N-(Aryl)-4-(azolylethyl)thiazole-5-carboxamides: Novel potent inhibitors of VEGF receptors I and II

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 3, 2006, Pages 602-606

  Kiselyov, Alexander S ^a   Piatnitski, Evgueni ^b   Semenova, Marina ^c   Semenov, Victor V ^d  

^a CHEMDIV INC   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c KOL TSOV INSTITUTE OF DEVELOPMENTAL BIOLOGY   (Russian Federation)

^d N D ZELINSKY INSTITUTE OF ORGANIC CHEMISTRY   (Russian Federation)

Author keywords

4 (Azolylethyl)thiazole 5 carboxamides; Angiogenesis; Dual kinase inhibitor; Receptor tyrosine kinase; Vascular endothelial growth factor receptor 2

Indexed keywords

PROTEIN TYROSINE KINASE; THIAZOLE; THIAZOLE DERIVATIVE; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2;

ARTICLE; CELL ASSAY; CONTROLLED STUDY; DRUG POTENCY; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; NONHUMAN; SUBSTITUTION REACTION;

AMIDES; ANIMALS; CHO CELLS; CRICETINAE; ENZYME INHIBITORS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; THIAZOLES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 29544444969     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.10.058     Document Type: Article

References (20)

1. M. Klagsbrun, and M.A. Moses Chem. Biol. 6 1999 R217
2. W. Risau Nature 386 1997 671
3. TM (Bevacizumab) has recently been approved to treat colorectal cancer see: C. Culy Drugs Today 41 2005 23
4. TM (Pegaptanib sodium) has recently been approved to treat neovascular age-related macular degeneration; see: S.L. Fine, D.F. Martin, and P. Kirkpatrick Nat. Rev. Drug Disc. 4 2005 187
5. G. Bold, K-H. Altmann, F. Jorg, M. Lang, P.W. Manley, P. Traxler, B. Wietfeld, J. Bruggen, E. Buchdunger, R. Cozens, S. Ferrari, F. Pascal, F. Hofmann, G. Martiny-Baron, J. Mestan, J. Rosel, M. Sills, D. Stover, F. Acemoglu, E. Boss, R. Emmenegger, L. Lasser, E. Masso, R. Roth, C. Schlachter, W. Vetterli, D. Wyss, and J.M. Wood J. Med. Chem. 43 2000 2310
6. L.F. Hennequin, E.S.E. Stokes, A.P. Thomas, C. Johnstone, P.A. Ple, D.J. Ogilvie, M. Dukes, S.R. Wedge, J. Kendrew, and J.O. Curwen J. Med. Chem. 45 2002 1300
7. S.R. Wedge, J. Kendrew, L.F. Hennequin, P.J. Valentine, S.T. Barry, S.R. Brave, N.R. Smith, N.H. James, M. Dukes, J.O. Curwen, R. Chester, J.A. Jackson, S.J. Boffey, L.L. Kilburn, S. Barnett, G.H.P. Richmond, P.F. Wadsworth, M. Walker, A.L. Bigley, S.T. Taylor, L. Cooper, S. Beck, J.M. Juergensmeier, and D.J. Ogilvie Cancer Res. 65 2005 4389
8. P.W. Manley, P. Furet, G. Bold, J. Brüggen, J. Mestan, T. Meyer, C. Schnell, and J. Wood J. Med. Chem. 45 2002 5697
9. P.W. Manley, G. Bold, G. Fendrich, P. Furet, J. Mestan, T. Meyer, B. Meyhack, A. Strauss, and J. Wood Cell. Mol. Biol. Lett. 8 2003 532
10. Altmann, K.-H.; Bold, G.; Furet, P.; Manley, P. W.; Wood, J. M.; Ferrari, S.; Hofmann, F.; Mestan, J.; Huth, A.; Krüger, M.; Seidelmann, D.; Menrad, A.; Haberey, M.; Thierauch, K.-H. U.S. Patent 6,878,720 B2, 2005.
11. E.L. Piatnitski, M. Duncton, R. Katoch-Rouse, D. Sherman, A.S. Kiselyov, D. Milligan, C. Balagtas, W. Wong, J. Kawakami, and J. Doody Bioorg. Med. Chem. 15 2005 4696
12. 3OS: C, 59.38; H, 4.10; N, 12.22. Found: C, 59.23; H, 4.21, N, 12.04.
13. 2, 2 mM DTT, and 1 mg/ml BSA) containing 0.5 mmol pGAT-biotin and 3-4 ng KDR enzyme was added to each well. After 5-10 min preincubation, the kinase reaction was initiated by the addition of 10 μl of 10 μM ATP in the reaction buffer, after which the plate was incubated at room temperature for 45 min. The reaction was stopped by addition of 50 μl KF buffer (50 mM Hepes, pH 7.5, 0.5 M KF, and 1 mg/ml BSA) containing 100 mM EDTA and 0.36 μg/ml PY20K (Eu-cryptate labeled anti-phosphotyrosine antibody, CIS Bio International) was added and after an additional 2 h incubation at RT, the plate was analyzed in a RUBYstar HTRF Reader.
14. M.A. McTigue, J.A. Wickersham, C. Pinko, R.E. Showalter, C.V. Parast, A. Tempczyk-Russell, M.R. Gehring, B. Mroczkowski, C.C. Kan, J.E. Villafranca, and K. Appelt Structure 7 1999 319
15. H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, and P.E. Bourne Nucleic Acids Res. 28 2000 235
16. D. Hanahan, and J. Folkman Cell 86 1996 353
17. J. Folkman, and M. Klagsburn Science 235 1987 442
18. I. Zachary Biochem. Soc. Trans. 31 2003 1171
19. F. Eskens Br. J. Cancer 90 2004 1
20. 4 and absorbance was measured at 450 nm.