Abstract
A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based on a tri-substituted triazine scaffold has led to the discovery of potent and selective inhibitors of mTOR.
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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Cell Line, Tumor
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Humans
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Morpholines / chemical synthesis
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Morpholines / chemistry*
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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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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Protein Kinases / chemistry*
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Protein Kinases / metabolism
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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
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TOR Serine-Threonine Kinases
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Triazines / chemical synthesis
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Triazines / chemistry*
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Triazines / pharmacology
Substances
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Antineoplastic Agents
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Pyrimidines
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Triazines
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Protein Kinases
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MTOR protein, human
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TOR Serine-Threonine Kinases