Novel inhibitors of the v-raf murine sarcoma viral oncogene homologue B1 (BRAF) based on a 2,6-disubstituted pyrazine scaffold

Journal of Medicinal Chemistry

Volumn 51, Issue 11, 2008, Pages 3261-3274

  Niculescu Duvaz, Ion ^a   Roman, Esteban ^a   Whittaker, Steven R ^b   Friedlos, Frank ^a   Kirk, Ruth ^b   Scanlon, Ian J ^a   Davies, Lawrence C ^a   Niculescu Duvaz, Dan ^a   Marais, Richard ^b   Springer, Caroline J ^c  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

2 (3,4,5 TRIMETHOXYPHENYLAMINO) 6 (3 ACETAMIDOPHENYL)PYRAZINE; B RAF KINASE; PYRAZINE DERIVATIVE;

ARTICLE; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; IC 50; MELANOMA; MOLONEY MURINE SARCOMA ONCOVIRUS; STRUCTURE ACTIVITY RELATION;

DATABASES, FACTUAL; HUMANS; MUTATION; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-RAF; PYRAZINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 44949256205     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070776b     Document Type: Article

References (23)

1. Wellbrock, C.; Karasarides, M.; Marais, R. The RAF proteins take center stage. Nat. Rev. Mol. Cell Biol. 2004, 5, 875-885.
2. Davies, H.; Bignell, G. R.; Cox, C.; Stephen, P.; et al. Mutation of the BRAF gene in human cancers. Nature 2002, 417, 949-954.
3. Tuveson, D. A.; Weber, B. L.; Herlyn, M. BRAF as a potential therapeutic target in melanoma and other malignancies. Cancer Cell 2003, 4, 95-98.
4. Garnett, M. J.; Marais, R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 2004, 4, 313-319.
5. Chiloeches, A.; Marais, R. Mitogen-activated protein kinase cascades as therapeutic targets in cancer. Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins; Humana Press Inc.: Totowa, NJ, 2002; pp 179-206.
6. Wood, E.; Crosby, R. M.; Dickerson, S.; Frye, S. V.; Griffin, R.; et al. A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity. Anti-Cancer Drug Des. 2001, 16, 1-6.
7. Hall-Jackson, C. A.; Eyers, P. A.; Cohen, P.; Boyle, F. T.; Hewitt, N.; et al. Paradoxical activation of Raf by a novel Raf inhibitor. Chem. Biol. 1999, 6, 559-568.
8. Wilhelm, S. M.; Carter, C.; Tang, L. Y.; Wilkie, D.; McNabola, A.; et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004, 64, 7099-7109.
9. Bollag, G.; Freeman, S.; Lyons, G. F.; Post, L. E. Raf pathway inhibition in oncology. Curr. Opin. Investig. Drugs 2004, 4, 1436-1441.
10. Smith, R. A.; Dumas, J.; Adnane, L.; Wilhelm, S. M. Recent advances in the research and development of RAF kinase inhibitors. Curr. Top. Med. Chem. 2006, 6, 1071-1089.
11. Batt, D. B.; Bold, G.; Kim, S.; Ramsey, T. M.; Sabio, M. L. Use of Isoquinoline Derivatives for Treating Cancer and MAP Kinase Related Diseases; Novartis AG: Basel, Switzerland, 2004; p 85.
12. Fink, C. A.; Perez, L. B.; Ramsey, T. M.; Yusuf, N.; Versace, R. W. 1,4-Disubstituted Isoquinoline Derivatives as RAF-Kinase Inhibitors Useful for the Treatment of Proliferative Diseases; Novartis AG: Basel, Switzerland, 2005; p 144.
13. Takle, A. K.; Brown, M. J. B.; Davies, S.; Dean, D. K.; Francis, G.; et al. The identification of potent and selective imidazole-based inhibitors of B-RAF kinase. Bioorg. Med. Chem. Lett. 2006, 16, 378-381.
14. King, A. J.; Patrick, D. R.; Batorsky, R. S.; Ho, M. L.; Do, H. T.; et al. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006, 66, 11100-11105.
15. Ahmad, T.; Eisen, T. Kinase inhibition with BAY 43-9006 in renal cell carcinoma. Clin. Cancer Res. 2004, 10, 6388S-6392S.
16. Niculescu-Duvaz, I.; Roman, E.; Wittaker, S. R.; Friedlos, F.; Kirk, R.; et al. Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead. J. Med. Chem. 2006, 49, 407-416.
17. Wan, P. T. C.; Garnett, M. J.; Roe, M. S.; Lee, S.; Niculescu-Duvaz, D.; et al. Mechanism of activation of of the RAF/ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004, 116, 855-867.
18. Liao, J. J.-L. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J. Med. Chem. 2007, 50, 409-424.
19. Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. Simple, efficient catalyst system for the palladium-catalyzed amination of aryl chlorides, bromides and triflates. J. Org. Chem. 2000, 65, 1158-1174.
20. Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. Amination reaction of aryl halides with nitrogen-containing reagents mediated by palladium/ imidazolium salts. J. Org. Chem. 2001, 66, 7729-7737.
21. Kotha, S.; Lahiri, K.; khashinath, D. Recent applications of the Suzuki-Miyaura cross coupling reactions in organic synthesis. Tetrahedron 2002, 58, 9633-9695.
22. Littke, A.; Fu, G. C. Palladium catalysed coupling reaction of aryl chlorides. Angew. Chem., Int. Ed. 2002, 41, 4176-4211.
23. Tokarski, J. S.; Newitt, J. A.; Chang, C. Y. J.; Cheng, J. D.; Witteking, M.; et al. The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against Imatinib-resistant ABL mutants. Cancer Res. 2006, 66, 5790-5797.