N3-Arylmalonamides: A new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 24, 2009, Pages 6836-6839

  Saavedra, Oscar ^a   Claridge, Stephen ^a   Zhan, Lijie ^a   Raeppel, Franck ^a   Granger, Marie Claude ^a   Raeppel, Stéphane ^a   Mannion, Michael ^a   Gaudette, Frédéric ^a   Zhou, Nancy ^a   Isakovic, Ljubomir ^a   Bernstein, Naomy ^a   Déziel, Robert ^a   Nguyen, Hannah ^a   Beaulieu, Normand ^a   Beaulieu, Carole ^a   Dupont, Isabelle ^a   Wang, James ^a   Macleod, A Robert ^a   Besterman, Jeffrey M ^a   Vaisburg, Arkadii ^a  

^a Department of Medicinal Chemistry ^*  (Canada)

Author keywords

c Met; Oncology; RTK inhibitors; Thieno 3,2 b pyridine scaffold; VEGFR2

Indexed keywords

PYRIDINE DERIVATIVE; SCATTER FACTOR RECEPTOR; SORAFENIB; SUNITINIB; THIENO[3,2 B]PYRIDINE; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2; ANTINEOPLASTIC AGENT; MALONAMIDE; MALONIC ACID DERIVATIVE; PROTEIN KINASE INHIBITOR; THIENOPYRIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG DESIGN; DRUG STRUCTURE; ENZYME INHIBITION; GLIOBLASTOMA; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LUNG TUMOR; MOUSE; NONHUMAN; STOMACH TUMOR; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; ORAL DRUG ADMINISTRATION; SYNTHESIS; TUMOR CELL LINE;

MUS;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; HUMANS; MALONATES; MICE; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET; PYRIDINES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 71849092561     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.10.095     Document Type: Article

References (37)

1. Cohen P. Nat. Rev. Drug Disc. 1 (2002) 243
2. Blume-Jensen P., and Hunter T. Nature (2001) 355
3. Sartore-Bianchi A., Ricotta R., Cerea G., Maugeri M.R., and Siena S. Int. J. Biol. Markers 22 (2007) S77
4. Arora A., and Scholar E.M. J. Pharmacol. Exp. Ther. 315 (2005) 971
5. Garcia-Echeverria C., and Fabbro D. Mini-Rev. Med. Chem. 4 (2004) 273
6. Chouhan J.D., Zamarripa D.E., Lai P.H., Oramasionwu C.U., and Grabinski J.L. J. Oncol. Pharm. Pract. 13 (2007) 5
7. Wilhelm S., Carter C., Lynch M., Lowinger T., Dumas J., Smith R.A., Schwartz B., Simantov R., and Kelley S. Nat. Rev. Drug Disc. 5 (2006) 835
8. Ferrara N., Gerber H.P., and LeCouter J. Nat. Med. 9 (2003) 669
9. Dumas J., and Dixon J.A. Expert Opin. Ther. Patents 15 (2005) 647
10. Paz K., and Zhu Z. Front. Biosci. 10 (2005) 1415
11. Loriot Y., Massard C., and Armand J.-P. Oncologie 8 (2006) 815
12. Morabito A., De Maio E., Di Maio M., Normanno N., and Perrone F. The Oncologist 11 (2007) 753
13. Kiselyov A.S., Balakin K., and Tkachenko S.E. Expert Opin. Invest. Drugs 16 (2007) 83
14. Schenone S., Bondavalli F., and Botta M. Curr. Med. Chem. 14 (2007) 2495
15. Zhong H., and Bowen J.P. Curr. Top. Med. Chem. 7 (2007) 1379
16. Underiner T.L., Ruggeri B., and Gingrich D.E. Curr. Med. Chem. 11 (2004) 731 plus the 10 first references in this review
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. Knudsen B.S., and Vande Woude G. Curr. Opin. Gen. Dev. 18 (2008) 87
25. 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
26. 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
27. 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
28. Toschi L., and Jänne P.A. Clin. Cancer Res. 14 (2008) 5941
29. 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
30. Saavedra, O.; Claridge, S.; Zhan, L.; Raeppel, F.; Vaisburg, A.; Raeppel, S.; Deziel, R.; Mannion, M.; Zhou, N.; Gaudette, F.; Isakovic, L.; Wahhab, A.; Granger, M.-C.; Bernstein, N. WO 2007/0004675 A1.
31. 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
32. Fujiwara, A.; Senga, T.; Nishitoba, T.; Osawa, T.; Miwa, A.; Nakamura, K. PCT Int. Patent Appl. WO 2003/000660.
33. Fujiwara, A.; Senga, T.; Nishitoba, T.; Osawa, T.; Miwa, A.; Nakamura, K. U.S. Patent 2004/0242603.
34. Bannen, L. C.; Chan, D. S.; Chen, J.; Dalrymple, L. E.; Forsyth, T. P.; Huynh, T. P.; Jammalamadaka, V.; Khoury, R. G.; Leahy, J. W.; Mac, M. B.; Mann, G.; Mann, L. W.; Nuss, J. M.; Parks, J. J.; Takeuchi, C. S.; Wang, Y.; Xu, W. PCT Int. Patent Appl. WO 2005/030140.
35. Compound 21 at a concentration of 100 nM inhibited the following enzymes: Flt-3 (100%), Tie-2 (100%), PDGFRα (99%), c-Kit (99%), VEGFR1 (98%), VEGFR3 (97%), Aurora A (96%), EphB4 (95%), c-SRC (93%). Compound 21 had <5% inhibitory activity against the following enzymes CDK2/Cyclin E, EGFR, GSK3β, IKKβ, PKBα. Compound 21 was evaluated using the Kinaseprofiler™ Kinase Selectivity Screening Service (radiometric protein kinase assays) by Millipore.
36. 50s were calculated in a four parameters equation curve plotting inhibition (%).
37. 50 curves using a 4-parameter fit model. These curves were calculated using grafit 5.0 software.