N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 23, 2009, Pages 6552-6556

  Mannion, Michael ^a   Raeppel, Stéphane ^a   Claridge, Stephen ^a   Zhou, Nancy ^a   Saavedra, Oscar ^a   Isakovic, Ljubomir ^a   Zhan, Lijie ^a   Gaudette, Frédéric ^a   Raeppel, Franck ^a   Déziel, Robert ^a   Beaulieu, Normand ^a   Nguyen, Hannah ^a   Chute, Ian ^a   Beaulieu, Carole ^a   Dupont, Isabelle ^a   Robert, Marie France ^a   Lefebvre, Sylvain ^a   Dubay, Marja ^a   Rahil, Jubrail ^a   Wang, James ^a   Ste Croix, Hélène ^a   Robert Macleod, A ^a   Besterman, Jeffrey M ^a   Vaisburg, Arkadii ^a   more..

^a METHYLGENE INC   (Canada)

Author keywords

c Met; Oncology; Quinoline scaffold; RTK inhibitors; VEGFR2

Indexed keywords

AMIDE; N (4 (6,7 DISUBSTITUTED QUINOLIN 4 YLOXY) 3 FLUOROPHENYL) 2 OXO 3 PHENYLIMIDAZOLIDINE 1 CARBOXAMIDE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SCATTER FACTOR RECEPTOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2;

ANIMAL MODEL; ARTICLE; DRUG EFFICACY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; RAT; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; RECEPTOR PROTEIN-TYROSINE KINASES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS;

EID: 71749102468     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.10.040     Document Type: Article

References (58)

