Enhanced selectivity profile of pyrazole-urea based DFG-out p38α inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 16, 2010, Pages 4885-4891

  Liu, Hu ^a   Kuhn, Cyrille ^a   Feru, Frederic ^a   Jacques, Suzanne L ^a   Deshmukh, Gayatri D ^a   Ye, Ping ^a   Rennie, Glen R ^a   Johnson, Theresa ^a   Kazmirski, Steven ^a   Low, Simon ^a   Coli, Rocco ^a   Ding, Yuan Hua ^a   Cheng, Alan C ^a   Tecle, Haile ^a   English, Jessie M ^a   Stanton, Robert ^a   Wu, Joe C ^a  

^a PFIZER INC   (United States)

Author keywords

DFG out; Kinase inhibitor; p38; Pyrazole urea

Indexed keywords

DORAMAPIMOD; IMATINIB; MITOGEN ACTIVATED PROTEIN KINASE 14; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; SORAFENIB; UREA DERIVATIVE; ADENINE; CARBANILAMIDE DERIVATIVE; PROTEIN KINASE INHIBITOR;

ARTICLE; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; AMINO ACID SEQUENCE; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; METABOLISM; MICROSOME; PROTEIN MOTIF; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADENINE; AMINO ACID MOTIFS; AMINO ACID SEQUENCE; BINDING SITES; HUMANS; MICROSOMES; MITOGEN-ACTIVATED PROTEIN KINASE 14; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77955428704     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.06.073     Document Type: Article

References (24)

1. M. Rincon Curr. Opin. Immunol. 13 2001 339
2. K. Kuida, and D.M. Boucher J. Biol. Chem. 135 2004 653
3. G.L. Johnson, and R. Lapadat Science 298 2002 1911
4. G. Schett, J. Zwerina, and G. Firestein Ann. Rheum. Dis. 67 2008 909
5. M. Gaestel, A. Mengel, U. Bothe, and K. Asadullah Curr. Med. Chem. 14 2007 2214
6. L. Sizova Br. J. Clin. Pharmacol. 66 2008 173
7. J.R. Lutt, and A. Deodhar Drugs 68 2008 591
8. L.H. Pettus, and R.P. Wurz Curr. Top. Med. Chem. 8 2008 1452
9. C. Peifer, G. Wagner, and S. Laufer Curr. Top. Med. Chem. 6 2006 113
10. D.M. Goldstein, and T. Gabriel Curr. Top. Med. Chem. 5 2005 1017
11. A.L. Gill, M. Verdonk, R.G. Boyle, and R. Taylor Curr. Top. Med. Chem. 7 2007 1408
12. J.J.-L. Liao J. Med. Chem. 50 2007 409
13. B. Okram, A. Nagle, F.J. Adrian, C. Lee, P. Ren, X. Wang, T. Sim, Y. Xie, X. Wang, G. Xia, G. Spraggon, M. Warmuth, Y. Liu, and N.S. Gray Chem. Biol. 13 2006 779
14. Y. Liu, and N.S. Gray Nat. Chem. Biol. 2 2006 358
15. M. Sawa Mini-Rev. Med. Chem. 8 2008 1291
16. B.A. Mueller Curr. Pharm. Design 15 2009 120
17. N. Mendez-Sanchez, F. Vasquez-Fernandez, D. Zamora-Valdes, and M. Uribe Ann. Hepatol. 7 2008 46
18. J. Regan, S. Breitfelder, P. Cirillo, T. Gilmore, A.G. Graham, E.R. Hickey, B. Klaus, J. Madwed, M. Moriak, N. Moss, C.A. Pargellis, S. Pav, A. Proto, A. Swinamer, L. Tong, and C. Torcellini J. Med. Chem. 45 2002 2994
19. J. Regan, A. Capolino, P.F. Cirillo, T. Gilmore, A.G. Graham, E. Hickey, R.R. Kroe, J. Madwed, M. Moriak, R. Nelson, C.A. Pargellis, A. Swinamer, C. Torcellini, M. Tsang, and N. Moss J. Med. Chem. 46 2003 4676
20. N. Moss, S. Breitfelder, R. Betageri, P.F. Cirillo, T. Fadra, E.R. Hickey, T. Kirrane, R.R. Kroe, J. Madwed, R.M. Nelson, C.A. Pargellis, K.C. Qian, J. Regan, A. Swinamer, and C. Torcellini Bioorg. Med. Chem. Lett. 17 2007 4242
21. C. Pargellis, L. Tong, L. Churchill, P.F. Cirillo, T. Gilmore, A.G. Graham, P.M. Grob, E.R. Hickey, N. Moss, S. Pav, and J. Regan Nat. Struct. Biol. 9 2002 268
22. A. Card, C. Caldwell, H. Min, B. Lokchander, H. Xi, S. Sciabola, A.V. Kamath, S.L. Clugston, W.R. Tschantz, L. Wang, and D.J. Moshinsky J. Biomol. Screen 141 2009 31
23. H. Tecle, F. Feru, H. Liu, C. Kuhn, G. Rennie, M. Morris, J. Shao, A.C. Chang, D. Gikunju, J. Miret, R. Coli, S. Xi, S.L. Clugston, S. Low, S. Kazmirski, Y.-H. Ding, Q. Cao, T.L. Johnson, G.D. Deshmukh, J.P. DiNitto, J.C. Wu, and J.M. English Chem. Biol. Drug Des. 74 2009 547
24. The p-38α co-crystals with this class of compounds are often partially resolved for the ligands. Nevertheless, based on some of the partially resolved structures, it is clear that these ureas bind to the 'DFG-out' conformation of the protein.