Abstract
Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines. These compounds are lead-like, with low molecular weight, good physical properties and oral bioavailability.
MeSH terms
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Administration, Oral
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Biological Availability
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Chemistry, Pharmaceutical / methods
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Drug Design
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Humans
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Imidazoles / administration & dosage
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Imidazoles / chemical synthesis*
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Inhibitory Concentration 50
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Models, Chemical
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Molecular Conformation
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Neovascularization, Pathologic
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacology*
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Pyrimidines / administration & dosage
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology*
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Receptor, TIE-2 / antagonists & inhibitors*
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Receptor, TIE-2 / chemistry
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Structure-Activity Relationship
Substances
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Imidazoles
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Protein Kinase Inhibitors
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Pyrimidines
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Receptor, TIE-2
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pyrimidine