A chemical tuned strategy to develop novel irreversible EGFR-TK inhibitors with improved safety and pharmacokinetic profiles

Journal of Medicinal Chemistry

Volumn 57, Issue 23, 2014, Pages 9889-9900

  Xia, Guangxin ^b   Chen, Wenteng ^a   Zhang, Jing ^b   Shao, Jiaan ^a   Zhang, Yong ^b   Huang, Wei ^a   Zhang, Leduo ^b   Qi, Weixing ^a   Sun, Xing ^b   Li, Bojun ^b   Xiang, Zhixiong ^b   Ma, Chen ^b   Xu, Jia ^b   Deng, Hailin ^b   Li, Yufeng ^b   Li, Ping ^b   Miao, Hong ^b   Han, Jiansheng ^b   Liu, Yanjun ^b   Shen, Jingkang ^b,c   Yu, Yongping ^a   more..

^a ZHEJIANG UNIVERSITY   (China)

^b Central Research Institute   (China)

^c SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AFATINIB; ANTINEOPLASTIC AGENT; CANERTINIB; CISAPRIDE; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; GEFITINIB; GLUTATHIONE; JANUS KINASE 2; N [4 ([3 CHLORO 4 FLUOROPHENYL)AMINO] 7 METHOXYQUINAZOLIN 6 YL] 2 FLUORO 4 (PIPERADIN 1 YL)BUT 2 ENAMIDE; N [4 ([3 CHLORO 4 FLUOROPHENYL)AMINO] 7 METHOXYQUINAZOLIN 6 YL] 4 (DIMETHYLAMINO) 2 FLUOROBUT 2 ENAMIDE; N [4 [(3 CHLORO 4 FLUOROPHENYL)AMINO] 7 ((TETRAHYDROFURAN 3 YL)OXY)QUINAZOLIN 6 YL] 4 (4 DIMETHYLAMINO) 2 FLUOROBUT 2 ENAMIDE; N [4 [(3 CHLORO 4 FLUOROPHENYL)AMINO] 7 METHOXYQUINAZOLIN 6 YL] 2 FLUORO 4 (PIPERIDIN 1 YL)BUT 2 ENAMIDE; N [4 [(3 CHLORO 4 FLUOROPHENYL)AMINO] 7 [(TETRAHYDROFURAN 3 YL)OXY]QUINAZOLIN 6 YL] 2 FLUORO 4 (PIPERIDIN 1 YL)BUT 2 ENAMIDE; N [4 [[3 CHLORO 4 (PYRIDIN 2 YL)METHOXY]PHENYL]AMINO 7 ETHOXY QUINAZOLIN 6 YL] 4 (DIMETHYLAMINO) 2 FLUOROBUT 2 ENAMIDE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; KCNH1 PROTEIN, HUMAN; POTASSIUM CHANNEL HERG; PROTEIN KINASE INHIBITOR;

ANIMAL EXPERIMENT; ANTIPROLIFERATIVE ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CELL CULTURE; COLON CANCER; CYTOTOXICITY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG POTENCY; DRUG SAFETY; DRUG UPTAKE; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; MICHAEL ADDITION; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; PHARMACOKINETICS; RAT; TUMOR REGRESSION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; LUNG NEOPLASMS; METABOLISM; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; LUNG NEOPLASMS; MICE, INBRED BALB C; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84918509634     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5014659     Document Type: Article

References (27)

