein Structure, Tertiary , Proto-Oncogene Proteins c-met/metabolism , Pyridazines/chemical synthesis , Pyridazines/pharmacology , Structure-Activity Relationship
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