6382
R. Jiang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 6378–6382
10. Zhang, H.; Shi, X.; Zhang, Q.-J.; Hampong, M.; Paddon,
H.; Wahyuningsih, D.; Pelech, S. J. Biol. Chem. 2002, 277,
43648.
19. Stocks, M. J.; Barber, S.; Ford, R.; Leroux, F.; St-Gally,
S.; Teague, S.; Xue, Y. Bioorg. Med. Chem. Lett. 2005, 15,
3459.
11. Kyriakis, J. M.; Avruch, J. Physiol. Rev. 2001, 81, 807.
12. Zhang, G.-Y.; Zhang, Q.-G. Expert Opin. Invest. Drugs
2005, 14, 1373.
20. Swahn, B.-M.; Xue, Y.; Arzel, E.; Kallin, E.; Magnus, A.;
Plobeck, N.; Viklund, J. Bioorg. Med. Chem. Lett. 2006,
16, 1397.
13. Kuan, C.-Y.; Whitmarsh, A. J.; Yang, D. D.; Liao, G.;
Schloemer, A. J.; Davis, R. J.; Rakic, P. Proc. Natl. Acad.
Sci. U.S.A. 2003, 100, 15184.
14. Bennett, B. L.; Sasaki, D. T.; Murray, B. W.; O’Leary, E.
C.; Sakata, S. T.; Xu, W.; Leisten, J. C.; Motiwala, A.;
Pierce, S.; Satoh, Y.; Bhagwat, S. S.; Manning, A. M.;
Anderson, D. W. Proc. Natl. Acad. Sci. U.S.A. 2001, 98,
13681.
21. For the review of reported JNK inhibitors, see: Szcze-
pankiewicz, B. G.; Kosogof, C.; Nelson, L. T. J.; Liu, G.;
Liu, B.; Zhao, H.; Serby, M. D.; Xin, Z.; Liu, M.; Gum,
R. J.; Haasch, D. L.; Wang, S.; Clampit, J. E.; Johnson, E.
F.; Lubben, T. H.; Stashko, M. A.; Olejniczak, E. T.; Sun,
C.; Dorwin, S. A.; Haskins, K.; Abad-Zapatero, C.; Fry,
E. H.; Hutchins, C. W.; Sham, H. L.; Rondinone, C. M.;
Trevillyan, J. M. J. Med. Chem. 2006, 49, 3563.
15. Ruckle, T.; Biamonte, M.; Grippi-Vallotton, T.; Arkin-
stall, S.; Cambet, Y.; Camps, M.; Chabert, C.; Church, D.
J.; Halazy, S.; Jiang, X.; Martinou, I.; Nichols, A.; Sauer,
W.; Gotteland, J.-P. J. Med. Chem. 2004, 47, 6921.
16. Graczyk, P. P.; Khan, A.; Bhatia, G. S.; Palmer, V.;
Medland, D.; Numata, H.; Oinuma, H.; Catchich, J.;
Dunne, A.; Ellis, M.; Smales, C.; Whitfield, J.; Neame, S.
J.; Shah, B.; Wilton, D.; Morgan, L.; Patel, T.; Chung, R.;
Desmond, H.; Staddon, J. M.; Sato, N.; Inoue, A. Bioorg.
Med. Chem. Lett. 2005, 15, 4666.
17. Gaillard, P.; Jeanclaude-Etter, I.; Ardissone, V.; Arkinstall,
S.; Cambet, Y.; Camps, M.; Chaber, C.; Church, D.; Cirillo,
R. A.; Gotteland, J.-P. J. Med. Chem. 2005, 48, 4596.
18. Swahn, B.-M.; Huerta, F.; Kallin, E.; Malmstrom, J.;
Weigelt, T.; Viklund, J.; Womack, P.; Xue, Y.; Phverg, L.
Bioorg. Med. Chem. Lett. 2005, 15, 5095.
22. Scapin, G.; Patel, S. B.; Lisnock, J.; Becker, J. W.;
LoGrasso, P. V. Chem. Biol. 2003, 10, 705.
23. Removal of N-2 on the C-ring of phenanthroline (1)
completely abolishes the inhibitory activity against JNK3.
24. Biochemical IC50s for JNK3 and p38 were determined
using HTRF. Briefly, final assay concentrations of JNK3,
biotinylated-ATF2 and ATP were 0.3 nM, 0.4 nM, and
1 lM, respectively. Final assay concentrations of p38,
biotinylated-ATF2, and ATP were 1 nM, 0.4 nM, and
11.5 lM, respectively. In both assays, the phosphor-
Thr71-ATF-2 product was detected by a Europium-
cryptate-labeled anti-phospho-Thr71-ATF-2 antibody.
Streptavidin–allophycocyanin–XL was used as the accep-
tor. A 10-point dose–response curve for each compound
was generated in duplicate and data were fit to a four-
parameter logistic.