Abstract
Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Breast Neoplasms
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Female
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Gene Expression
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / physiology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Models, Molecular
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Phosphoinositide-3 Kinase Inhibitors
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Protein Binding
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Receptor, trkA / antagonists & inhibitors*
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Signal Transduction / drug effects
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Structure-Activity Relationship
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Aza Compounds
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Indoles
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Phosphoinositide-3 Kinase Inhibitors
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Vascular Endothelial Growth Factor A
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Receptor, trkA