The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 21, 2005, Pages 4666-4670

  Graczyk, Piotr P ^a   Khan, Afzal ^a   Bhatia, Gurpreet S ^a   Palmer, Vanessa ^a   Medland, Darren ^a   Numata, Hirotoshi ^a   Oinuma, Hitoshi ^a   Catchick, Jacqueline ^a   Dunne, Angela ^a   Ellis, Moira ^a   Smales, Caroline ^a   Whitfield, Jonathan ^a   Neame, Stephen J ^a   Shah, Bina ^a   Wilton, Daniel ^a   Morgan, Louise ^a   Patel, Toshal ^a   Chung, Raymond ^a   Desmond, Howard ^a   Staddon, James M ^a   Sato, Nobuaki ^b   Inoue, Atsushi ^b   more..

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b EISAI CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

IMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; POTASSIUM ION; SB 227931; STRESS ACTIVATED PROTEIN KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BRAIN NERVE CELL; CEREBELLUM; CORRELATION ANALYSIS; DRUG POTENCY; DRUG SYNTHESIS; ENANTIOMER; ENZYME PHOSPHORYLATION; IC 50; NERVE CELL NECROSIS; NEUROPROTECTION; NONHUMAN; RAT;

ANIMALS; CELL DEATH; CEREBELLUM; IMIDAZOLES; MITOGEN-ACTIVATED PROTEIN KINASE 10; NEURONS; NEUROPROTECTIVE AGENTS; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-JUN; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 25144508949     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.07.076     Document Type: Article

References (40)

