Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 1, 2008, Pages 386-390

  Dai, Yujia ^a   Hartandi, Kresna ^a   Soni, Niru B ^a   Pease, Lori J ^a   Reuter, David R ^a   Olson, Amanda M ^a   Osterling, Donald J ^a   Doktor, Stella Z ^a   Albert, Daniel H ^a   Bouska, Jennifer J ^a   Glaser, Keith B ^a   Marcotte, Patrick A ^a   Stewart, Kent D ^a   Davidsen, Steven K ^a   Michaelides, Michael R ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

KDR; Pyrazolopyridines; VEGFR PDGFR kinase inhibitors

Indexed keywords

ABT 869; AMINE; PHOSPHOTRANSFERASE INHIBITOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE FYN; PROTEIN TYROSINE KINASE; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; STEM CELL FACTOR; UNCLASSIFIED DRUG; UREA DERIVATIVE; VASCULOTROPIN RECEPTOR; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; DISTRIBUTION VOLUME; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG SYNTHESIS; EDEMA; IC 50; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; AMINOPYRIDINES; ANIMALS; BIOLOGICAL AVAILABILITY; EDEMA; FEMALE; INHIBITORY CONCENTRATION 50; MICE; MODELS, MOLECULAR; PROTEIN KINASE INHIBITORS; PYRAZOLES; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; UREA; UTERINE DISEASES;

EID: 37549019605     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.10.018     Document Type: Article

References (18)

1. Carmeliet P., and Jain R.K. Nature 407 (2000) 249
2. Zetter B.R. Annu. Rev. Med. 49 (1998) 407
3. Ullrich A., and Schlessinger J. Cell 61 (1990) 203
4. Hubbard S.R., and Till J.H. Annu. Rev. Biochem. 69 (2000) 373
5. Bergland E.K. Am. J. Health-Syst. Pharm. 61 Suppl. 5 (2004) S4
6. Skobe M., and Fusenig N.E. Proc. Natl. Acad. Sci. USA 95 (1998) 1050
7. Lindahl P., Johansson B.R., Leveen P., and Betsholtz C. Science 277 (1997) 242
8. Lin E.Y., Nguyen A.V., Russell R.G., and Pollard J.W. J. Exp. Med. 193 (2001) 727
9. Stirewalt D.L., and Radich J.P. Nat. Rev. Cancer 3 (2003) 650
10. Demetri G.D. Semin. Oncol. 28 (2001) 19
11. Ferrara N., and Kerbel R.S. Nature 438 (2005) 967
12. Bilodeau M.T., Fraley M.E., and Hartman G.D. Expert Opin. Investig. Drugs 11 (2002) 737
13. Bergsland E.K. Am. J. Health-Syst. Pharm. 61 Suppl. 5 (2004) S12
14. Dai Y., Hartandi K., Ji Z., Ahmed A.A., Albert D.H., Bauch J.L., Bouska J.J., Bousquet P.F., Cunha G.A., Glaser K.B., Harris C.M., Hickman D., Guo J., Li J., Marcotte P.A., Marsh K.C., Moskey M.D., Martin R.L., Olson A.M., Ostering D.J., Pease L.J., Soni N.B., Stewart K.D., Stoll V.S., Tapang P., Reuter D.R., Davidsen S.K., and Michaelides M.R. J. Med. Chem. 50 (2007) 1584
15. Albert D.H., Tapang P., Magoc T.J., Pease L.J., Reuter D.R., Wei R.-Q., Li J., Guo J., Bousquet P.F., Ghoreish-Haack N.S., Wang B., Bukofzer G.T., Wang Y.-C., Stavropoulos J.A., Hartandi K., Niquette A.L., Soni N., Johnson E.F., McCall J.O., Bouska J.J., Luo Y., Donawho C.K., Dai Y., Marcotte P.A., Glaser K.B., Michaelides M.R., and Davidsen S.K. Mol. Cancer Ther. 5 (2006) 995
16. Kinase enzymatic assays were performed utilizing the homogeneous time-resolved fluorescence (HTRF) protocol in the presence of 1.0 mM ATP. For the detailed procedure, see Ref. 8.
17. For the procedure of the KDR cellular assay, see Ref. 8.
18. Dai Y., Guo Y., Frey R.R., Ji Z., Curtin M.L., Ahmed A.A., Albert D.H., Arnold L., Arries S.S., 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., Mosley M.D., Pease L.J., Stewart K.D., Stoll V.S., Tapang P., Wishart N., Davidsen S.K., and Michaelides M. J. Med. Chem. 48 (2005) 6066