The discovery of benzanilides as c-Met receptor tyrosine kinase inhibitors by a directed screening approach

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 18, 2011, Pages 5224-5229

  Allen, Joanne V ^a   Bardelle, Catherine ^a   Blades, Kevin ^a   Buttar, Dave ^a   Chapman, Louise ^a   Colclough, Nicola ^a   Dossetter, Alexander G ^a   Garner, Andrew P ^a   Girdwood, Alan ^a   Lambert, Christine ^a   Leach, Andrew G ^a   Law, Brian ^a   Major, John ^a   Plant, Helen ^a   Slater, Anthony M ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Benzanilides; Bio isosteres; c Met; Decisions; Directed screening; Kinase; Ligand efficiency; Secondary metabolism

Indexed keywords

ANILIDE; BENZENE DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; SCATTER FACTOR RECEPTOR; SCATTER FACTOR RECEPTOR INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SOLUBILITY; DRUG SYNTHESIS; ENZYME INHIBITION; LIVER CELL; NONHUMAN; PROCESS OPTIMIZATION; RAT; STRUCTURE ACTIVITY RELATION;

ANILIDES; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 80051950267     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.07.047     Document Type: Article

References (34)

1. For a review on c-Met and its role in cancer see, and reference therein: M. Sattler, and R. Salgia Curr. Oncol. Rep. 9 2 2007 102
2. C. Birchmeier, W. Birchmeier, E. Gherardi, and G.F. Vande Woude Nature Rev. 4 2003 915
3. K.M. Weidner, S.D. Cesare, M. Sachs, V. Brinkmann, J. Behrens, and W. Birchmeier Nature 384 1996 173
4. M. Sachs, H. Brohmann, D. Zechner, T. Muller, J. Hulsken, I. Walther, U. Schaeper, C. Birchmeier, and W. Birchmeier J. Cell Biol. 150 2000 1375
5. L. Vivanco, and C.L. Sawyers Nature Rev. 2002 489
6. D.P. Bottaro, J.S. Rubin, D.L. Faletto, A.M.-L. Chan, T.E. Kmiecik, G.F. Vande Woude, and S.A. Aaronson Science 251 1991 802
7. S. Potempa, and A.J. Ridley Mol. Biol. Cell 9 1998 2185
8. D.P. Bottaro, and L.A. Liotta Nature 423 2003 593
9. S. Pennacchietti, M. Michielli, M. Mazzone, S. Giordano, and P.M. Comoglio Cancer Cell 3 2003 347
10. For recent small molecule inhibitors of c-Met see: T.L. Underiner, T. Herbertz, and S.J. Miknyoczki Anti-Cancer Agents in Med. Chem. 10 2010 7
11. J.G. Christensen, R. Schreck, P. Kuruganti, E. Chan, P. Le, J. Chen, X. Wang, L. Ruslim, R. Blake, K.E. Lipson, J. Ramphal, S. Do, J.J. Cui, J.M. Cherrington, and D.B. Mendal Cancer Res. 63 2003 7345
12. M. Sattler, Y.B. Pride, P. Ma, J.L. Gramlich, S.C. Chu, S.S. Quinnan, C. Liang, K. Podar, J.G. Christensen, and R. Salgia Cancer Res. 63 2003 5462
13. G.M. Schroeder, Y. An, Z.-W. Cai, X.-T. Chen, C. Clark, L.A.M. Cornelius, J. Dai, J. Gullo-Brown, A. Gupta, B. Henley, J.T. Hunt, R. Jeyaseelan, A. Kamath, K. Kim, J. Lippy, L.J. Lombardo, V. Manne, S. Oppenheimer, J.S. Sack, R.J. Schmidt, G. Shen, K. Stenfanski, J.S. Tokarski, G.L. Trainer, B.S. Waulet, D. Wei, D.K. Williams, Y. Zhang, Y. Zhang, J. Fargnoli, and R.M. Borzilleri J. Med. Chem. 52 2009 1251
14. L. Liu, A. Siegmund, N. Xi, P. Kaplan-Lefko, K. Rex, A. Chen, J. Lin, J. Moriguchi, L. Berry, L. Huang, Y. Teffera, Y. Yang, Y. Zhang, S.F. Bellon, M. Le, R. Shimanovich, A. Bak, C. Dominguez, M.H. Norman, J.-C. Harmange, I. Dussault, and T.-S. Kim J. Med. Chem. 51 2008 3688
15. H.Y. Zou, L. Qiuhua, J.H. Lee, M.E. Arango, S.R. McDonnell, S. Yamazaki, T.B. Koudriakova, G. Alton, J. Cui, P.-P. Kung, M.D. Nambu, G. Los, S. Bender, B. Mroczkowski, and J.G. Christensen Cancer Res. 67 2007 4408
