Abstract
A new series of pyrazolo[3,4-d]pyrimidine-3,6-diamines was designed and synthesized as potent and selective inhibitors of the nonreceptor tyrosine kinase, ACK1. These compounds arose from efforts to rigidify an earlier series of N-aryl pyrimidine-5-carboxamides. The synthesis and structure-activity relationships of this new series of inhibitors are reported. The most promising compounds were also profiled for their pharmacokinetic properties.
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods
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Crystallography, X-Ray / methods
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Diamines / antagonists & inhibitors*
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Inhibitory Concentration 50
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Male
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Models, Chemical
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Molecular Conformation
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / chemistry
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Pyrazoles / chemistry*
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Pyrimidines / chemistry*
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
Substances
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Diamines
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Enzyme Inhibitors
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Pyrazoles
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Pyrimidines
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Protein-Tyrosine Kinases
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TNK2 protein, human