1. Yarden, Y.; Sliwknowski, M. X. Untangling the ErbB signalling network Nature Rev. Mol. Cell. Biol. 2001, 2, 127-137
2. Hynes, N. E.; Lane, H. A. ErbB receptors and cancer: the complexity of targeted inhibitors Nature Rev. Cancer 2005, 5, 341-354
3. Ciardiello, F.; Tortora, G. EGFR antagonists in cancer treatment N. Engl. J. Med. 2008, 358, 1160-1174
4. Roskoski, R., Jr. Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition Pharmacol. Res. 2013, 68, 68-94
5. Maemondo, M.; Inoue, A.; Kobayashi, K.; Oizumi, S.; Isobe, H.; Saijo, Y.; Hagiwara, K.; Gemma, A.; Nukiwa, T.; Kudoh, S.; Kanazawa, M.; Nagao, K.; Nakai, Y.; Shibuya, M.; Akie, K.; Chonabayashi, N.; Hasegawa, Y.; Hayashibara, K.; Hino, M.; Hino, T.; Ikebuchi, K.; Ishii, Y.; Kaneko, N.; Kimura, Y.; Koba, H.; Kojima, T.; Kosaihira, S.; Koyama, N.; Miki, H.; Minegishi, Y.; Morikawa, N.; Moriyama, G.; Murayama, Y.; Nagashima, M.; Niizuma, K.; Nitanai, H.; Ogura, S.; Okamoto, Y.; Osaki, Y.; Sakai, H.; Sugita, H.; Suzuki, T.; Tanaka, J.; Tokunaga, H.; Tsukamoto, T.; Uematsu, K.; Usui, K.; Yasuda, K. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR N. Engl. J. Med. 2010, 362, 2380-2388
6. Rosell, R.; Carcereny, E.; Gervais, R.; Vergnenegre, A.; Massuti, B.; Felip, E.; Palmero, R.; Garcia-Gomez, R.; Pallares, C.; Sanchez, J. M.; Porta, R.; Cobo, M.; Garrido, P.; Longo, F.; Moran, T.; Insa, A.; De Marinis, F.; Corre, R.; Bover, I.; Illiano, A.; Dansin, E.; de Castro, J.; Milella, M.; Reguart, N.; Altavilla, G.; Jimenez, U.; Provencio, M.; Moreno, M. A.; Terrasa, J.; Muñoz-Langa, J.; Valdivia, J.; Isla, D.; Domine, M.; Molinier, O.; Mazieres, J.; Baize, N.; Garcia-Campelo, R.; Robinet, G.; Rodriguez-Abreu, D.; Lopez-Vivanco, G.; Gebbia, V.; Ferrera-Delgado, L.; Bombaron, P.; Bernabe, R.; Bearz, A.; Artal, A.; Cortesi, E.; Rolfo, C.; Sanchez-Ronco, M.; Drozdowskyj, A.; Queralt, C.; de Aguirre, I.; Ramirez, J. L.; Sanchez, J. J.; Molina, M. A.; Taron, M.; Paz-Ares, L. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomized phase 3 trial Lancet Oncol. 2012, 13, 239-246
7. Kobayashi, S.; Boggon, T. J.; Dayaram, T.; Jänne, P. A.; Kocher, O.; Meyerson, M.; Johnson, B. E.; Eck, M. J.; Tenen, D. G.; Halmos, B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib N. Engl. J. Med. 2005, 352, 786-792
8. Lee, J. K.; Shin, J. Y.; Kim, S.; Lee, S.; Park, C.; Kim, J. Y.; Koh, Y.; Keam, B.; Min, H. S.; Kim, T. M.; Jeon, Y. K.; Kim, D. W.; Chung, D. H.; Heo, D. S.; Lee, S. H.; Kim, J. I. Primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer harboring TKI-sensitive EGFR mutations: an exploratory study Ann. Oncol. 2013, 24, 2080-2087
9. Yun, C.-H.; Mengwasser, K. E.; Toms, A. V.; Woo, M. S.; Greulich, H.; Wong, K. K.; Meyerson, M.; Eck, M. J. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 2070-2075
10. Kwak, E. L.; Sordella, R.; Bell, D. W.; Godin-Heymann, N.; Okimoto, R. A.; Brannigan, B. W.; Harris, P. L.; Driscoll, D. R.; Fidias, P.; Lynch, T. J.; Rabindran, S. K.; McGinnis, J. P.; Wissner, A.; Sharma, S. V.; Isselbacher, K. J.; Settleman, J.; Haber, D. A. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 7665-7670
11. Bowles, D. W.; Weickhardt, A.; Jimeno, A. Afatinib for the treatment of patients with EGFR-positive non-small cell lung cancer Drugs Today 2013, 49, 523-535
