BRAF inhibitors based on an imidazo[4,5]pyridin-2-one scaffold and a meta substituted middle ring

Journal of Medicinal Chemistry

Volumn 53, Issue 5, 2010, Pages 1964-1978

  Nourry, Arnaud ^a   Zambon, Alfonso ^a   Davies, Lawrence ^a   Niculescu Duvaz, Ion ^a   Dijkstra, Harmen P ^a   Ménard, Delphine ^a   Gaulon, Catherine ^a   Niculescu Duvaz, Dan ^a   Suijkerbuijk, Bart M J M ^a   Manne, Frank Friedlos Helen A ^a   Kirk, Ruth ^a   Whittaker, Steven ^a   Marais, Richard ^a   Springer, Caroline J ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE INHIBITOR; BENZENE DERIVATIVE; FUSED CARBON NITROGEN SULFUR HETEROCYCLE; GEFITINIB; IMATINIB; IMIDAZO[4,5]PYRIDIN 2 ONE; PHOSPHOTRANSFERASE INHIBITOR; SORAFENIB; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; STRUCTURE ANALYSIS; SUBSTITUTION REACTION;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; HUMANS; IMIDAZOLES; INHIBITORY CONCENTRATION 50; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MODELS, MOLECULAR; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77949401354     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901509a     Document Type: Article

References (24)

