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

Current Medicinal Chemistry

Volumn 11, Issue 6, 2004, Pages 747-753

  Moffat, Dave F C ^a,b   Allen, R A ^a   Rapecki, S E ^a   Davis, P D ^a   O'Connell, J ^a   Hutchings, M C ^a   King, M A ^a   Boyce, B A ^a   Perry, M J ^a  

^a UCB PHARMA   (Belgium)

^b Celltech R and D ^*  (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 THIOPHENOXY N (3,4,5 TRIALKOXYPHENYL)PYRIMIDINE 2 AMINE DERIVATIVE; ADENOSINE TRIPHOSPHATE; BENZENE DERIVATIVE; CALCINEURIN; CYCLOSPORIN A; CYTOKINE; INTERLEUKIN 2; IONOMYCIN; PROTEIN KINASE LCK; PROTEIN TYROSINE KINASE INHIBITOR; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; STAUROSPORINE; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

BINDING AFFINITY; CELL ACTIVITY; CYTOKINE RELEASE; DRUG BINDING; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IMMUNOMODULATION; REVIEW; STRUCTURE ANALYSIS; T LYMPHOCYTE;

ADJUVANTS, IMMUNOLOGIC; AMINES; BINDING, COMPETITIVE; CELLS, CULTURED; ENZYME INHIBITORS; HUMANS; INTERLEUKIN-2; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 1642371632     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/0929867043455710     Document Type: Review

References (20)

1. Kefalas, P.; Brown, T.R.; Brickell P.M. Int. J. Biochem. Cell Biol. 1995, 27, 551.
2. Molina, T.J.; Kishimara, K.: Paige, C.J.; Hartman, K.U.; Veillette, A.; Mak, T. W. Nature 1992, 357, 161.
3. Lowell, C.A.; Soriano, P. Genes and Development 1996, 10. 1845.
4. Appleby, M.W.; Gross, J.A.; Cooke, M.P.; Levin, S.D.; Quian, S.; Perlmutter, R.M. Cell 1992, 70, 751.
5. Stein, P.L.; Lee, H.M.; Rich, S.; Soriano, P. Cell 1992, 70, 741.
6. Goldberg, D.R.; Butz, T.; Cardozo, M.G.; Eckner, R.J.; Hammach, A.; Huang, J.; Jakes, S.; Kapadia, S.; Kashem, M.; Lukas, S.; Morwick, T.M.; Panzenbeck, M.; Patel, U.; Pav, S.; Peet, G.W.; Peterson, J.D.; Prokopowicz III, A.S.; Snow, R.J., Sellati, R., Takahashi, H.; Tan, J.; Tschantz, M.A.; Wang, W-J.; Wolak, J.; Xiong, P.; Moss, N.; J. Med. Chem. 2003, 46, 1337-1349.
7. Calderwood, D.J.; Johnston, D.N; Munschauer, R; Rafferty, P; Bioorg. Med. Chem. Lett. 2002, 12, 1683-1686.
8. Burchat, A.F.; Calderwood, D.J.; Friedman, M.M.; Hirst, G.C.; Biqin Li; Rafferty, P; Ritter, K.; Skinner, B.S.; Biorg. Med. Chem. Lett. 2002, 12, 1687-1690.
9. Chen, P; Iwanowicz, E.J.; Norris, D.; Gu, H.H.; Lin, J.; Moquin, R. V.; Das, J.; Wityak, J; Spergel, S.H.; de Fex, H.; Pang, S; Pitt, S.; Shen, D.R.; Schieven, G.L.; Barrish, J.C.; Biorg. Med. Chem. Lett. 2002, 12, 3153-3156.
10. Snow, R.J., Cardozo, M.G.; Morwick, T.M.; Busaca, C.A.; Dong, Y.; Eckner, R.J.; Jacober, S.; Jakes, S.; Kapadia, S.; Lukas, S.; Panzenbeck M.; Peet, G.W.; Peterson, J.D.; Prokopowicz III, A.S.; Sellati, R.; Tolbert, R.M.; Tschantz, M.A.; Moss, N.; J. Med. Chem. 2002, 45, 3394-3405.
11. Dowden, J; Ward, S.G. Exp. Opin. Ther. Patents 2001, 11, 295-306.
12. Davis, P,D.; Davis, J.D.; Hutchings, M.C.; Moffat, D.; International Patent Specification No. 97/19065.
13. Daves, G.D.; O'Brien, D.E.; Lewis, L.R.; Cheng, C.C. J. Heterocyclic Chem. 1964, 1, 130-133.
14. Spana, C.; O'Rourke, E.C.; Bolen, J.B.; Fargnoli, J. Protein Expression and Purification 1993, 4, 190.
15. Zimermann, J.; Caravatti, G.; Mett, H.; Meyer, T.; Müller, M.; Lydon, N.B.; Fabbro, D. Arch. Pharm, Pharm. Med. Chem., 1996, 329, 371-376.
16. Sicheri, F.; Moarefi, I; Kuriyan, J. Nature 1997, 385, 602-609.
17. Blundell, T. L., Carney, D. P., Gardner, S., Hayes, F. R. F., Howlin, B., Hubbard, T. J. P., Overington, J. P., Singh, D. A., Sibanda, B. L. and Sutcliffe, M. Eur. J. Biochem. 1988, 172, 513-520; SYBYL, Tripos Inc., 1699 South Hanley Road, St. Louis, Missouri, 63144, USA.
18. Jones G.; Willett P.; Glen R.C.; Leach A.R.; Taylor R.; J. Mol. Biol. 1997, 267, 727-748; GOLD, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
19. Allen, R.A.; Rapecki, S.E.; In Novel Cytokine Inhibitors, Higgs, G.A., Henderson, B., Eds; Birkhauser: Basel; pp 43-82.
20. Rapecki, S.; Allen, R. J. Pharmacol. Exp. Ther. 2002, 303, 1325-1333.