651
Views
13
CrossRef citations to date
0
Altmetric
Research Article

A quantitative structure-activity relationship study of novel, potent, orally active, selective VEGFR-2 and PDGFRα tyrosine kinase inhibitors: Derivatives of N-Phenyl-N′-{4-(4-quinolyloxy)phenyl}urea as antitumor agents

, , &
Pages 168-173 | Received 17 Jan 2007, Accepted 01 Apr 2007, Published online: 04 Oct 2008

References

  • Folkman J. Anti-angiogenesis: New concept for therapy of solid tumors. Ann Surg 1972; 175: 409–416
  • Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels and pulmonary metastases following tumor implantation, Cancer Res 1974; 34: 997–1004
  • Eckhardt SG. Angiogenesis inhibitors as cancer therapy. Hosp Pract 1999; 63–84
  • Bergers G, Javaherian K, Lo K-M, Folkman J, Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 1999; 284: 808–812
  • Fan T-PD, Jaggar R, Bicknell R. Controlling the vasculature: Angiogenesis, antiangiogenesis and vascular targeting of gene therapy. Trends Pharmacol Sci 1995; 16: 57–66
  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993; 362: 841–844
  • Kolch W, Martiny-Baron G, Kieser A, Marme D. Regulation of the expression of VEGF/VPS and its receptors: Role in tumor angiogenesis. Breast Cancer Res Treat 1995; 36: 139–155
  • Leenders WPJ. Targetting VEGF in anti-angiogenic and anti-tumor therapy: Where are we now?. Int J Exp Pathol 1998; 79: 339–346
  • Strawn LM, McMahon G, App H, Schreck R, Kuchler WR, Longhi MP, Hui TH, Tang C, Levitzki A, Gazit A, Chen I, Keri G, Orfi L, Risau W, Flamme I, Ullirich A, Hirth KP, Shawver LK. Fik-1 as a target for tumor growth inhibition. Cancer Res 1996; 56: 3540–3545
  • Millauer B, Longhi MP, Plate KH, Shawver LK, Risau W, Ullrich A, Strawn LM. Dominant-negative inhibition of Fik-1 suppresses the growth of many tumor types in vivo. Cancer Res 1996; 56: 1615–1620
  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993; 362: 841–844
  • Prewett M, Huber J, Li Y, Santiago A, O'Connor W, King K, Overholser J, Hopper A, Pytowski B, Witte L, Bohlen P, Hicklin DJ. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999; 59: 5209–5218
  • Dumas J. Protein kinase inhibitors: Emerging pharmacophores 1997–2000. Exp Opin Ther Pat 2001; 11: 405–429
  • Connell RD, Beebe JS. Patent focus on cancer chemotherapeutics. II Angiogenesis agents: April 2000–September 2000. Exp Opin Ther Pat 2001; 11: 77–114
  • Sun L, Tran N, Tang F, App H, Hirth P, McMahon G, Tang C. Synthesis and biological evaluations of 3-substituted Indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem 1998; 41: 2588–2603
  • Fong TAT, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Fik-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization and growth of multiple tumor types. Cancer Res 1999; 59: 99–106
  • Sun L, Tran N, Liang C, Tang F, Rice A, Schreck R, Waltz K, Shawver LK, McMahon G, Tang C. Design, synthesis and evaluation of substituted 3-[(3- or 4-carboxyethyl-pyrrol-2-yl)methyidenyl]indolin-2-ones as inhibitors of VEGF, FGF and PDGF receptor tyrosine kinases. J Med Chem 1999; 42: 5120–5130
  • Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M, Schlessinger J, Ullrich A, Hubbard SR, Blake RA, Fong TAT, Strawn LM, Sun L, Tang C, Hawtin R, Tang F, Shenoy N, Hirth KP, McMahon G, Cherrington JM. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000; 60: 4152–4160
  • Hennequin LF, Thomas AP, Johnstone CE, Stokes ESE, Ple P, Lohmann J-JM, Ogilvie DJ, Dukes M, Wedge SR, Curwen JO, Kendrew J, Lambert-van-der-Brempt C. Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J Med Chem 1999; 42: 5369–5389
  • Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Curwen JO, Hennequin LF, Thomas AP, Stokes ESE, Curry B, Richmond GH, Wadsworth PF. ZD4190: An orally active inhibitor of vascular endothelial growth factor signaling with broadspectrum antitumor efficacy. Cancer Res 2000; 60: 970–975
