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1. 4-thiophenoxy-N-(3,4,5-trialkoxyphenyl)pyrimidine-2-amines as potent and selective inhibitors of the T-cell tyrosine kinase p56lck.

Author

Moffat DF, Allen RA, Rapecki SE, Davis PD, O'Connell J, Hutchings MC, King MA, Boyce BA, and Perry MJ

Subjects
Adjuvants, Immunologic chemistry, Amines chemistry, Binding, Competitive, Cells, Cultured, Enzyme Inhibitors chemistry, Humans, Interleukin-2 immunology, Models, Molecular, Molecular Structure, Pyrimidines chemistry, Structure-Activity Relationship, T-Lymphocytes enzymology, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha immunology, Adjuvants, Immunologic pharmacology, Amines pharmacology, Enzyme Inhibitors pharmacology, Lymphocyte Specific Protein Tyrosine Kinase p56(lck) antagonists & inhibitors, Pyrimidines pharmacology, T-Lymphocytes drug effects
Abstract

We have developed a series of 4-thiophenoxy-N-(3,4,5-trialkoxyphenyl) pyrimidine-2-amines as potent and selective inhibitors of p56lck tyrosine kinase activity. In particular, the most potent inhibitor shows cellular activity in T-cell receptor (TCR) stimulated models of cytokine release, which suggests an immunomodulatory role for this class of inhibitor.

Published
2004
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