12. Wissner, A.; Overbeek, E.; Reich, M. F.; Brawner Floyd, M.; Johnson, B. D.; Mamuya, N.; Rosfjord, E. C.; Discafani, C.; Davis, R.; Shi, X.; Rabindran, S. K.; Gruber, B. C.; Ye, F.; Hallett, W. A.; Nilakantan, R.; Shen, R.; Wang, Y.-F.; Greenberger, L. M.; Tsou, H.-R. Synthesis and structure-activity relationships of 6, 7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER-2) J. Med. Chem. 2003, 46, 49-63
13. Schwartz, P. A.; Kuzmic, P.; Solowiej, J.; Bergqvist, S.; Bolanos, B.; Almaden, C.; Nagata, A.; Ryan, K.; Feng, J.; Dalvie, D.; Kath, J. C.; Xu, M.; Wani, R.; Murray, B. M. Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 173-178
14. Serafimova, I. M.; Pufall, M. A.; Krishnan, S.; Duda, K.; Cohen, M. S.; Maglathlin, R. L.; McFarland, J. M.; Miller, R. M.; Frödin, M.; Taunton, J. Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles Nature Chem. Biol. 2012, 8, 471-476
15. Miller, R. M.; Paavilainen, V. O.; Krishnan, S.; Serafimova, I. M.; Taunton, J. Electrophilic fragment-based design of reversible covalent kinase inhibitors J. Am. Soc. Chem. 2013, 135, 5298-5301
16. Nonoo, R. H.; Armstrong, A.; Mann, D. J. Kinetic template-guided tethering of fragments ChemMedChem 2012, 7, 2082-2086
17. Bohm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Obst-Sander, U.; Stahl, M. Fluorine in medicinal chemistry ChemBiolChem 2004, 5, 637-643
18. Kirk, K. L. Fluorine in medicinal chemistry: recent therapeutic applications of fluorinated small molecules J. Fluorine Chem. 2006, 127, 1013-1029
19. Hagmann, W. K. The many roles for fluorine in medicinal chemistry J. Med. Chem. 2008, 51, 4359-4369
20. Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery J. Med. Chem. 2014, 57, 2832-2842
21. Rewcastle, G. W.; Palmer, B. D.; Bridges, A. J.; Showalter, H. D.; Sun, L.; Nelson, J.; McMichael, A.; Kraker, A. J.; Fry, D. W.; Denny, W. A. Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor J. Med. Chem. 1996, 39, 918-928
22. Wu, J.; Chen, W.; Xia, G.; Zhang, J.; Shao, J.; Tan, B.; Zhang, C.; Yu, W.; Weng, Q.; Liu, H.; Hu, M.; Deng, H.; Hao, Y.; Shen, J.; Yu, Y. Design, synthesis, and biological evaluation of novel conformationally constrained inhibitors targeting EGFR ACS Med. Chem. Lett. 2013, 4, 974-978
23. Kajjout, M.; Zemmouri, R.; Eddarir, S.; Rolando, C. An efficient access to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes by Horner-Wadsworth-Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S -ethyl ester followed by reduction with sodium borohydride Tetrahedron 2012, 68, 3225-3230
24. Gansäuer, A.; Worgull, D.; Knebel, K.; Huth, I.; Schnakenburg, G. 4-Exo cyclizations by template Angew. Chem., Int. Ed. 2009, 48, 8882-8885
25. Short, K. M.; Pham, S. M.; Williams, D. C.; Datta, S. Multisubstituted aromatic compounds as inhibitors of thrombin. WO 2011/126903, 2011.
26. Barf, T.; Kaptein, A. Irreversible protein kinase inhibitors: balancing the benefits and risks J. Med. Chem. 2012, 55, 6243-6644
27. 3H]dofetilide binding assay is a predictive screening tool for hERG blockade and proarrhythmia: Comparison of intact cell and membrane preparations and effects of altering [K+]o J. Pharmacol. Toxicol. Methods 2004, 50, 187-199