Thienopyridine urea inhibitors of KDR kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 5, 2007, Pages 1246-1249

  Heyman, H Robin ^a   Frey, Robin R ^a   Bousquet, Peter F ^a   Cunha, George A ^a   Moskey, Maria D ^a   Ahmed, Asma A ^a   Soni, Niru B ^a   Marcotte, Patrick A ^a   Pease, Lori J ^a   Glaser, Keith B ^a   Yates, Melinda ^a   Bouska, Jennifer J ^a   Albert, Daniel H ^a   Black Schaefer, Candace L ^a   Dandliker, Peter J ^a   Stewart, Kent D ^a   Rafferty, Paul ^a   Davidsen, Steven K ^a   Michaelides, Michael R ^a   Curtin, Michael L ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

KDR kinase; Thienopyridine; Urea; VEGF

Indexed keywords

ESTRADIOL; UREA DERIVATIVE; VASCULOTROPIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; DRUG POTENCY; EDEMA; ENZYME ACTIVITY; ENZYME INHIBITION; MOUSE; NONHUMAN; SUBSTITUTION REACTION; UTERUS;

ANIMALS; DISEASE MODELS, ANIMAL; EDEMA; ESTRADIOL; FEMALE; MICE; MODELS, MOLECULAR; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; UREA; UTERINE DISEASES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 33846902851     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.12.015     Document Type: Article

References (19)

1. Hunter T. Cell 100 (2000) 113
2. Manning G., Whyte D.B., Martinez R., Hunter T., and Sudarsanam S. Science 298 (2000) 1912
3. Robinson D.R., Wu Y.M., and Lin S.F. Oncogene 19 (2000) 5548
4. Blume-Jensen P., and Hunter T. Nature 411 (2001) 355
5. Ferrara N., Gerber H.P., and LeCouter J. Nat. Med. 9 (2003) 669
6. Dvorak H.F. J. Clin. Oncol. 20 (2002) 4368
7. Morabito A., De Maio E., Di Maio M., Normanno N., and Perrone F. Oncologist 11 (2006) 753
8. Dai Y., Guo Y., Frey R.R., Ji Z., Curtin M.L., Ahmed A.A., Albert D.H., Arnold L., Barlozzari T., Bauch J.L., Bouska J.J., Bousquet P.F., Cunha G.A., Glaser K.B., Guo J., Li J., Marcotte P.A., Marsh K.C., Moskey M.D., Pease L.J., Stewart K.D., Stoll V.S., Tapang P., Wishart N., Davidsen S.K., and Michaelides M.R. J. Med. Chem. (2005) 6066
9. 50 values were determined using an ATP concentration of 1 mM as described in Ref. 7.
10. Miyazaki Y., Matsunaga S., Tang J., Maeda Y., Nakano M., Philippe R.J., Shibahara M., Liu W., Sato H., Wang L., and Nolte R.T. Bioorg. Med. Chem. Lett. 15 (2005) 2203
11. Burchat A.F., Calderwood D.J., Hirst G.C., Holman N.J., Johnston D.N., Munschauer R., Rafferty P., and Tometzki G.B. Bioorg. Med. Chem. Lett. 10 (2000) 2171
12. Burchat A.F., Calderwood D.J., Friedman M.M., Hirst G.C., Li B., Rafferty P., Ritter K., and Skinner B.S. Bioorg. Med. Chem. Lett. 12 (2002) 1687
13. Curtin M.L., Frey R.R., Heyman H.R., Sarris K.A., Steinman D.H., Holmes J.H., Bousquet P.F., Cunha G.A., Moskey M.D., Ahmed A.A., Pease L.J., Glaser K.B., Stewart K.D., Davidsen S.K., and Michaelides M.R. Bioorg. Med. Chem. Lett. 14 (2004) 4505
14. Dumas J., Smith R.A., and Lowinger T.B. Curr. Opin. Drug Discov. Dev. 7 (2004) 600
15. A related series of KDR inhibitors have recently been reported:. Miyazaki Y., Nakano M., Sato H., Truesdale A.T., Stuart J.D., Nartey E.N., Hightower K.E., and Kane-Carson L. Bioorg. Med. Chem. Lett. (2006) 10.1016/j.bmcl.2006.09.050
16. New J.S., Christorpher W.L., Yevich J.P., Butler R., Schlemmer R.F., VanderMaelen C.P., and Cipollina J.A. J. Med. Chem. 32 (1989) 1147
17. Toledo L.M., Lydon N.B., and Elbaum D. Curr. Med. Chem. 6 (1999) 775
18. 50 values represent inhibition of KDR phosphorylation in NIH3T3 cells stably transfected with full length human KDR. The procedure was followed as described in Ref. 12.
19. The computational analysis used to create this homology model with a recently published crystal structure of KDR-homolog KIT kinase (PDB entry 1T46) is described in Ref. 7.