Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 9, 2012, Pages 3208-3212

  Curtin, Michael L ^a   Frey, Robin R ^a   Heyman, H Robin ^a   Soni, Niru B ^a   Marcotte, Patrick A ^a   Pease, Lori J ^a   Glaser, Keith B ^a   Magoc, Terrance J ^a   Tapang, Paul ^a   Albert, Daniel H ^a   Osterling, Donald J ^a   Olson, Amanda M ^a   Bouska, Jennifer J ^a   Guan, Zhiwen ^a   Preusser, Lee C ^a   Polakowski, James S ^a   Stewart, Kent D ^a   Tse, Chris ^a   Davidsen, Steven K ^a   Michaelides, Michael R ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

ABT 348; Antitumor activity; Aurora kinase inhibitors; KDR kinase inhibitors; Pyrazoles; Thienopyridine ureas

Indexed keywords

ABT 348; ANTINEOPLASTIC AGENT; AURORA A KINASE; AURORA B KINASE; AURORA KINASE INHIBITOR; THIENOPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; UREA DERIVATIVE; VASCULOTROPIN; VASCULOTROPIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; DRUG SCREENING; EDEMA; ENZYME ACTIVE SITE; ENZYME INHIBITION; EXPERIMENTAL DOG; FEMALE; HUMAN; HUMAN CELL; HYDROGEN BOND; MAXIMUM PLASMA CONCENTRATION; MOLECULAR MODEL; MOUSE; NONHUMAN; PLASMA CLEARANCE; RAT; STRUCTURE ACTIVITY RELATION; TUMOR MODEL;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; HUMANS; MICE; PROTEIN KINASE INHIBITORS; PYRIDINES; UREA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84859831259     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.03.035     Document Type: Article

References (20)

1. T. Marumoto, D. Zhang, and H. Saya Nat. Rev. Cancer 5 2005 42
2. N. Matthews, C. Visintin, B. Hartzoulakis, A. Jarvis, and D.L. Selwood Expert Rev. Anticancer Ther. 6 2006 109
3. H. Yang, T. Burke, J. Dempsey, B. Diaz, E. Collins, J. Toth, R. Beckmann, and X. Ye FEBS Lett. 579 2005 3385
4. F. Girdler, K.E. Gascoigne, P.A. Eyers, S. Hartmuth, C. Crafter, K.M. Foote, N.J. Keen, and S.S. Taylor J. Cell Sci. 119 2006 3664
5. For a review of VEGF biology, see: N. Ferrara, H.P. Gerber, and J. LeCouter Nat. Med. 9 2003 669
6. For an overview of the most recently approved KDR inhibitor, see: H. Commander, G. Whiteside, and C. Perry Drugs 71 2011 1355
7. T. Fojo Oncologist 13 2008 277
8. D.B. Mendel, A.D. Laird, X. Xin, S.G. Louie, J.G. Christensen, G. Li, R.E. Schreck, T.J. Abrams, T.J. Ngai, L.B. Lee, L.J. Murray, J. Carver, E. Chan, K.G. Moss, J.O. Haznedar, J. Sukbuntherng, R.A. Blake, L. Sun, C. Tang, T. Miller, S. Shirazian, G. McMahon, and J.M. Cherrington Clin. Cancer Res. 9 2003 327
9. Y. Dai, K. Hartandi, Z. Ji, A.A. Ahmed, D.H. Albert, J.L. Bauch, J.J. Bouska, P.F. Bousquet, G.A. Cunha, K.B. Glaser, C.M. Harris, D. Hickman, J. Guo, J. Li, P.A. Marcotte, K.C. Marsh, M.D. Moskey, R.L. Martin, A.M. Olson, D.J. Osterling, L.P. Pease, N.B. Soni, K.D. Stewart, V.S. Stoll, P. Tapang, D.R. Reuter, S.K. Davidsen, and M.R. Michaelides J. Med. Chem. 50 2007 1584
10. H.R. Heyman, R.R. Frey, P.F. Bousquet, G.A. Cunha, M.D. Moskey, A.A. Ahmed, N.B. Soni, P.A. Marcotte, L.J. Pease, K.B. Glaser, M. Yates, J.J. Bouska, D.H. Albert, C.L. Black-Schaefer, P.J. Dandliker, K.D. Stewart, P. Rafferty, S.K. Davidsen, M.R. Micahelides, and M.L. Curtin Bioorg. Med. Chem. Lett. 17 2007 1246
11. Several Aurora inhibitors with measureable activity against KDR were disclosed after this work was completed. For one example, ENMD-2076, see: G.C. Fletcher, R.D. Brokx, T.A. Denny, T.A. Hembrough, S.M. Plum, W.E. Fogler, C.F. Sidor, and M.R. Bray Mol. Cancer Ther. 10 2011 126
12. Y. Dai, Y. Guo, R.R. Frey, Z. Ji, M.L. Curtin, A.A. Ahmed, D.H. Albert, L. Arnold, T. Barlozzari, J.L. Bauch, J.J. Bouska, P.F. Bousquet, G.A. Cunha, K.B. Glaser, J. Guo, J. Li, P.A. Marcotte, K.C. Marsh, M.D. Moskey, L.J. Pease, K.D. Stewart, V.S. Stoll, P. Tapang, N. Wishart, S.K. Davidsen, and M.R. Michaelides J. Med. Chem. 48 2005 6066
13. W.J. McClellan, Y. Dai, C. Abad-Zapatero, D.H. Albert, J.J. Bouska, K.B. Glaser, T.J. Magoc, P.A. Marcotte, D.J. Osterling, K.D. Stewart, S.K. Davidsen, and M.R. Michaelides Bioorg. Med. Chem. Lett. 21 2011 5620
14. For an improved synthesis of this intermediate, see: K.M. Engstrom, A.L. Baize, T.S. Franczyk, J.M. Kallemeyn, M.M. Mulhern, R.C. Rickert, and S. Wagaw J. Org. Chem. 74 2009 3849
15. O. Pelkonen, M. Turpeinen, J. Hakkola, P. Honkakoski, J. Hukkanen, and H. Raunio Arch. Toxicol. 82 2008 667
16. D.O. Nettleton, and H.J. Einolf Curr. Topics Med. Chem. 11 2011 382
17. R.J. Riley, K. Grime, and R. Weaver Expert Opin. Drug Metab. Toxicol. 3 2007 51
18. C. Jamieson, E.M. Moir, Z. Rankovic, and G. Wishart J. Med. Chem. 49 2006 5029
19. J.I. Vandenberg, B.D. Walker, and T.J. Campbell Trends Pharm. Sci. 22 2001 240
20. For a detailed summary of the preclinical in vivo characterization of inhibitor 2 in a broad range of tumor types, see: Donawho, C. K. et al. Clin. Cancer Res., to be submitted.