Abstract
New fused bicyclic lactam head groups as rigidified analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Depending on the functionalities and the size of these bicyclic head groups, potent inhibitors of RON tyrosine kinase with various level of selectivity against c-Met tyrosine kinase were obtained.
Keywords:
Bicyclic head group; Homology model; Molecular docking; RON; RTK inhibitors; c-Met.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor / drug effects
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Chemistry Techniques, Synthetic
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Drug Design
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Drug Evaluation, Preclinical / methods
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Heterocyclic Compounds, 2-Ring / chemistry*
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Humans
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Inhibitory Concentration 50
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Lactams / chemistry
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Molecular Docking Simulation
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Molecular Targeted Therapy
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins c-met / antagonists & inhibitors*
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Proto-Oncogene Proteins c-met / chemistry
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Pyrazoles / chemistry*
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Receptor Protein-Tyrosine Kinases / chemistry
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Receptor Protein-Tyrosine Kinases / metabolism
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Stomach Neoplasms / drug therapy
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Stomach Neoplasms / pathology
Substances
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Antineoplastic Agents
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Heterocyclic Compounds, 2-Ring
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LCRF-0004
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Lactams
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Protein Kinase Inhibitors
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Pyrazoles
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Proto-Oncogene Proteins c-met
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RON protein
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Receptor Protein-Tyrosine Kinases