Abstract
A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50=0.008 microM), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Aurora Kinases
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Polyploidy
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology*
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Pyrroles / chemical synthesis*
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Pyrroles / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Pyrimidines
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Pyrroles
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Aurora Kinases
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Protein Serine-Threonine Kinases