Abstract
3-(Hetero)aryl substituted 7-azaindoles possessing multikinase inhibitor activity are readily accessed in a one-pot Masuda borylation-Suzuki coupling sequence. Several promising derivatives were identified as apoptosis inducers and, emphasizing the multikinase inhibition potential, as sphingosine kinase 2 inhibitors. Our measurements provide additional insights into the structure-activity relationship of meriolin derivatives, suggesting derivatives bearing a pyridine moiety with amino groups in 2-position as most active anticancer compounds and thus as highly promising candidates for future in vivo studies.
Keywords:
Apoptosis; Masuda borylation-Suzuki coupling; Meriolin; One-pot reaction; Sphingosine kinase 2; Synthetic methods.
Copyright © 2019 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 / 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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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
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Bridged Bicyclo Compounds, Heterocyclic / chemistry
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Jurkat Cells
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Molecular Structure
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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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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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Bridged Bicyclo Compounds, Heterocyclic
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Protein Kinase Inhibitors
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Pyrimidines
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meriolin 3
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase 2, human