Abstract
The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.
MeSH terms
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Crystallography, X-Ray
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Drug Design
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Humans
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Receptor, TIE-2 / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry
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Thiazoles / pharmacology*
Substances
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Protein Kinase Inhibitors
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Pyrimidines
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Thiazoles
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thienopyrimidine
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Receptor, TIE-2