Indolin-2-one p38α inhibitors I: Design, profiling and crystallographic binding mode

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 14, 2011, Pages 4130-4133

  Eastwood, Paul ^a   González, Jacob ^a   Gómez, Elena ^a   Vidal, Bernat ^a   Caturla, Francisco ^a   Roca, Ramón ^a   Balagué, Cristina ^a   Orellana, Adelina ^a   Domínguez, María ^a  

^a Almirall SA ^*  (Spain)

Author keywords

Indolin 2 ones; Molecular modeling; p38 Inhibitors; Structure based design; X ray crystallography

Indexed keywords

INDOLIN 2 ONE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE 14 INHIBITOR; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG ELIMINATION; DRUG POTENCY; DRUG STRUCTURE; FEMALE; FIRST PASS EFFECT; HYDROGEN BOND; MOLECULAR MODEL; NONHUMAN; RAT; X RAY CRYSTALLOGRAPHY;

ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; INDOLES; MICROSOMES, LIVER; MITOGEN-ACTIVATED PROTEIN KINASE 14; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79959877983     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.05.114     Document Type: Article

References (29)

1. J. Han, J.D. Lee, L. Bibbs, and R.J. Ulevitch Science 265 1994 808
2. J. Raingeaud, S. Gupta, J.S. Rogers, M. Dickens, J. Han, R.J. Ulevitch, and R.J. Davis J. Biol. Chem. 271 1996 2886
3. J. Raingeaud, A.J. Whitmarsh, T. Barrett, B. Derijard, and R. Davis J. Mol. Cell. Biol. 16 1996 1247
4. A.M. Badger, J.N. Bradbeer, B. Votta, J.C. Lee, J.L. Adams, and D.E. Griswold J. Pharmacol. Exp. Ther. 279 1996 1453
5. M. Feldmann, F.M. Brennan, and R.N. Maini Annu. Rev. Immunol. 14 1996 397
6. P. Rutgeerts, G. D'Haens, S. Targan, E. Vasiliauskas, S.B. Hanauer, D.H. Present, L. Mayer, R.A. van Hogezand, T. Braakman, and K.L. DeWoody Gastroenterology 117 1999 761
7. M.L. Foster, F. Halley, and J.E. Souness Drug News Perspect. 13 2000 488
8. S. Kumar, J. Boehm, and J.C. Lee Nat. Rev. Drug Disc. 2 2003 717
9. J.C. Lee, J.T. Laydon, P.C. McDonnell, T.F. Gallagher, S. Kumar, D. Green, D. McNulty, M.J. Blumenthal, J.R. Heyes, S.W. Landvatter, J.E. Strickler, M.M. McLaughlin, I.R. Siemens, S.M. Fisher, G.P. Livi, J.R. White, J.L. Adams, and P.R. Young Nature 372 1994 739
10. C. Dominguez, D.A. Powers, and N. Tamayo Curr. Opin. Drug Disc. Dev. 8 2005 421
11. G.F. Ferraccioli Curr. Opin. Anti-Inflammatory Immunomodul. Invest. Drugs 2 2000 74
12. J.J. Haddad Curr. Opin. Investig. Drugs 2 2001 1070
13. D.M. Goldstein, A. Kuglstatter, Y. Lou, and M.J. Soth J. Med. Chem. 53 2010 2345
14. Representative patents include: (a) Angell, R. M.; Aston, N. M.; Bamborough, P.; Bamford, M. J.; Cockerill, G. S.; Flack, S. S.; Laine, D. I.; Merrick, S. J.; Smith, K. J.; Walker, A. L. PCT Int. Appl., WO2003032971, 2003;
15. (c) Almansa, C.; Virgili, M. PCT Int. Appl. WO2007000339, 2007;
16. (c) Zhang, D.; Tasker, A.; Sham, K. K. C.; Chakrabarti, P. P.; Falsey, R. J.; Herberich, B. J.; Pettus, L. H.; Rzasa, R. M. PCT Int. Appl. WO2008045393, 2008;
17. (d) Vidal, B.; Eastwood, P. R.; Gonzalez, J.; Esteve, C. PCT Int. Appl. WO2008107125, 2008.
18. R. Angell, N.M. Aston, P. Bamborough, J.B. Buckton, S. Cockerill, S.J. de Boeck, C.D. Edwards, D.S. Holmes, K.L. Jones, D.I. Laine, S. Patel, P.A. Smee, K.J. Smith, D.O. Somers, and A.L. Walker Bioorg. Med. Chem. Lett. 18 2008 4428
19. R.M. Angell, T.D. Angell, P. Bamborough, M.J. Bamford, C. Chung, S.G. Cockerill, S.S. Flack, K.L. Jones, D.I. Laine, T. Longstaff, S. Ludbrook, R. Pearson, K.J. Smith, P.A. Smee, D.O. Somers, and A.L. Walker Bioorg. Med. Chem. Lett. 18 2008 4433
20. S.T. Wrobleski, S. Lin, J. Hynes, H. Wu, S. Pitt, D.R. Shen, R. Zhang, K.M. Gillooly, D.J. Shuster, K.W. McIntyre, A.M. Doweyko, K.F. Kish, J.A. Tredup, G.J. Duke, J.S. Sack, M. McKinnon, J. Dodd, J.C. Barrish, G.L. Schieven, and K. Leftheris Bioorg. Med. Chem. Lett. 18 2008 2739
21. J. Hynes Jr., A.J. Dyckman, S. Lin, S.T. Wrobleski, Wu Hong, K.M. Gillooly, S.B. Kanner, H. Lonial, D. Loo, K.W. McIntyre, S. Pitt, D.R. Shen, D.J. Shuster, X. Yang, R. Zhang, K. Behnia, H. Zhang, P.H. Marathe, A.M. Doweyko, J.S. Tokarski, J.S. Sack, M. Pokross, S.E. Kiefer, J.A. Newitt, J.C. Barrish, J. Dodd, G.L. Schieven, and K. Leftheris J. Med. Chem. 51 2008 4
22. For further discussion on the 'flip' binding mode of unrelated series see: C.E. Fitzgerald, S.B. Patel, J.W. Becker, P.M. Cameron, D. Zaller, V.B. Pikounis, S.J. O'Keefe, and G. Scapin Nat. Struct. Biol. 10 2003 764
23. S.R. Natarajan, S.T. Heller, K. Nam, S.B. Singh, G. Scapin, S. Patel, J.E. Thompson, C.E. Fitzgerald, and S.J. O'Keefe Bioorg. Med. Chem. Lett. 16 2006 5809
24. A.S. Kende, and J.C. Hodges Synth. Commun. 12 1982 1
25. D.W. Robertson, J.H. Krushinski, G.D. Pollock, H. Wilson, R.F. Kauffman, and J.S. Hayes J. Med. Chem. 30 1987 824
26. Di, M. A.; Foulon, L.; Garcia, G.; Nisato, D.; Roux, R.; Serradeil-Legal, C.; Valette, G.; Wagnon, J. Eur. Pat. Appl., EP636608, 1995.
27. For full details of the biological assays used in this publication see: W. Lumeras, F. Caturla, L. Vidal, C. Esteve, C. Balagué, A. Orellana, M. Domínguez, R. Roca, J.M. Huerta, N. Godessart, and B. Vidal J. Med. Chem. 52 2009 5531
28. Eastwood, P. et al., unpublished results.
29. Crumb, W. J.; Cavero, I. Current Protocols in Pharmacology 2003, Online ISBN: 9780471141754, 10.8.1-10.8.18.