1. Blume-Jensen P., and Hunter T. Nature 411 (2001) 355
2. Ma P.C., Maulik G., Christensen J., and Salgia R. Cancer Metastasis Rev. 22 (2003) 309
3. Birchmeier C., Birchmeier W., Gherardi E., and Vande Woude G.F. Nat. Rev. Mol. Cell Biol. 4 (2003) 915
4. Christensen J.G., Burrows J., and Salgia R. Cancer Lett. 225 (2005) 1
5. Corso S., Comoglio P.M., and Giordano S. Trends Mol. Med. 11 (2005) 284
6. Boccaccio C., and Comoglio P.M. Nat. Rev. Cancer 6 (2006) 637
7. Peruzzi B., and Bottaro D.P. Clin. Cancer Res. 12 (2006) 3657
8. Knudsen B.S., and Vande Woude G. Curr. Opin. Gen. Dev. 18 (2008) 87
9. Toschi L., and Jänne P.A. Clin. Cancer Res. 14 (2008) 5941
10. Dussault I., and Bellon S.F. Anti-Cancer Agents Med. Chem. 9 (2009) 221
11. Cipriani N.A., Abidoye O.O., Vokes E., and Salgia R. Lung Cancer 63 (2009) 169
12. Ferrara N., Gerber H.P., and LeCouter J. Nat. Med. 9 (2003) 669
13. Paz K., and Zhu Z. Front. Biosci. 10 (2005) 1415
14. Cui J. Expert Opin. Ther. Patents 16 (2006) 713
15. Cui J.J. Expert Opin. Ther. Patents 17 (2007) 1035
16. Abidoye O., Murukurthy N., and Salgia R. Rev. Recent Clin. Trials 2 (2007) 143
17. Zou H.Y., Li Q., Lee J.H., Arango M.E., McDonnell S.R., Yamazaki S., Koudriakova T.B., Alton G., Cui J.J., Kung P.-P., Nambu M.D., Los G., Bender S.L., Mroczkowski B., and Christensen J.G. Cancer Res. 67 (2007) 4408
18. Kung P.-P., Funk L., Meng J., Alton G., Padrique E., and Mroczkowski B. Eur. J. Med. Chem. 43 (2008) 1321
19. Bellon S.F., Kaplan-Lefko P., Yang Y., Zhang Y., Moriguchi J., Rex K., Johnson C.W., Rose P.E., Long A.M., O'Connor A.B., Gu Y., Coxon A., Kim T.-S., Tasker A., Burgess T.L., and Dussault I. J. Biol. Chem. 283 (2008) 2675
20. Schroeder G.M., Chen X.-T., Williams D.K., Nirschl D.S., Cai Z.-W., Wei D., Tokarski J.S., An Y., Sack J., Chen Z., Huynh T., Vaccaro W., Poss M., Wautlet B., Gullo-Brown J., Kellar K., Manne V., Hunt J.T., Wong T.W., Lombardo L.J., Fargnoli J., and Borzilleri R.M. Bioorg. Med. Chem. Lett. 18 (2008) 1945
21. Cai Z.-W., Wei D., Schroeder G.M., Cornelius L.A.M., Kim K., Chen X.-T., Schmidt R.J., Williams D.K., Tokarski J.S., An Y., Sack J., Manne V., Kamath A., Zhang Y., Marathe P., Hunt J.T., Lombardo L.J., Fargnoli J., and Borzilleri R.M. Bioorg. Med. Chem. Lett. 18 (2008) 3224
22. Albrecht B.K., Harmange J.-C., Bauer D., Berry L., Bode C., Boezio A.A., Chen A., Choquette D., Dussault I., Fridrich C., Hirai S., Hoffman D., Larrow J.F., Kaplan-Lefko P., Lin J., Lohman J., Long A.M., Moriguchi J., O'Connor A., Potashman M.H., Reese M., Rex K., Siegmund A., Shah K., Shimanovich R., Springer S.K., Teffera Y., Yang Y., Zhang Y., and Bellon S.F. J. Med. Chem. 51 (2008) 2879
23. Comoglio P.M., Giordano S., and Trusolino L. Nat. Rev. Drug Disc. 7 (2008) 504
24. Liu L., Siegmund A., Xi N., Kaplan-Lefko P., Rex K., Chen A., Lin J., Moriguchi J., Berry L., Huang L., Teffera Y., Yang Y., Zhang Y., Bellon S.F., Lee M., Shimanovich R., Bak A., Dominguez C., Norman M.H., Harmange J.-C., Dussault I., and Kim T.-S. J. Med. Chem. 51 (2008) 3688
25. Kim K.S., Zhang L., Schmidt R., Cai Z.-W., Wei D., Williams D.K., Lombardo L.J., Trainor G.L., Xie D., Zhang Y., An Y., Sack J.S., Tokarski J.S., Darienzo C., Kamath A., Marathe P., Zhang Y., Lippy J., Jeyaseelan Sr. R., Wautlet B., Henley B., Gullo-Brown J., Manne V., Hunt J.T., Fargnoli J., and Borzilleri R.M. J. Med. Chem. 51 (2008) 5330
26. D'Angelo N.D., Bellon S.F., Booker S.K., Cheng Y., Coxon A., Dominguez C., Fellows I., Hoffman D., Hungate R., Kaplan-Lefko P., Lee M.R., Li C., Liu L., Rainbeau E., Reider P.J., Rex K., Siegmund A., Sun Y., Tasker A.S., Xi N., Xu S., Yang Y., Zhang Y., Burgess T.L., Dussault I., and Kim T.-S. J. Med. Chem. 51 (2008) 5766
27. Schroeder G.M., An Y., Cai Z.-W., Chen X.-T., Clark C., Cornelius L.A.M., Dai J., Gullo-Brown J., Gupta A., Henley B., Hunt J.T., Jeyaseelan R., Kamath A., Kim K., Lippy J., Lombardo L.J., Manne V., Oppenheimer S., Sack J., Schmidt R.J., Shen G., Stefanski K., Tokarski J.S., Trainor G.L., Wautlet B.S., Wei D., Williams D.K., Zhang Y., Zhang Y., Fargnoli J., and Borzilleri R. J. Med. Chem. 52 (2009) 1251