1. Wellbrock, C.; Ogilvie, L.; Hedley, D.; Karasarides, M.; Martin, J.; Niculescu-Duvaz, D.; Springer, C. J.; Marais, R. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 2004, 64, 2338-2342.
2. Wellbrock, C.; Karasarides, M.; Marais, R. The RAF proteins take centre stage. Nat. Rev. Mol. Cell Biol. 2004, 5, 875-885.
3. Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M. J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B. A.; Cooper, C.; Shipley, J.; Hargrave, D.; Pritchard-Jones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G. J.; Bigner, D. D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J. W.; Leung, S. Y.; Yuen, S. T.; Weber, B. L.; Seigler, H. F.; Darrow, T. L.; Paterson, H.; Marais, R.; Marshall, C. J.; Wooster, R.; Stratton, M. R.; Futreal, P. A. Mutations of the BRAF gene in human cancer. Nature 2002, 417, 949-954.
4. Wan, P. T.; Garnett, M. J.; Roe, S. M.; Lee, S.; Niculescu-Duvaz, D.; Good, V. M.; Jones, C. M.; Marshall, C. J.; Springer, C. J.; Barford, D.; Marais, R. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004, 116, 855-867.
5. Gray-Schopfer, V.; Wellbrock, C.; Marais, R. Melanoma biology and new targeted therapy. Nature 2007, 445, 851-857.
6. Hingorani, S. R.; Jacobetz, M. A.; Robertson, G. P.; Herlyn, M.; Tuveson, D. A. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res. 2003, 63, 5198-5202.
7. Karasarides, M.; Chiloeches, A.; Hayward, R.; Niculescu-Duvaz, D.; Scanlon, I.; Friedlos, F.; Ogilvie, L.; Hedley, D.; Martin, J.; Marshall, C. J.; Springer, C. J.; Marais, R. B-RAF is a therapeutic target in melanoma. Oncogene 2004, 23, 6292-6298.
8. Roberts, P. J.; Der, C. J. Targeting the Raf-MEK-ERK mitogenactivated protein kinase cascade for the treatment of cancer. Oncogene 2007, 26, 3291-3310.
9. 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.
10. Barker, A. J.; Gibson, K. H.; Grundy, W.; Godfrey, A. A.; Barlow, J. J.; Healy, M. P.; Woodburn, J. R.; Ashton, S. E.; Curry, B. J.; Scarlett, L.; Henthorn, L.; Richards, L. Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg. Med. Chem. Lett. 2001, 11, 1911-1914.
11. Lowinger, T. B.; Riedl, B.; Dumas, J.; Smith, R. A. Design and discovery of small molecules targeting raf-1 kinase. Curr. Pharm. Des. 2002, 8, 2269-2278.
12. Capdeville, R.; Buchdunger, E.; Zimmermann, J.; Matter, A. Glivec (ST1571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discovery 2002, 1, 493-502.
13. Liu, Y.; Gray, N. S. Rational design of inhibitors that bind to inactive kinase conformations. Nat. Chem. Biol. 2006, 2, 358364.
14. Niculescu-Duvaz, D.; Gaulon, C.; Dijkstra, H. P.; NiculescuDuvaz, I.; Zambon, A.; Menard, D.; Suijkerbuijk, B. M.; Nourry, A.; Davies, L.; Manne, H.; Friedlos, F.; Ogilvie, L.; Hedley, D.; Whittaker, S.; Kirk, R.; Gill, A.; Taylor, R. D.; Raynaud, F. I.; Moreno-Farre, J.; Marais, R.; Springer, C. J. Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF). J. Med. Chem. 2009, 52, 2255-2264.
15. Menard, D.; Niculescu-Duvaz, I.; Dijkstra, H. P.; Niculescu-Duvaz, D.; Suijkerbuijk, B. M.; Zambon, A.; Nourry, A.; Roman, E.; Davies, L.; Manne, H. A.; Friedlos, F.; Kirk, R.; Whittaker, S.; Gill, A.; Taylor, R. D.; Marais, R.; Springer, C. J. Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. J. Med. Chem. 2009, 52, 3881-3891.
16. Liao, J.J. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J. Med. Chem. 2007, 50, 409-424
17. Tsai, J.; Lee, J. T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N. K.; Sproesser, K.; Li, L.; Smalley, K. S.; Fong, D.; Zhu, Y. L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.; Suzuki, Y.; Luu, C.; Settachatgul, C.; Shellooe, R.; Cantwell, J.; Kim, S. H.; Schlessinger, J.; Zhang, K. Y.; West, B. L.; Powell, B.; Habets, G.; Zhang, C.; Ibrahim, P. N.; Hirth, P.; Artis, D. R.; Herlyn, M.; Bollag, G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 3041-3046.
18. Correa, A.; Tellitu, I.; Dominguez, E.; SanMartin, R. Novel alternative for the N-S bond formation and its application to the synthesis of benzisothiazol-3-ones. Org. Lett. 2006, 8, 48114813.
19. Wang, J.; Rosingana, M.; Discordia, R. P.; Soundararajan, N.; Polniaszek, R. Aminolysis of esters or lactones promoted by NaHMDS, a general and efficient method for the preparation of Amaryl amides. Synlett 2001, 9, 1485-1487.
20. Davies, S. P.; Reddy, H.; Caivano, M.; Cohen, P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 2000, 351, 95-105.
21. Filippakopoulos, P.; Barr, A.; Fedorov, O.; Keates, T.; Soundararajan, M.; Elkins, J.; Salah, E.; Burgess-Brown, N.; Ugochukwu, E.; Pike, A. C. W.; Muniz, J.; Roos, A.; Chaikuad, A.; von Delft, F.; Arrowsmith, C. H.; Edwards, A. M.,; Weigelt, J.; Bountra, C.; Knapp, S. Crystal Structure of Human Mitogen Activated Protein Kinase 11 (p3 8 beta) in Complex with Nilotinib. Structural Genomics Consortium. PDB code: 3GP0 (http://www.rcsb.org/pdb/home/home.do), 2009.
22. Seeliger, M. A.; Nagar, B.; Frank, F.; Cao, X.; Henderson, M. N.; Kuriyan, J. c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. Structure 2007, 15, 299-311.
23. Jacobs, M. D.; Caron, P. R.; Hare, B. J. Classifying protein kinase structures guides use of ligand-selectivity profiles to predict inactive conformations: structure of lck/imatinib complex. Proteins 2008, 70, 1451-1460.
24. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.