1. M.P. Mattson, J. Partin, and J.G. Begley Brain Res. 807 1998 167
2. M. Barinaga Science 281 1998 1303
3. D.L. McPhie, R. Coopersmith, A. Hines-Peralta, Y. Chen, K.J. Ivins, S.P. Manly, M.R. Kozlowski, K.A. Neve, and R.L. Neve J. Neurosci. 23 2003 6914
4. T. Katayama, K. Imaizumi, T. Manabe, J. Hitomi, T. Kudo, and M. Tohyama J. Chem. Neuroanat. 28 2004 67
5. C.A. Gutekunst, F. Norflus, and S.M. Hersch Curr. Opin. Neurol. 13 2000 445
6. M.A. Hickey, and M.-F. Chesselet Prog. Neuro-psychoph. 27 2003 255
7. A. Hartley, J.M. Stone, C. Heron, J.M. Cooper, and A.H. Schapira J. Neurochem. 63 1994 1987
8. I. Ziv, E. Melamed, N. Nardi, D. Luria, A. Achiron, D. Offen, and A. Barzilai Neurosci. Lett. 170 1994 136
9. I. Vermes, E.N. Steur, G.F. Jirikowski, and C. Haanen Movement Disord. 19 2004 1252
10. S. Rabizadeh, E.B. Gralla, D.R. Borchelt, R. Gwinn, J.S. Valentine, S. Sisodia, P. Wong, M. Lee, H. Hahn, and D.E. Bredesen Proc. Natl. Acad. Sci. U.S.A. 92 1995 3024
11. A. Ferri, M. Nencini, A. Casciati, M. Cozzolino, D.F. Angelini, P. Longone, A. Spalloni, G. Rotilio, and M.T. Carri FASEB J. 18 2004 1261
12. P. Graczyk Prog. Med. Chem. 39 2002 1
13. M. Vila, and S. Przedborski Nat. Rev. Neurosci. 4 2003 1
14. P.C. Waldmeier, and W.G. Tatton Drug Discovery Today 9 2004 210
15. S. Lund, P. Porzgen, A.L. Mortensen, H. Hasseldam, D. Bozyczko-Coyne, S. Morath, T. Hartung, M. Bianchi, P. Ghezzi, M. Bsibsi, S. Dijkstra, and M. Leist J. Neurochem. 92 2005 1439
16. D. Bozyczko-Coyne, M.S. Saporito, and R.L. Hudkins Curr. Drug Targets: CNS Neurol. Disord. 1 2002 31
17. A.M. Manning, and R.J. Davis Nat. Rev. Drug Disc. 2 2003 554
18. Y. Gao, A.P. Signore, W. Yin, G. Cao, X.M. Yin, F. Sun, Y. Luo, S.H. Graham, and J. Chen J. Cerebr. Blood F. Met. 2005 1
19. Q.H. Guan, D.S. Pei, Q.G. Zhang, Z.B. Hao, T.L. Xu, and G.Y. Zhang Brain Res. 1035 2005 51
20. T. Borsello, P.G. Clarke, L. Hirt, A. Vercelli, M. Repici, D.F. Schorderet, J. Bogousslavsky, and C. Bonny Nat. Med. 9 2003 1180
21. Clinical trial has been discontinued (Cephalon press release on 11 May, 2005).
22. A.A. Mohit, J.H. Martin, and C.A. Miller Neuron 14 1995 67
23. D.D. Yang, C.-Y. Kuan, A.J. Whitmarsh, M. Rincon, T.S. Zheng, R.J. Davis, P. Rakic, and R.A. Flavell Nature 389 1997 865
24. C.-Y. Kuan, A.J. Whitmarsh, D.D. Yang, G. Liao, A.J. Schloemer, C. Dong, J. Bao, K.J. Banasiak, G.G. Haddad, R.A. Flavell, R.J. Davis, and P. Rakic Proc. Natl. Acad. Sci. U.S.A. 100 2003 15184
25. S. Hunot, M. Vila, P. Teismann, R.J. Davis, E.C. Hirsch, S. Przedborski, P. Rakic, and R.A. Flavell Proc. Natl. Acad. Sci. U.S.A. 101 2004 665
26. A. Behrens, M. Sibilia, and E.F. Wagner Nat. Genet. 21 1999 326
27. J.M. Lisnock, P. Griffin, J. Calaycay, B. Frantz, J. Parsons, S.J. O'Keefe, and P. LoGrasso Biochemistry 39 2000 3141
28. P.R. Young, M.M. McLaughlin, S. Kumar, S. Kassis, M.L. Doyle, D. McNulty, T.F. Gallagher, S. Fisher, P.C. McDonnell, S.A. Carr, M.J. Huddleston, G. Seibel, T.G. Porter, G.P. Livi, J.L. Adams, and J.C. Lee J. Biol. Chem. 272 1997 12116
29. V.Y. Bolshakov, L. Carboni, M.H. Cobb, S.A. Siegelbaum, and F. Belardetti Nat. Neurosci. 3 2000 1107
30. Z. Guan, J.H. Kim, S. Lomvardas, K. Holick, S. Xu, E.R. Kandel, and J.H. Schwartz J. Neurosci. 23 2003 7317
31. U. Leutenegger, G. Umbricht, C. Fahrni, P. von Matt, and A. Pfaltz Tetrahedron 48 1992 2143
32. L.C. King, and G.K. Ostrum J. Org. Chem. 29 1964 3459
33. 5O, 368.1887 (M+1); found: 368.1874.
34. G. Scapin, S. Patel, J. Lisnock, J. Becker, and P. LoGrasso Chem. Biol. 10 2003 705 Structure: 1PMN
35. J. Cao, M.M. Semenova, V.T. Solovyan, J. Han, E.T. Coffey, and M.J. Courtney J. Biol. Chem. 279 2004 35903
36. 23 Neurons were cultured for 7 days in basal modified Eagle's medium containing 2 mM l-glutamine, 25 mM KCl, 35 mM glucose, and 10% foetal bovine serum.
37. A. Eilers, J. Whitfield, C. Babij, L.L. Rubin, and J. Ham J. Neurosci. 18 1998 1713
38. Due to very high homology between JNK isoforms inhibitors 3-5, were expected to inhibit c-Jun phosphorylation, regardless of the isoform.
39. T. Mosmann J. Immunol. Methods 65 1983 55
40. A.O. da Costa, M.C. de Assis, A. Marques Ede, and M.C. Plotkowski Biocell 23 1999 65