Abstract
This Letter describes the medicinal chemistry effort towards a series of novel imidazo[1,5-a]pyrazine derived inhibitors of ACK1. Virtual screening led to the discovery of the initial hit, and subsequent exploration of structure-activity relationships and optimization of drug metabolism and pharmacokinetic properties led to the identification of potent, selective and orally bioavailable ACK1 inhibitors.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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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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Mice
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Protein Kinase Inhibitors / chemical synthesis
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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-Tyrosine 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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Structure-Activity Relationship
Substances
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Imidazoles
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Protein Kinase Inhibitors
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Pyrazines
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Protein-Tyrosine Kinases
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TNK2 protein, human