  • Hennequin LF, Stokes ESE, Thomas AP, Johnstone C, Ple P, Ogilvie DJ, Dukes M, Wedge SR, Kendrew J, Curwen JO. Novel 4-anilinoquinazolines with C-7 basic side chains: Design and structure-activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J Med Chem 2002; 45: 1300–1312
  • Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ESE, Curry B, Richmond GHP, Wadsworth PF, Bigley AL, Hennequin LF. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002; 62: 4645–4655
  • Bold G, Altmann K-H, Frei J, Lang M, Manley PW, Traxler P, Wietfeld B, Bruggen J, Buchdunger E, Cozens R, Ferrari S, Furet P, Hofmann F, Martiny-Baron G, Mestan J, Rosel J, Sills M, Stover D, Acemoglu F, Boss E, Emmenegger R, Lasser L, Masso E, Roth R, Schlachter C, Vetterli W, Wyss D, Wood JM. New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor driven angiogenesis. J Med Chem 2000; 43: 2310–2323
  • Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei, Hofmann F, Mestan J, Mett H, O'Reilly T, Persohn E, Rosel J, Schnell C, Stover D, Theuer A, Towbin H, Wenger F, Woods-Cook K, Menrad A, Siemeister G, Schirner M, Thierauch K-H, Schneider MR, Drevs J, Martiny-Baron G, Totzke F, Marme D. PTK787/ZK222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000; 60: 2178–2189
  • Fernand NH, Hurwitz HI. Inhibition of vascular endothelial growth factor in the treatment of colorectal cancer. Semin Oncol 2003; 39–50, 3 (Suppl 6)
  • Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber JD, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA. A randomized trial of bevacizumab, an antivascular endothelial growth factor antibody, for metastatic renal cancer. N Eng J Med 2003; 349: 427–434
  • Kubo K, Shimizu T, Ohyama S, Murooka H, Iwai A, Nakamura K, Hasegawa K, Kobayashi Y, Takahashi N, Takahashi K, Kato S, Izawa T, Isoe T. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: Synthesis, structure-activity relationships and antitumor activities of N-Phenyl-N′-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem 2005; 48: 1359–1366
  • Kubo K, Shimizu T, Ohyama S, Murooka H, Nishitoba T, Kato S, Kobayashi Y, Yagi M, Isoe T, Nakamura K, Osawa T, Izawa T. A novel series of 4-phenoxyquinolines:Potent and highly selective inhibitors of PDGF receptor autophosphorylation. Bioorg Med Chem Lett 1997; 23: 22935–22940
  • Yagi M, Kato S, Kobayashi Y, Kubo K, Ohyama S, Shimizu T, Nishitoba T, Isoe T, Nakamura K, Ohashi H, Kobayashi N, Iinuma N, Osawa T, Onose R, Osada H. Selective inhibition of platelet-derived growth factor (PDGF) receptor autophosphory- lation and PDGF-mediated cellular events by quinoline derivatives. Exp Cell Res 1997; 234: 285–292
  • Yagi M, Kato S, Kobayashi Y, Kobayashi N, Iinuma N, Nakamura K, Kubo K, Ohyama S, Murooka H, Shimizu T, Nishitoba T, Osawa T, Nagano N. Beneficial effects of a novel inhibition of platelet-derived growth factor receptor autophosphorylation in the rat with mesangial proliferative glomerulonephritis. Gen Pharmacol 1998; 31: 765–773
  • Kubo K, Ohyama S, Shimizu T, Takami A, Murooka H, Nishitoba T, Kato S, Yagi M, Kobayashi Y, Iinuma N, Isoe T, Nakamura K, Iijima H, Osawa T, Izawa T. Synthesis and structure-activity relationship for new series of 4-phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase. Bioorg Med Chem 2003; 11: 5117–5133
  • ChemDraw Ultra 6.0 and Chem 3D Ultra, Cambridge Soft Corporation, Cambridge, USA.
  • Hansch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lien EJ. Aromatic substituents constants for structure-activity correlations. J Med Chem 1973; 16: 1207–1216
  • Unger SH, Hansch C. Quantitative models of steric effects. Prog Phys Org Chem 1976; 12: 91–118
  • Hansh C, Leo A. Substituents constants for correlation analysis in chemistry and biology. John Wiley, New York 1979
  • Wold S. Validation of QSAR's. Quant Struct-Act Relat 1991; 10: 191–193
  • Singh P, Kumar Rajesh, Sharma BK. Quantitative structure-activity relationship study of 5-iodo- and diaryl-analogues of tubercidin: Inhibitors of adenosine kinase. J Enz Inhib Med Chem 2003; 18: 395–402

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.