Imidazopyrimidines, potent inhibitors of p38 MAP kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 3, 2003, Pages 347-350

  Rupert, Kenneth C ^a   Henry, James R ^a,b   Dodd, John H ^a,c   Wadsworth, Scott A ^a   Cavender, Druie E ^a   Olini, Gilbert C ^a   Fahmy, Bohumila ^a   Siekierka, John J ^a  

^a Drug Discovery Raritan   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ANTIINFLAMMATORY AGENT; IMIDAZOPYRIDINE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; MOUSE; NONHUMAN;

CATALYSIS; ENZYME INHIBITORS; IMIDAZOLES; INDICATORS AND REAGENTS; MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0037330356     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)01020-X     Document Type: Article

References (18)

1. (a) Brennan F.M., Feldman M. Curr. Opin. Immunol. 8:1996;87.
2. (b) Camussi G., Lupia E. Drugs. 55:1998;613.
3. Gallagher T.F., Seibel G.L., Kassis S., Laydon J.T., Blumenthal M.J., Lee J.C., Lee D., Boehm J.C., Fier-Thompson S.M., Abt J.W., Sorenson M.E., Smietana J.M., Hall R.F., Garigipati R.S., Bender P.E., Erhard K.F., Krog A.J., Hofmann G.A., Sheldrake P.L., McDonnell P.C., Kumar S., Young P.R., Adams J.L. Bioorg. Med. Chem. 5:1997;49.
4. (a) Jackson P.F., Bullington J.L. Curr. Top. Med. Chem. 2:2002;1011.
5. (b) Cirillo P.F., Pargellis C., Regan J. Curr. Top. Med. Chem. 2:2002;1021.
6. (c) Badger A.M., Bradbeer J.N., Votta B., Lee J.C., Adams J.L., Griswold D.E. J. Pharmacol. Exp. Ther. 279:1996;1453.
7. (d) Henry J.R., Cavender D.E., Wadsworth S.A. Drugs Future. 24:1999;1345.
8. (e) Wadsworth S.A., Cavender D.E., Beers S.A., Lalan P., Schafer P.H., Malloy E.A., Wu W., Fahmy B., Olini G.C., Davis J.E., Pellegrino-Gensey J.L., Watcher M.P., Siekierka J.J. J. Pharmacol. Exp. Ther. 291:1999;680.
9. (a) Henry J.R., Rupert K.C., Dodd J.H., Turchi I.J., Wadsworth S.A., Cavender D.E., Fahmy B., Olini G.C., Davis J.E., Pellegrino-Gensey J.L., Schafer P.H., Siekierka J.J. J. Med. Chem. 41:1998;4196.
10. (b) Henry J.R., Rupert K.C., Dodd J.H., Turchi I.J., Wadsworth S.A., Cavender D.E., Schafer P.H., Siekierka J.J. Bioorg. Med. Chem. Lett. 8:1998;3335.
11. (c) Henry J.R., Dodd J.H. Tetrahedron Lett. 39:1998;8763.
12. (d) Dodd, J. H.; Henry, J. R.; Rupert, K. C. PCT Int. Appl. WO 98/47899.
13. Dodd, J. H.; Henry, J. R.; Rupert, K. C. U.S. Patent 6,147,096.
14. Dodd, J. H.; Henry, J. R.; Rupert, K. C. PCT Int. Appl. WO 01/34605.
15. 33P-ATP (3000 Ci/mmol, Amersham Life Science, Arlington Heights, IL), with or without test compounds or vehicle (DMSO, 2% final concentration), in a total volume of 60 μL, in a round-bottom polypropylene 96-well plate. After 30 min at 30°C, reactions were stopped and proteins precipitated by the addition of 60 μL/well of 50% trichloroacetic acid (TCA), and the precipitates transferred to a 96-well Durapore membrane filterplate (Millipore, Bedford, MA). Wells were filtered using a Millipore vacuum manifold, washed 5× with 200 μL/well of 10% TCA/10 mM sodium phosphate, and briefly air-dried. Thirty μL/well of Microscint-20 scintillant (Packard, Meriden, CT) was added, the plate sealed with plastic film (Packard), and counted in a Packard TopCount microplate scintillation counter.
16. 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., O'Keefe S.J. J. Med. Chem. 42:1999;2180.
17. (a) Collis A.J., Foster M.L., Halley F., Maslen C., McLay I.M., Page K.M., Redford E.J., Souness J.E., Wilsher N.E. Bioorg. Med. Chem. Lett. 11:2001;693.
18. (b) Adams J.L., Boehm J.C., Kassis S., Gorycki P.D., Webb E.F., Hall R., Sorenson M., Lee J.C., Ayrton A., Griswold D.E., Gallagher T.F. Bioorg. Med. Chem. Lett. 8:1998;3111.