Browse > Article
http://dx.doi.org/10.12925/jkocs.2008.25.2.16

Synthesis and EGFR Inhibitory Activity of 6-Guanidinoquinazoline Derivatives  

Yoo, Kyung-Ho (Biomaterials Research Center, Korea Institute of Science and Technology)
Lee, Yeo-Ran (Biomaterials Research Center, Korea Institute of Science and Technology)
Publication Information
Journal of the Korean Applied Science and Technology / v.25, no.2, 2008 , pp. 240-251 More about this Journal
Abstract
The central role of tyrosine phosphorylation in cell proliferative signaling mechanisms provides another target for chemotherapy. The aim of this research is to develop new quinazoline derivatives that possess the inhibitory activity for depidermal growth factor receptor (EGFR) tyrosine kinase (TK) as protein kinase inhibitors. In this work, a series of new 4-anilino-6-guanidino-7-methoxyquinazoline derivatives (12a-l) were synthesized by the introduction of guanidine moiety at C-6 of quinazoline nucleus and evaluated for their EGFR TK inhibitory activities.
Keywords
quinazolines; synthesis; EGFR TK; inhibitory activity;
Citations & Related Records
연도 인용수 순위
  • Reference
1 A. C. Porter and R. R. Vaillancourt, Tyrosine Kinase Receptor-activated Signal Transduction Pathways Which Lead to Oncogenesis, Oncogene, 17, 1343 (1998)   DOI   ScienceOn
2 P. Blume-Jensen and Tony Hunter, Oncogenic Kinase Signalling, Nature, 411, 355 (2001)   DOI   ScienceOn
3 D. Raben, B. A. Helfrich, D. Chan, G. Johnson, and P. A. Bunn, Jr., ZD1839, A Selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Alone and in Combination with Radiation and Chemotherapy as a New Therapeutic Strategy in Non-small Cell Lung Cancer, Semin. Oncol., 29 (Supplement 4), 37 (2002)   DOI   ScienceOn
4 Burris H. A. 3rd, Hurwitz H. I., Dees E. C., Dowlati A., Blackwell K. L., O'Neil B., Marcom P. K., Ellis M. J., Overmoyer B., Jones S. F., Harris J. L., Smith D. A., Koch K. M., Stead A., Mangum S., and Spector N. L., Phase I Safety, Pharmacokinetics, and Clinical Activity Study of Lapatinib (GW572016), A Reversible Dual Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinases, in Heavily Pretreated Patients with Metastatic Carcinomas, J Clin. Oncol., 23, 5305 (2005)   DOI   ScienceOn
5 O. Tabarrini, V. Cecchetti, A. Fravolini, G. Nocentini, A. Barzi, S. Sabatini, H. Miao, and C. Sissi, Design and Synthesis of Modified Quinolones as Antitumoral Acridones, J. Med. Chem., 42, 2136 (1999)   DOI   ScienceOn
6 P. Traxler and P. Furet, Strategies toward the Design of Novel and Selective Protein Tyrosine Kinase Inhibitors, Pharmacol. Ther., 82, 195 (1999)   DOI   ScienceOn
7 R. Perez-Soler, A. Chachoua, L. A. Hammond, E. K. Rowinsky, M. Huberman, D. Karp, J. Rigas, G. M. Clark, P. Santabarbara, and P. Bonomi, Determinants of Tumor Response and Survival with Erlotinib in Patients with Non-Small-Cell Lung Cancer, J. Clin. Oncol., 22, 3238 (2004)   DOI   ScienceOn
8 A. Levitzki, Protein Tyrosine Kinase Inhibitors as Therapeutic Agents, Pharmacol. Ther., 82, 231 (1999)   DOI   ScienceOn
9 C. C. Price, N. J. Leonard, and D. Y. Curtin, 4-(4'-Diethylamino-1'- methylbutylamino)-7-chloroquinazoline, J. Amer. Chem. Soc. 68, 1305 (1946)   DOI
10 B. Moy, P. Kirkpatrick, S. Kar, and P. Goss, Lapatinib, Nature Rev. Drug Discov. 6, 431 (2007)   DOI   ScienceOn
11 D. W. Fry, A. J. Kraker, A. McMichael, L. A. Ambroso, J. M. Nelson, W. R. Leopold, R. W. Connors, and A. J. Bridges, A Specific Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, Science, 265, 1093 (1994)   DOI
12 R. Tibes, J. Trent, and R. Kurzrock, Tyrosine Kinase Inhibitors and the Dawn of Molecular Cancer Therapeutics, Ann. Rev. Pharmacol. Toxicol., January 6, 2005
13 J. Vesel, L. Havlicek, M. Strnad, J. J. Blow, A. Donella-Deana, L. Pinna, D. S. Letham, J.-y. Kato, L. Detkvaud, S. Leclerc, and L. Meijere, Inhibition of Cyclin-dependent Kinases by Purine Analogues, Eur. J. Biochem., 224, 771 (1994)   DOI   ScienceOn
14 E. Weisberg, P. Manley, J. Mestan, S. Cowan-Jacon, A. Ray, and D. Griffin, AMN107 (nilotinib): A Novel and Selective Inhibitor of BCR-ABL. Brit. J. Canver, 94, 1765 (2006)   DOI   ScienceOn
15 J. Parrick and R. Ragunathan, Studies of Phthalazine-5,8-quinone, A Ring Contraction, and Some Novel and Potentially Useful Fluorescent Phthalimides, J. Chem. Soc., Perkin Trans. 1, 211 (1993)
16 A. J. Bridges, H. Zhou, D. R. Cody, G. W. Rewcastle, A. McMichael, H. D. H. Showalter, D. W. Fry, A. J. Kraker, and W. A. Denny, Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure-Activity Relationship for Analogues of 4- (3-Bromoanilino)-6,7-dimethoxyquinazoline (PD153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor, J. Med. Chem., 39, 267 (1996)   DOI   ScienceOn