4-thiophenoxy-N-(3,4,5-trialkoxyphenyl)pyrimidine-2-amines as potent and selective inhibitors of the T-cell tyrosine kinase p56lck.
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.
Moffat
D F C
DF
Celltech R&D, 216 Bath Road, Slough, SL1 4EN, UK. dave.moffat@celltechgroup.com
Allen
R A
RA
Rapecki
S E
SE
Davis
P D
PD
O'Connell
J
J
Hutchings
M C
MC
King
M A
MA
Boyce
B A
BA
Perry
M J
MJ
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
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)