Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2- ones as novel checkpoint 1 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 2, 2006, Pages 421-426

  Lin, Nan Horng ^a   Xia, Ping ^a   Kovar, Peter ^a   Park, Chang ^a   Chen, Zehan ^a   Zhang, Haiying ^a   Rosenberg, Saul H ^a   Sham, Hing L ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Checkpoint 1; Inhibitor; Kinase

Indexed keywords

3 ETHYLIDENE 1,3 DIHYDROINDOL 2 ONE DERIVATIVE; ANTINEOPLASTIC AGENT; CHECKPOINT KINASE 1; CHECKPOINT KINASE 1 INHIBITOR; DOXORUBICIN; ENZYME INHIBITOR; INDOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE G2 PHASE; CONTROLLED STUDY; DNA DAMAGE; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; HELA CELL; HUMAN; HUMAN CELL; IN VITRO STUDY;

CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HELA CELLS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 27944448722     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.09.064     Document Type: Article

References (35)

1. N.M. Martin J. Photochem. Photobiol. B 63 1-3 2001 162
2. C.D. Heinen, C. Schmutte, and R. Fishel Cancer Biol. Ther. 1 2002 477
3. D. Sampath, V.A. Rao, and W. Plunkett Oncogene 22 2003 9063
4. M.A. Ozbun, and J.S. Butel Adv. Cancer Res. 66 1995 71
5. J. Bartek, and J. Lukas Curr. Opin. Cell Biol. 13 2001 738
6. J. Bartek, and J. Lukas FEBS Lett. 490 2001 117
7. W.C. Hahn, and R.A. Weinberg Nat. Rev. Cancer 2 2002 331
8. D. Hanahan, and R.A. Weinberg Cell 100 2000 57
9. K.J. Russell, L.W. Wiens, G.W. Demers, D.A. Galloway, S.E. Plon, and M. Groudine Cancer Res. 55 1995 1639
10. S.N. Powell, J.S. DeFrank, P. Connell, M. Eogan, F. Preffer, D. Dombkowski, W. Tang, and S. Friend Cancer Res. 55 1995 1643
11. R.T. Bunch, and A. Eastman Cell Growth Differ. 8 1997 779
12. K. Koniaras, A.R. Cuddihy, H. Christopoulos, A. Hogg, and M.J. O'Connell Oncogene 20 2001 7453
13. E.A. Kohn, N.D. Ruth, M.K. Brown, M. Livingstone, and A.J. Eastman Biol. Chem. 277 2002 26553
14. E.A. Kohn, C.J. Yoo, and A. Eastman Cancer Res. 63 2003 31
15. A. Eastman, E.A. Kohn, M.K. Brown, J. Rathman, M. Livingstone, D.H. Blank, and G.W. Gribble Mol. Cancer Ther. 1 2002 1067
16. Q. Liu, S. Guntuku, X.-S. Cui, S. Matsuoka, D. Cortez, K. Tamai, G. Luo, S. Carattini-Rivera, F. DeMayo, A. Bradley, L.A. Donehower, and S.J. Elledge Gene Dev. 14 2000 1448
17. Y. Sanchez, C. Wong, R.S. Thoma, R. Richman, Z. Wu, H. Piwnica-Worms, and S.J. Elledge Science 277 1997 1497
18. C.Y. Peng, P.R. Graves, R.S. Thoma, Z. Wu, A.S. Shaw, and H. Piwnica-Worms Science 277 1997 1501
19. P.R. Graves, C.M. Lovly, G.L. Uy, and H. Piwnica-Worms Oncogene 20 2001 1839
20. Z. Xiao, Z. Chen, A.H. Gunasekera, T.J. Sowin, S.H. Rosenberg, S. Fesik, and H. Zhang J. Biol. Chem. 278 2003 21767
21. N. Mailand, J. Falck, C. Lukas, R.G. Syljuåsen, M. Welcker, J. Bartek, and J. Lukas Science 288 2000 1425
22. B.B. Zhou, and S.J. Elledge Nature 408 2000 433
23. W.A. Cliby, K.A. Lewis, K.K. Lilly, and S.H. Kaufmann J. Biol. Chem. 277 2002 1599
24. H. Zhao, J.L. Watkins, and H. Piwnica-Worms Proc. Nat. Acad. Sci. U.S.A. 99 2002 14795
25. J. Lukas, T. Herzinger, K. Hansen, M.C. Moroni, D. Resnitzky, K. Helin, S.I. Reed, and J. Bartek Gene Dev. 11 1997 1479
26. M. Suganuma Cancer Res. 59 23 1999 5887
27. Y. Luo Neoplasia (New York) 3 2001 411
28. H. Takai, K. Tominaga, N. Motoyama, Y.A. Minamishima, H. Nagahama, T. Tsukiyama, K. Ikeda, K. Nakayama, M. Nakanishi, and K. Nakayama Gene Dev. 14 2000 1439
29. J.R. Jackson, A. Gilmartin, C. Imburgia, J.D. Winkler, L.A. Marshall, and A. Roshak Cancer Res. 60 2000 566
30. Z. Chen, Z. Xiao, J. Chen, S.-C. Ng, T. Sowin, H. Sham, S. Rosenberg, S. Fesik, and H. Zhang Mol. Cancer Ther. 2 2003 543
31. Li G.; Li Q.; Li T.; Lin N-H.; Mantei R. A.; Sham H. L.; Wang G. T. US Patent Application 2004034038, 2004.
32. Keegan K.; Kesicki E. A.; Gaudino J. J.; Cook A. W.; Cowen S. D.; Gurgess, L. E. WO 02/070494, 2002.
33. Boyle R. G.; Imogai H. J.; Cherry M. WO 03/101444, 2003.
34. 33P were used in the assays. Compound vehicle DMSO was maintained at 2% in the final reaction. After 30 min at room temperature, the reaction was stopped by addition of an equal volume of 4 M NaCl and 0.1 M EDTA, pH 8. A 40 μL aliquot of the reaction was added to a well in a FlashPlate (NEN Life Science Products, Boston, MA) containing 160 μL of phosphate-buffered saline (PBS) without calcium chloride or magnesium chloride and incubated at room temperature for 10 min. The plate was then washed three times in PBS with 0.05% of Tween 20 and counted in a Packard TopCount counter (Packard BioScience Company, Meriden, CT).
35. The coordinates of the CHK1 complex have been deposited with the RCSB Protein Data Bank. The entry 'Crystal Structure of CHK1 with an Indole Inhibitor' has been assigned the RCSB ID code 'rcsb034461' and PDB ID code '2AYP'.