About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 154856, 9 pages
http://dx.doi.org/10.1155/2013/154856
Research Article

1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modelling Studies

1Centro de Química, Escola de Ciências, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
2CIQ/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
3Departamento de Bioquímica (U38-FCT), Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal
4Centro de Investigação de Montanha (CIMO), Escola Superior Agrária, Instituto Politécnico de Bragança, Campus de Santa Apolónia, Apartado 1172, 5301-855 Bragança, Portugal

Received 7 April 2013; Revised 12 June 2013; Accepted 13 June 2013

Academic Editor: Carmen Domene

Copyright © 2013 Pedro Soares et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Patan, “Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling,” Journal of Neuro-Oncology, vol. 50, no. 1-2, pp. 1–15, 2000. View at Publisher · View at Google Scholar · View at Scopus
  2. J. Folkman and Y. Shing, “Angiogenesis,” The Journal of Biological Chemistry, vol. 267, no. 16, pp. 10931–10934, 1992. View at Scopus
  3. N. Ferrara, H.-P. Gerber, and J. LeCouter, “The biology of VEGF and its receptors,” Nature Medicine, vol. 9, no. 6, pp. 669–676, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. M. A. Lemmon and J. Schlessinger, “Cell signaling by receptor tyrosine kinases,” Cell, vol. 141, no. 7, pp. 1117–1134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Baka, A. R. Clamp, and G. C. Jayson, “A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis,” Expert Opinion on Therapeutic Targets, vol. 10, no. 6, pp. 867–876, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Eichholz, S. Merchant, and A. M. Gaya, “Anti-angiogenesis therapies: their potential in cancer management,” Oncology Targets Therapy, vol. 3, pp. 69–82, 2010.
  7. D. D. Hu-Lowe, H. Y. Zou, M. L. Grazzini et al., “Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3,” Clinical Cancer Research, vol. 14, no. 22, pp. 7272–7283, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. L. Cowey, G. Sonpavde, and T. E. Hutson, “New advancements and developments in treatment of renal cell carcinoma: focus on pazopanib,” OncoTargets and Therapy, vol. 3, pp. 147–155, 2010.
  9. Y. Dai, Y. Guo, R. R. Frey et al., “Thienopyrimidine ureas as novel and potent multitargeted receptor tyrosine kinase inhibitors,” Journal of Medicinal Chemistry, vol. 48, no. 19, pp. 6066–6083, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. H. R. Heyman, R. R. Frey, P. F. Bousquet et al., “Thienopyridine urea inhibitors of KDR kinase,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 5, pp. 1246–1249, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Claridge, F. Raeppel, M.-C. Granger et al., “Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 9, pp. 2793–2798, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Raeppel, S. Claridge, O. Saavedra et al., “N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 5, pp. 1323–1328, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. O. Saavedra, S. Claridge, L. Zhan et al., “N3-Arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 24, pp. 6836–6839, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. “Staurosporine IC50 calculated by Invitrogen with the same FRET-based VEGFR-2 enzymatic kit used in this study,” http://tools.invitrogen.com.
  15. R. Costa, Â. Carneiro, A. Rocha et al., “Bevacizumab and ranibizumab on microvascular endothelial cells: a comparative study,” Journal of Cellular Biochemistry, vol. 108, no. 6, pp. 1410–1417, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Rocha, I. Azevedo, and R. Soares, “Anti-angiogenic effects of imatinib target smooth muscle cells but not endothelial cells,” Angiogenesis, vol. 10, no. 4, pp. 279–286, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. G. M. Morris, H. Ruth, W. Lindstrom et al., “Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility,” Journal of Computational Chemistry, vol. 30, no. 16, pp. 2785–2791, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. R. M. V. Abreu, H. J. C. Froufe, M. J. R. P. Queiroz, and I. C. F. R. Ferreira, “MOLA: a bootable, self-configuring system for virtual screening using AutoDock4/Vina on computer clusters,” Journal of Cheminformatics, vol. 2, no. 1, article 10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. “The PyMOL Molecular Graphics System, Version 1.3, Schrödinger, LLC,” September 2012, http://www.pymol.org/.