Abstract
This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Aurora Kinases
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Drug Screening Assays, Antitumor
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HCT116 Cells
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Humans
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Mice
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Neoplasm Transplantation
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Neoplasms, Experimental / drug therapy*
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Neoplasms, Experimental / enzymology
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Phenylurea Compounds / chemistry*
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Phenylurea Compounds / pharmacology*
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Structure-Activity Relationship
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Thiazoles / chemistry*
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Thiazoles / pharmacology*
Substances
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Antineoplastic Agents
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Quinazolines
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SNS 314
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Thiazoles
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Aurora Kinases
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Protein Serine-Threonine Kinases