title: 4-thiophenoxy-N-(3,4,5-trialkoxyphenyl)pyrimidine-2-amines as potent and selective inhibitors of the T-cell tyrosine kinase p56lck.
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.
authors.affiliation: Celltech R&D, 216 Bath Road, Slough, SL1 4EN, UK. dave.moffat@celltechgroup.com
authors.forename: D F C
authors.initials: DF
authors.lastname: Moffat
authors.forename: R A
authors.initials: RA
authors.lastname: Allen
authors.forename: S E
authors.initials: SE
authors.lastname: Rapecki
authors.forename: P D
authors.initials: PD
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: O'Connell
authors.forename: M C
authors.initials: MC
authors.lastname: Hutchings
authors.forename: M A
authors.initials: MA
authors.lastname: King
authors.forename: B A
authors.initials: BA
authors.lastname: Boyce
authors.forename: M J
authors.initials: MJ
authors.lastname: Perry
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000588:Amines; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)