16. (a) See compound 13a within Dinsmore, C. J.; Jewell, J.P.; Katz, J. D.; Machacek, M. R.; Otte, R. D.; Young, J. R. PCT WO 2007/002258 A2
17. Katz, J. D. Discovery of a Unique Class of c-Met Inhibitors for the Treatment of Cancer. Presented at the 31st National Medicinal Chemistry Symposia, Pittsburgh, PA, June 2008, Pittsburgh, PA.
18. 'Privileged' refers to structural motifs that are known to bind into the ATP binding pocket of kinases, for example H-bond acceptor/donor pairs that mimic the purine group of ATP. Amides are known kinase inhibitors, for example: I. Baldwin, P. Bamborough, C.G. Haslam, S.S. Hunjan, T. Longstaff, C.J. Mooney, S. Patel, J. Quinn, and D.O. Somers Bioorg. Med. Chem. Lett. 18 2008 5285
19. 2, 0.1 mM sodium orthovanadate, 10 mM DTT & 0.1% BSA) was then added to all test wells. 5 μl of freshly diluted enzyme was added to all wells to start the reaction and the plates incubated at room temperature for 60 min. To stop the reaction 5 μl 'STOP' bead solution (50 μg/ml AlphaScreen (Perkin-Elmer, Product number 6760620 M) anti-phosphotyrosine-100 acceptor beads & 50 μg/ml streptavidin-coated AlphaScreen (Perkin-Elmer, Product number 6760620 M) were added. Plates were then sealed & incubated in the dark for 20 h, before being read using an AlphaQuest machine (Perkin-Elmer). 'Blank' (enzyme inhibited by EDTA) and 'total' (no compound) control values were used to determine the concentration of test compound which gave 50% inhibition of enzyme activity.
20. For review of bio-isostere replacement of functional groups see: C.G. Wermuth The Practice of Medicinal Chemistry 1996 Academic Press pp. 204-237
21. X. Chen, and W. Wang Ann. Rep. in Med. Chem. 38 2003 333
22. A. Basha, M. Lipton, and S.M. Weinreb Tetrahedron Lett. 18 1977 4174
23. A. Batch, and R.H. Dodd J. Org. Chem. 63 1998 872
24. A. Mehta, and R.H. Dodd J. Org. Chem. 58 1993 7587
25. Typical condition in Smith Synthesiser microwave was heating to 150 °C for 10 min in toluene solvent. More electron poor amines required prolonged times, for example 2-aminopyridine required 2 h.
26. In general ortho and para substituents resulted in at least a 20-fold drop in potency.
27. Five compounds are dosed as a cocktail (2 mg/kg each) with a QC compound (1 mg/kg) to 2 rats. Plasma samples, obtained at, 1, 2, 4 and 6 h post dose are analysed using a generic HPLC-MS procedure for the presence of parent compound.
28. P.J. Hajduk, and D.R. Sauer J. Med. Chem. 51 2008 553
29. A.G. Dossetter Bioorg. Med. Chem. 18 2010 4405
30. Jie-F; Vojkovsky, T.; Huang, P.; Liang, C.; Do, S.; Huy, S.; Koenig, M.; Cui, J. Preparation of triazolotriazines as c-Met modulators for treating cancer. PCT Int. Appl., WO2005/010005, 2005.
31. B.K. Albrecht, J.-C. Harmange, D. Bauer, L. Berry, C. Bode, A.A. Boezio, A. Chen, D. Choquette, I. Dussault, C. Fridrich, S. Hirai, D. Hoffman, J.F. Larrow, P. Kaplan-Lefko, J. Lin, J. Lohman, A.M. Long, J. Moriguchi, A. O'Connor, M.H. Potashman, M. Reese, K. Rex, A. Siegmund, K. Shah, R. Shimanovich, S.K. Springer, Y. Teffera, Y. Yang, Y. Zhang, and S.F. Bellon J. Med. Chem. 51 2008 2879
32. J. Porter, S. Lumb, F. Lecomte, J. Reuberson, A. Foley, M. Calmiano, K. le Riche, H. Edwards, J. Delgado, R.J. Franklin, J.M. Gascon-Simorte, A. Maloney, C. Meier, and M. Batchelor Bioorg. Med. Chem. Lett. 19 2009 397
33. For more detailed description of the molecular modelling see Supplementary data.
34. W. Wang, A. Marimuthu, J. Tsai, A. Kumar, H.I. Krupka, C. Zhang, B. Powell, Y. Suzuki, H. Nguyen, M. Tabrizizad, C. Luu, and B.L. West PNAS 103 2006 3563