Discovery and design of benzimidazolone based inhibitors of p38 MAP kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 24, 2006, Pages 6316-6320

  Hammach, Abdelhakim ^a   Barbosa, Antonio ^a   Gaenzler, Faith Corbo ^a   Fadra, Tazmeen ^a   Goldberg, Daniel ^a   Hao, Ming Hong ^a   Kroe, Rachel R ^a   Liu, Pingrong ^a   Qian, Kevin C ^a   Ralph, Mark ^a   Sarko, Christopher ^a   Soleymanzadeh, Fariba ^a   Moss, Neil ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

Benzimidazolone; Inhibitor; p38 MAP kinase

Indexed keywords

BENZIMIDAZOLONE DERIVATIVE; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFECT; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

BENZIMIDAZOLES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33750713651     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.09.014     Document Type: Article

References (21)

1. Klinkhoff A. Drugs 64 (2004) 1267
2. Barry J., and Kirby B. Expert Opin. Biol. Ther. 4 (2004) 975
3. Saklatvala J. Curr. Opin. Pharm. 4 (2004) 372
4. Kumar S., Boehm J., and Lee J.C. Nat. Rev. Drug Discov. 2 (2003) 717
5. Ono K., and Han J. Cell. Signalling 12 (2000) 1
6. Jakckson P.F., and Bullington J.L. Curr. Top. Med. Chem. 2 (2002) 1009
7. Cirillo P., Pargellis C., and Regan J. Curr. Top. Med. Chem. 2 (2002) 1021
8. Regan J., Breitfelder S., Cirillo P., Gilmore T., Graham A.G., Hickey E.R., Klaus B., Madwed J., Moriak M., Moss N., Pargellis C.A., Pav S., Proto A., Swinamer A., Tong L., and Torcellini C. J. Med. Chem. 45 (2002) 2994
9. Regan J., Capolino A., Cirillo P.F., Gilmore T., Graham A.G., Hickey E., Kroe R.R., Madwed J., Moriak M., Nelson R., Pargellis C.A., Swinamer A., Torcellini C., Tsang M., and Moss N. J. Med. Chem. 46 (2003) 4676
10. m values determined for a range of known Phe-in p38 inhibitors. {A figure is presented}
11. 50s for RO3201195, SB203580, VX-745, and L779,450 have been disclosed in the following references, respectively. Goldstein D.M., and Gabriel T. Curr. Top. Med. Chem. 5 (2005) 1017
12. Lee J.C., Laydon J.T., McDonnell P.C., Gallageher T.F., Kumar S., Green D., Blumenthal M.J., Heys J.R., Landvatter S.W., Strickler J.E., McLaughlin M.M., Siemens I.R., Fisher S.M., Livi G.P., White J.R., Adams J.L., and Young P.R. Nature 372 (1994) 739
13. Salutoro, F. G. In 27th National Medicinal Chemistry Symposium, Kansa City, MO, June 13-17, 2000.
14. Liverton N.J., Butcher J.W., Claiborne C.F., Claremon D.A., Libby B.E., Nguyen K.T., Pitzenberger S.M., Selnick H.G., Smith G.R., Tebben A., Vacca J.P., Varga S.L., Agarwal L., Dancheck K., Forsyth A.J., Fletcher D.S., Frantz B., Hanlon W.A., Harper C.F., Hofsess S.J., Kostura M., Lin J., Luell S., O'Neill E.A., Orevillo C.J., Pang M., Parsons J., Rolando A., Sahly Y., Visco D.M., and O'Keefe S.J. J. Med. Chem. 42 (1999) 2180
15. Chan D.M.T., Monaco K.L., Wang R.P., and Winters M.P. Tetrahedron Lett. 39 (1998) 2933
16. Lam P.Y.S., Clark C.G., Saubern S., Adams J., Winters M.P., Chan D.M.T., and Combs A. Tetrahedron Lett. 39 (1998) 2941
17. Evans D.A., Katz J.L., and West T.R. Tetrahedron Lett. 39 (1998) 2937
18. Lam P.Y.S., Clark C.G., Saubern S., Adams J., Averill K., Chan D.M.T., and Combs A.P. Synlett (2000) 674
19. Revesz L., Blum E., Di Padova F.E., Buhl T., Feifel R., Gram H., Hiestand P., Manning U., and Rucklin G. Bioorg. Med. Chem. Lett. 14 (2004) 3601
20. Revesz L., Di Padova F.E., Buhl T., Feifel R., Gram H., Hiestand P., Manning U., Wolf R., and Zimmerlin A.G. Bioorg. Med. Chem. Lett. 12 (2002) 2109
21. Moffat D., Davis P., Hutchings M., Davis J., Berg D., Batchelor M., Johnson J., O'Connell J., Martin R., Carabbe T., Delgado J., and Perry M. Bioorg. Med. Chem. Lett. 9 (1999) 3351