Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 21, 2011, Pages 6366-6369

  Nishiguchi, Gisele A ^a   Atallah, Gordana ^a   Bellamacina, Cornelia ^a   Burger, Matthew T ^a   Ding, Yu ^a   Feucht, Paul H ^a   Garcia, Pablo D ^a   Han, Wooseok ^a   Klivansky, Liana ^a,b   Lindvall, Mika ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

Author keywords

Indole; Kinase selectivity; Oncology; Pim kinase inhibitors

Indexed keywords

3,5 DISUBSTITUTED INDOLE DERIVATIVE; INDOLE DERIVATIVE; PROTEIN KINASE; PROTEIN KINASE PIM 1; PROTEIN KINASE PIM 2; PROTEIN KINASE PIM 3; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DRUG DESIGN; HIGH THROUGHPUT SCREENING; PROTEIN STRUCTURE; STRUCTURE ACTIVITY RELATION;

EID: 80054787028     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.08.105     Document Type: Article

References (29)

1. Nawijin, M. C.; Alendar, A.; Berns, A. Nat. Rev. Cancer 2011, 11, 23
2. Brault, L.; Gasser, C.; Bracher, F.; Huber, K.; Knapp, S.; Schwaller, J. Haematologica 2010, 95, 1004.
3. Qian, K. C.; Wang, L.; Hickey, E. R.; Studts, J.; Barringer, K.; Peng, C.; Kronkaitis, A.; Li, J.; White, A.; Mische, S.; Farmer, B. J. Biol. Chem. 2005, 280, 6130
4. Bullock, A. N.; Debreczeni, J.; Amos, A. L.; Knapp, S.; Turk, B. E. J. Biol. Chem. 2005, 280, 41675.
5. Mikkers, H.; Nawijn, M.; Allen, J.; Brouwers, C.; Verhoeven, E.; Jonkers, J.; Berns, A. Mol. Cell. Biol. 2004, 24, 6104.
6. Amson, R.; Sigaux, F.; Przedborski, S.; Flandrin, G.; Givol, D.; Telerman, A. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 8857
7. Warnecke-Eberz, U.; Bollschweiler, E.; Drebber, U.; Metzger, R.; Baldus, S.; Holscher, A. H.; Monig, S. Anticancer Res. 2009, 29(11), 4451
8. Mumenthaler, S. M.; Ng, P. Y.; Hodge, A.; Bearss, D.; Berk, G.; Kanekal, S.; Redkar, S.; Taverna, P.; Agus, D. B.; Jain, A. Mol. Cancer Ther. 2009, 8(10), 2882.
9. Cohen, A. M.; Grinblat, B.; Bessler, H.; Kristt, D. A.; Kremer, A.; Shalom, S.; Schwartz, A.; Halperin, M.; Merkel, D.; Don, J. Leuk. Lymphoma 2004, 45, 951
10. Breuer, M. L.; Cuypers, H. T.; Berns, A. EMBO J. 1989, 8, 743.
11. Zheng, H. C.; Tsuneyama, K.; Takahashi, H.; Miwa, S.; Sugiyama, T.; Popivanova, B. K.; Fujii, C.; Nomoto, K.; Mukaida, N.; Takano, Y. J. Cancer Res. Clin. Oncol. 2008, 134, 481
12. Li, Y.; Popivanova, B. K.; Nagai, Y.; Ishikura, H.; Fujii, C.; Mukaida, N. Cancer Res. 2006, 66, 6741.
13. Morishita, D.; Katayama, R.; Sekimizu, K.; Tsuruo, T.; Fujita, N. Cancer Res. 2008, 68, 5076
14. Gong, J.; Wang, J.; Ren, K.; Liu, C.; Li, B.; Shi, Y. J. Surg. Res. 2009, 153, 17.
15. Amaravadi, R.; Thompson, C. B. J. Clin. Invest. 2005, 115, 2618.
16. Morwick, T. Expert Opin. Ther. Patents 2010, 20, 193
17. The Pim1 complexed structure of 2.6 Ang and 99% complete has been deposited into the RSCB as PBD ID 3T9I. The final R and R-Free values were 0.165 and 0.227, respectively. Additional information can be found in the header file of the submitted pdb file.
18. Jacobs, M. D.; Black, J.; Futer, O.; Swenson, L.; Hare, B.; Fleming, M.; Saxena, K. J. Biol. Chem. 2005, 280, 13728
19. Qian, K. C.; Wang, L.; Hickey, E. R.; Studts, J.; Barringer, K.; Peng, C.; Kronkaitis, A.; Li, J.; White, A.; Mische, S.; Farmer, B. J. Biol. Chem. 2005, 280, 6130
20. Kumar, A.; Mandiyan, V.; Suzuki, Y.; Zhang, C.; Rice, J.; Tsai, J.; Artis, D. R.; Ibrahim, P.; Bremer, R. J. Mol. Biol. 2005, 348, 183.
21. See Supplementary data.
22. Arora, N.; Billedeau, R. J.; Dewdney, N. J.; Gabriel, T.; Goldstein, D. M.; Soth, M.; Trejo-Martin, T. A. WO 2005 085248A1.
23. Results not shown.
24. Tao, Z.; Hasvold, L. A.; Leverson, J. D.; Han, E. K.; Guan, R.; Johnson, E. F.; Stoll, V. S.; Steward, K. D.; Stamper, G.; Soni, N.; Bouska, J. J.; Luo, Y.; Sowin, T. J.; Lin, N.; Giranda, V. S.; Rosenberg, S. H.; Penning, T. D. J. Med. Chem. 2009, 52, 6621
25. Grey, R.; Pierce, A. C.; Bemis, G. W.; Jacobs, M. D.; Moody, C. S.; Jajoo, R.; Mohal, N.; Green, J. Bioorg. Med. Chem. Lett. 2009, 19, 3019
26. Qian, K.; Wang, L.; Cywin, C. L.; Farmer, B. T.; Hickey, E.; Homon, C.; Jakes, S.; Kashem, M. A.; Lee, G.; Leonard, S.; Li, J.; Magboo, R.; Mao, W.; Pack, E.; Peng, C.; Prokopowicz, A.; Welzel, M.; Wolak, J.; Morwick, T. J. Med. Chem. 2009, 52, 1814
27. Tong, Y.; Stewart, K. D.; Thomas, S.; Przytulinska, M.; Johnson, E. F.; Klinghofer, V.; Leverson, J.; McCall, O.; Soni, N. B.; Luo, Y.; Lin, N.; Sowin, T. J.; Giranda, V. L.; Penning, T. D. Bioorg. Med. Chem. Lett. 2008, 18, 5206
28. Pierce, A. C.; Jacobs, M.; Stuver-Moody, C. J. Med. Chem. 2008, 51, 1972.
29. Studies to be reported in a separate communication.