Abstract
We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Aurora Kinases
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Biological Availability
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Cell Line, Tumor
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Female
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Humans
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Imidazoles / chemistry
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Pyrazines / chemistry
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Pyrazines / pharmacokinetics
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Pyrazines / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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Imidazoles
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Protein Kinase Inhibitors
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Pyrazines
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imidazo(1,2-a)pyrazine
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Aurora Kinases
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Protein Serine-Threonine Kinases