Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 12, Issue 20, 2002, Pages 2989-2992

  Berger, Dan ^a   Dutia, Minu ^a   Powell, Dennis ^a   Wissner, Allan ^a   DeMorin, Frenel ^a   Raifeld, Yuri ^a   Weber, Jennifer ^a   Boschelli, Frank ^a  

^a WYETH RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 ANILINO 7 PHENYL 3 QUINOLINECARBONITRILE; HYDROGEN; PHOSPHOTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CELL TRANSFORMATION; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; FIBROBLAST;

ENZYME INHIBITORS; INDICATORS AND REAGENTS; NITRILES; QUINOLINES; SRC-FAMILY KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037152464     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00577-2     Document Type: Article

References (27)

1. Boschelli D.H., Boschelli F. Drugs Future. 25:2000;717.
2. (a) Bjorge J.D., Jakymiw A., Fujita D.J. Oncogene. 19:2000;5620.
3. (b) Irby R.B., Yeatman T.J. Oncogene. 19:2000;5636.
4. (a) Missbach M., Altmann E., Susa M. Curr. Opin. Drug Discov. Dev. 3:2000;541.
5. (b) Susa M., Teti A. Drug News Perspect. 13:2000;169.
6. Paul R., Zhang Z.G., Eliceiri B.P., Jiang Q., Boccia A.D., Zhang R.L., Chopp M., Cheresh D.A. Nat. Med. 7:2001;222.
7. Myers M.R., Setzer N.N., Spada A.P., Zulli A.L., Hsu C.-Y.J., Zilberstein A., Johnson S.E., Hook L.E., Jacoski M.V. Bioorg. Med. Chem. Lett. 7:1997;417.
8. Hanke J.H., Gardner J.P., Dow R.L., Changelian P.S., Brissette W.H., Weringer E.J., Pollok B.A., Connelly P.A. J. Biol. Chem. 271:1996;695.
9. (a) Missbach M., Altmann E., Widler L., Susa M., Buchdunger E., Mett H., Meyer T., Green J. Bioorg. Med. Chem. Lett. 10:2000;945.
10. (b) Widler L., Green J., Missbach M., Susa M., Altmann E. Bioorg. Med. Chem. Lett. 11:2001;849.
11. © Altmann E., Missbach M., Green J., Susa M., Wagenknecht H.-A., Widler L. Bioorg. Med. Chem. Lett. 11:2001;853.
12. (d) Arnold L.D., Calderwood D.J., Dixon R.W., Johnston D.N., Kamens J.S., Munschauer R., Rafferty P., Ratnofsky S.E. Bioorg. Med. Chem. Lett. 10:2000;2167.
13. (e) Burchat A.F., Calderwood D.J., Hirst G.C., Holman N.J., Johnston D.N., Munschauer R., Rafferty P., Tometzki G.B. Bioorg. Med. Chem. Lett. 10:2000;2171.
14. Klutchko S.R., Hamby J.M., Boschelli D.H., Wu Z.P., Kraker A.J., Amar A.M., Hartl B.G., Shen C., Klohs W.D., Steinkampf R.W., Driscoll D.L., Nelson J.M., Elliott W.L., Roberts B.J., Stoner C.L., Vincent P.W., Dykes D.J., Panek R.L., Lu G.H., Major T.C., Dahring T.K., Hallak H., Bradford L.A., Showalter H.D.H., Doherty A.M. J. Med. Chem. 41:1998;3276.
15. Thompson A.M., Rewcastle G.W., Boushelle S.L., Hartl B.G., Kraker A.J., Lu G.H., Batley B.L., Panek R.L., Showalter H.D.H., Denny W.A. J. Med. Chem. 43:2000;3134.
16. Schroeder M.C., Hamby J.M., Connolly C.J.C., Grohar P.J., Winters R.T., Barvian M.R., Morre C.W., Boushelle S.L., Crean S.M., Kraker A.J., Driscoll D.L., Vincent P.W., Elliott W.L., Lu G.H., Batley B.L., Dahring T.K., Major T.C., Panek R.L., Doherty A.M., Showalter H.D.H. J. Med. Chem. 44:2001;1915.
17. Wissner A., Berger D.M., Boschelli D.H., Floyd M.B., Greenberger L.M., Gruber B.C., Johnson B.D., Mamuya N., Nilakantan R., Reich M.F., Shen R., Tsou H.R., Upeslacis E., Wang Y.F., Wu B., Ye F., Zhang N. J. Med. Chem. 43:2000;3244.
18. (a) Boschelli D.H., Wang D.Y., Ye F., Wu B., Zhang N., Dutia M., Powell D.W., Wissner A., Arndt K., Weber J.M., Boschelli F. J. Med. Chem. 44:2001;822.
19. (b) Wang D.Y., Miller K., Boschelli D.H., Ye F., Wu B., Floyd M.B., Powell D.W., Wissner A., Weber J.M., Boschelli F. Bioorg. Med. Chem. Lett. 10:2000;2477.
20. © Boschelli D.H., Ye F., Wang D.Y., Dutia M., Johnson S., Wu B., Miller K., Powell D.W., Arndt K., Discafani C., Etienne C., Gibbons J., Grod J., Lucas J., Weber J.M., Boschelli F. J. Med. Chem. 44:2001;3965.
21. (a) Zhang N., Wu B., Powell D., Wissner A., Floyd M.B., Kovacs E.D., Toral-Barza L., Kohler C. Bioorg. Med. Chem. Lett. 10:2000;2825.
22. (b) Zhang N., Wu B., Eudy N., Wang Y., Ye F., Powell D., Wissner A., Feldberg L.R., Kim S.C., Mallon R., Kovacs E.D., Toral-Barza L., Kohler C.A. Bioorg. Med. Chem. Lett. 11:2001;1407.
23. Boschelli, D. H.; Wang, D. Y.; Ye, F.; Yamashita, A.; Zhang, N.; Powell, D. W.; Weber, J. M.; Boschelli, F. Bioorg. Med. Chem. Lett. 2002, 12, 2011.
24. Ishiyama T., Murata M., Miyoura N. J. Org. Chem. 60:1995;7508.
25. A typical preparation of target compounds 15a-k is illustrated by the following procedure for 15f: To a dry flask under a nitrogen atmosphere was added 200 mg (0.78 mmol) of 5a, 0.218 g (0.86 mmol) of bis(pinacolato)diboron, 230 mg (2.34 mmol) of potassium acetate, 5 mL of dimethylsulfoxide and 32 mg (0.04 mmol) of [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane. The reaction mixture was heated at 80°C for 2 h. After cooling, the mixture was partitioned between 20 mL of toluene, 40 mL of ethyl acetate and 40 mL of water. The layers were separated and the aqueous layer was further extracted with 30 mL of ethyl acetate. The organic layers were combined and washed with 4×40 mL water. After drying over magnesium sulfate, removal of the solvents gave crude 4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]morpholine as a dark oil.
26. 2: calcd: C, 56.91; H, 5.20; N, 10.30. Found: C, 57.20; H, 5.10; N, 9.91.
27. 12a-c Peptide was bound to the streptavidin plate prior to the kinase reaction, and peptide phosphorylation reaction was monitored by europium fluorescence as recommended by the manufacturer (Perkin-Elmer). For cell assays, Costar ultra-low binding plates were coated with Sigma-Cote to block residual cell attachment.