Abstract
A series of 2'-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC(50)=0.027 microM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC(50)=0.11 microM) and as such, serves as a lead candidate for further optimization studies.
MeSH terms
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Anilides / chemical synthesis*
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Anilides / chemistry
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Anilides / pharmacology*
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Cell Line
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Cell Proliferation / drug effects
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Drug Evaluation, Preclinical
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Humans
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Inhibitory Concentration 50
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Macrophages / drug effects
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Molecular Structure
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Piperidines / chemistry*
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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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Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Anilides
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Anti-Inflammatory Agents
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Piperidines
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Protein Kinase Inhibitors
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Receptor, Macrophage Colony-Stimulating Factor