Abstract
A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure-activity relationship studies indicated that electron-withdrawing groups (X=CF3, R(1)=F, R(2)=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.
Keywords:
1,2,3-Triazole; Antiproliferative activity; Pyrrolo[2,3-b]pyridine derivatives; Synthesis; c-Met.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Drug Design
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Drug Screening Assays, Antitumor
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Humans
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Models, Molecular
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Molecular Docking Simulation
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Neoplasms / drug therapy
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Neoplasms / metabolism
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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 / metabolism
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Pyridines / chemistry*
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Pyridines / pharmacology*
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Pyrroles / chemistry*
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Pyrroles / pharmacology*
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Structure-Activity Relationship
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Triazoles / chemistry*
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Triazoles / pharmacology*
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyridines
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Pyrroles
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Triazoles
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Proto-Oncogene Proteins c-met
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pyrrolo(2, 3-b)pyridine