3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 15, 2003, Pages 2465-2468

  Liu, Jin Jun ^a   Dermatakis, Apostolos ^a   Lukacs, Christine ^a   Konzelmann, Fred ^a   Chen, Yi ^a   Kammlott, Ursula ^a   Depinto, Wanda ^a   Yang, Hong ^a   Yin, Xuefeng ^a   Chen, Yingsi ^a   Schutt, Andy ^a   Simcox, Mary Ellen ^a   Luk, Kin Chun ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; ANTIMETABOLITE; ANTINEOPLASTIC AGENT; BROXURIDINE; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; DIAGNOSTIC AGENT; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; ENZYME INHIBITOR; NAPHTHALENE DERIVATIVE; PYRROLE DERIVATIVE; TETRAZOLIUM; THIAZOLE DERIVATIVE; THIAZOLYL BLUE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELL ACTIVITY; CELL CYCLE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; CHEMICAL STRUCTURE; CONFORMATION; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFECT; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYDROGEN BOND; IN VITRO STUDY; OXIDATION REDUCTION REACTION; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

EID: 10744231650     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00488-8     Document Type: Article

References (24)

1. (a) Keyomarsi, K., Grana, X. In Progress in Cell Cycle Research: Meijer, L., G., Philippe, M., Eds.; Plenum Press: New York, 1997; p 171. (b) Pines J. Semin. Cancer Biol. 5:1994;305.
2. (a) Keyomarsi, K., Grana, X. In Progress in Cell Cycle Research: Meijer, L., G., Philippe, M., Eds.; Plenum Press: New York, 1997; p 171. (b) Pines J. Semin. Cancer Biol. 5:1994;305.
3. (a) Morgan D.O. Nature. 374:1995;131 (b) Hunter T., Pines J. Cell. 79:1994;573 (c) Sherr C. Science. 274:1996;1672.
4. (a) Morgan D.O. Nature. 374:1995;131 (b) Hunter T., Pines J. Cell. 79:1994;573 (c) Sherr C. Science. 274:1996;1672.
5. (a) Morgan D.O. Nature. 374:1995;131 (b) Hunter T., Pines J. Cell. 79:1994;573 (c) Sherr C. Science. 274:1996;1672.
6. Webster K.R., Kimball S.D. Emerg. Drugs. 5:2000;45.
7. (a) Pines J. Semin. Cancer Biol. 6:1995;63 (b) Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnik M.H. Science. 264:1994;436 (c) Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A. Nature. 368:1994;753 (d) Hartwell L.H., Kastan M.B. Science. 266:1994;1821.
8. (a) Pines J. Semin. Cancer Biol. 6:1995;63 (b) Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnik M.H. Science. 264:1994;436 (c) Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A. Nature. 368:1994;753 (d) Hartwell L.H., Kastan M.B. Science. 266:1994;1821.
9. (a) Pines J. Semin. Cancer Biol. 6:1995;63 (b) Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnik M.H. Science. 264:1994;436 (c) Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A. Nature. 368:1994;753 (d) Hartwell L.H., Kastan M.B. Science. 266:1994;1821.
10. (a) Pines J. Semin. Cancer Biol. 6:1995;63 (b) Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnik M.H. Science. 264:1994;436 (c) Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A. Nature. 368:1994;753 (d) Hartwell L.H., Kastan M.B. Science. 266:1994;1821.
11. (a) Donnellan R., Chetty R. FASEB J. 13:1999;773 (b) Paulovich A.G., Toczyski D.P., Hartwell L.H. Cell. 88:1997;315 (c) Pardee A.B. Proc. Natl. Acad. Sci. U.S.A. 71:1974;1286.
