Abstract
A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC(50)s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors.
MeSH terms
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Autoimmune Diseases / drug therapy
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Benzimidazoles / antagonists & inhibitors*
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
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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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Pyrimidines / antagonists & inhibitors*
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Pyrimidines / chemistry
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Solubility
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Structure-Activity Relationship
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src-Family Kinases / metabolism
Substances
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Benzimidazoles
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Pyrimidines
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Protein-Tyrosine Kinases
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases
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pyrimidine