28. Porter J., Lumb S., Lecomte F., Reuberson J., Foley A., Calmiano M., Le Riche K., Edwards H., Delgado J., Franklin R.J., Gascon-Simorte J.M., Maloney A., Meier C., and Batchelor M. Bioorg. Med. Chem. Lett. 19 (2009) 397
29. Koolman H., Heinrich T., Böttcher H., Rautenberg W., and Reggelin M. Bioorg. Med. Chem. Lett. 19 (2009) 1879
30. Porter J., Lumb S., Franklin R.J., Gascon-Simorte J.M., Calmiano M., Riche L.K., Lallemand B., Keyaerts J., Edwards H., Maloney A., Delgado J., King L., Foley A., Lecomte F., Reuberson J., Meier C., and Batchelor M. Bioorg. Med. Chem. Lett. 19 (2009) 2780
31. Underiner T.L., Ruggeri B., and Gingrich D.E. Curr. Med. Chem. 11 (2004) 731
32. Dumas J., and Dixon J.A. Expert Opin. Ther. Patents 15 (2005) 647
33. Loriot Y., Massard C., and Armand J.-P. Oncologie 8 (2006) 815
34. Morabito A., De Maio E., Di Maio M., Normanno N., and Perrone F. Oncologist 11 (2007) 753
35. Kiselyov A.S., Balakin K., and Tkachenko S.E. Expert Opin. Invest. Drugs 16 (2007) 83
36. Cabebe E., and Fisher G.A. Expert Opin. Invest. Drugs 16 (2007) 467
37. Zhong H., and Bowen J.P. Curr. Top. Med. Chem. 7 (2007) 1379
38. Schenone S., Bondavalli F., and Botta M. Curr. Med. Chem. 14 (2007) 2495
39. Bilanges B., Torbett N., and Vanhaesebroeck B. Nat. Chem. Biol. 4 (2008) 648
40. WO 2001/60814 A2.
41. WO 2002/096361 A2.
42. Faivre S., Delbaldo C., Vera K., Robert C., Lozahic S., Lassau N., Bello C., Deprimo S., Brega N., Massimini G., Armand J.P., Scigalla P., and Raymond E. J. Clin. Oncol. 24 (2006) 25
43. Faivre S., Demetri G., Sargent W., and Raymond E. Nat. Rev. Drug Disc. 6 (2007) 734
44. Christensen J.G., Schreck R., Burrows J., Kuruganti P., Chan E., Le P., Chen J., Wang X., Ruslim L., Blake R., Lipson K.E., Ramphal J., Do S., Cui J.J., Cherrington J.M., and Mendel D.B. Cancer Res. 63 (2003) 7345
45. Ma P.C., Schaefer E., Christensen J.G., and Salgia R. Clin. Cancer Res. 11 (2005) 2312
46. Smolen G.A., Sordella R., Muir B., Mohapatra G., Barmettler A., Archibald H., Kim W.J., Okimoto R.A., Bell D.W., Sgroi D.C., Christensen J.G., Settleman J., and Haber D.A. Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 2316
47. WO 2003/000660 A1.
48. WO 2005/030140 A2.
49. Claridge S., Raeppel F., Granger M.-C., Bernstein N., Saavedra O., Zhan L., Llewellyn D., Wahhab A., Deziel R., Rahil J., Beaulieu N., Nguyen H., Dupont I., Barsalou A., Beaulieu C., Chute I., Gravel S., Robert M.-F., Lefebvre S., Dubay M., Pascal R., Gillespie J., Jin Z., Wang J., Besterman J., Macleod A.R., and Vaisburg A. Bioorg. Med. Chem. Lett. 18 (2008) 2793
50. Raeppel S., Claridge S., Saavedra O., Gaudette F., Zhan L., Mannion M., Zhou N., Raeppel F., Granger M.-C., Isakovic L., Déziel R., Nguyen H., Beaulieu N., Beaulieu C., Dupont I., Robert M.-F., Lefebvre S., Dubay M., Rahil J., Wang J., Ste-Croix H., Macleod A.R., Besterman J., and Vaisburg A. Bioorg. Med. Chem. Lett. 19 (2009) 1323
51. The details for the synthesis and the characterization of all the new compounds are described in U.S. 2008/0004273 A1.
52. Patent application from Bayer AG, Chem. Abstr. 1975, 84, 4975.
53. Maclaren J.A. Aust. J. Chem. 30 (1977) 455
54. Su W., and Zhang Y. J. Chem. Res. Synop. 9 (2000) 440
55. Mayer P., Brunel P., Chaplain C., Piedecoq C., Calmel F., Schambel P., Chopin P., Wurch T., Pauwels P.J., Marien M., Vidaluc J.-L., and Imbert T. J. Med. Chem. 43 (2000) 3653
56. 50s were calculated in a four parameters equation curve plotting inhibition (%).
57. 50 curves using a four-parameter fit model. These curves were calculated using GraFit 5.0 software.
58. Compounds 25-27 caused cell vacuolation and precipitated during the Phospho-TPR-Met and the HGF-induced epithelial cell migration and scattering cell-based assays.