EGFR tyrosine kinase inhibitor

Gefitinib (Iressa) EGFR tyrosine kinase inhibitor Third-line tumor — non-small ceU Irmg Phase II... 

Erlotinib (Tarceva) EGFR tyrosine kinase inhibitor Refractory non-smaU ceU lung cancer Randomized Phase III... 

Kitazaki T, Oka M, Nakamura Y et al. Gefitinib, an EGFR tyrosine kinase inhibitor, directly inhibits the function of P-glycoprotein in multidrug resistant cancer cells. Lung Cancer 2005 49 337-343. 

Wang SE, Narasanna A, Perez-Torres M et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 2006 10 25-38. 

Assefa, H., Kamath, S., Buolamwini, J.K. 3D-QSAR and Docking Studies on 4-An-ilinoquinazoline and 4-Anilinoquinoline Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors. 

Li J et al (2006) CYP3A Phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst 98 1714-1723... 

Traxler, R, Green, J., Mett, H., Sequin, U., and Furet, R, Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors isoflavones and 3-phenyl-4(lH)-quinolones, J. Med. Chem. 42, 1018, 1999. 

Category Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor Half-life 24 Hours... 

Pore N, Jiang Z, Gupta A, Cerniglia G, Kao GD, Maity A. EGFR tyrosine kinase inhibitors decrease VEGF expression by both hypoxia-inducible factor (HIF)-l-independent and HIF-1-dependent mechanisms. Cancer Res 2006 66 3197-3204. 

AstraZeneca s gefitinib (Iressa) s core structure is a quinazoline. It is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) indicated for the treatment of cancers. Several other protein kinase inhibitors also used the quinazoline ring as their core structure. They include OSI s erlotinib (Tarceva) and GSK s lapatinib (Tykerb). 

Makawana JA, Sangani CB, Lin L, Zhu HL. Schiff s base derivatives bearing nitroi-midazole and quinoline nuclei new class of anticancer agents and potential EGFR tyrosine kinase inhibitors. Bioorg Med Chem Lett 2014 24(7) 1734-6. 

Lin R, Johnson S. G, Connolly P. J, Wetter S. K, Binnun E, Hughes T. V, Murray W. V, Pandey N. B, Moreno-Mazza S. J, Adams M, Fuentes-Pesquera A. R, Middleton S. A. Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, Bioorg. Med. Chem. Lett. 2009. p. 2333 - 2337. DOI 10.1016/j.bmcl.2009.02.067... 

A similar three-step procedure was used by Ban et al. in their synthesis of 58 from 57 on the route to 4-anilinoquinazolones, which were evaluated as EGFR tyrosine kinase inhibitors. The overall yield was reported to be 70% for this three-step transformation. 

Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d]pyrimidines analogs as antitumor EGFR tyrosine kinase inhibitors... 

Desulfurization of [ C]thiourea can also be accomplished by reduction with Raney-Ni in the presence of NH4OAC, providing [ C]formamidine acetate in nearly quantitative yield . This was used in a reaction with 5-amino-2-fluoropyridine-4-carboxylic acid (71) to produce the carbon-14-labeled pyrido[3,4-d]pyrimidine 72, an intermediate in the synthesis of [ C]PD0205520 (73). an EGFR tyrosine kinase inhibitor. 

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