12. (a) Donnellan R., Chetty R. FASEB J. 13:1999;773 (b) Paulovich A.G., Toczyski D.P., Hartwell L.H. Cell. 88:1997;315 (c) Pardee A.B. Proc. Natl. Acad. Sci. U.S.A. 71:1974;1286.
13. (a) Donnellan R., Chetty R. FASEB J. 13:1999;773 (b) Paulovich A.G., Toczyski D.P., Hartwell L.H. Cell. 88:1997;315 (c) Pardee A.B. Proc. Natl. Acad. Sci. U.S.A. 71:1974;1286.
14. (a) Kim K., Kimball D., Misra R., Rawlins D., Hunt J., Xiao H.Y., Lu S., Qian L., Han W.C., Shan W., Mitt T., Cai Z.C., Poss M., Zhu H., Sack J., Tokarski J.S., Chang C.Y., Pavletich N., Kamath A., Humphreys W.A., Marathe P., Bursuker B., Kellar K., Roongta U., Batorsky B., Mulheron J., Bol D., Fairchild C., Lee F., Webster K. J. Med. Chem. 45:2002;3905
15. (b) Bramson H.N., Corona J., Davis S.T., Dickerson S.H., Edelstein M., Frye S.V., Gampe R.T., Harris P.A., Hassell A., Holmes W.D., Hunter R.N., Lackey K.E., Lovejoy B., Luzzio M.J., Montana V., Rocque W.J., Rusnak D., Shewchuk L., Veal J.M., Walker D.H., Kuyper L.F. J. Med. Chem. 44:2001;4339 (c) Barvian M., Boschelli D.H., Cossrow J., Dobrusin E., Fattaey A., Fritsch A., Fry D., Harvey P., Keller P., Garrett M., Leopold W., McNamara D., Quin M., Trumpp-Kallmeyer S., Toogood P., Wu Z., Zhang E. J. Med. Chem. 43:2000;4606.
16. (a) Kim K., Kimball D., Misra R., Rawlins D., Hunt J., Xiao H.Y., Lu S., Qian L., Han W.C., Shan W., Mitt T., Cai Z.C., Poss M., Zhu H., Sack J., Tokarski J.S., Chang C.Y., Pavletich N., Kamath A., Humphreys W.A., Marathe P., Bursuker B., Kellar K., Roongta U., Batorsky B., Mulheron J., Bol D., Fairchild C., Lee F., Webster K. J. Med. Chem. 45:2002;3905 (b) Bramson H.N., Corona J., Davis S.T., Dickerson S.H., Edelstein M., Frye S.V., Gampe R.T., Harris P.A., Hassell A., Holmes W.D., Hunter R.N., Lackey K.E., Lovejoy B., Luzzio M.J., Montana V., Rocque W.J., Rusnak D., Shewchuk L., Veal J.M., Walker D.H., Kuyper L.F. J. Med. Chem. 44:2001;4339 (c) Barvian M., Boschelli D.H., Cossrow J., Dobrusin E., Fattaey A., Fritsch A., Fry D., Harvey P., Keller P., Garrett M., Leopold W., McNamara D., Quin M., Trumpp-Kallmeyer S., Toogood P., Wu Z., Zhang E. J. Med. Chem. 43:2000;4606.
17. (a) Liu J.J., Konzelmann F., Luk K.C. Tetrahedron Lett. 44:2003;2545
18. (a) Liu J.J., Konzelmann F., Luk K.C. Tetrahedron Lett. 44:2003;2545 (b) Liu J.J., Konzelmann F., Luk K.C. Tetrahedron. Lett. 44:2003;3901.
19. Chen, Y.; Corbett, W. L.; Dermatakis, A.; Liu, J. J.; Luk, K. C.; Mahaney, P. E.; Mischke, S. G. WO 0035908, 2000.
20. Davis, S. T.; Dickerson, S. H.; Frye, S. V.; Harris, P. A.; Hunter, R. N.; Kuyper, L. F.; Lackey, K. E.; Luzzio, M. J.; Veal, J. M.; Walker, D. H. WO 9915500, 1999.
21. (a) Sun L., Tran N., Tang F., App H., Hirth P., McMahon G., Tang C. J. Med. Chem. 41:1998;2588
22. (a) Sun L., Tran N., Tang F., App H., Hirth P., McMahon G., Tang C. J. Med. Chem. 41:1998;2588 (b) Fong T.A.T., Shawver L.K., Sun L., Tang C., App H., Powell T., Kim Y., Schreck R., Wang X., Risau W., Ullrich A., Hirth K.P., McMahon G. Cancer Res. 59:1999;99.
23. Davis S.T., Benson B.G., Bramson H.N., Chapman D.E., Dickerson S.H., Dold K.M., Eberwein D.J., Edelstein M., Frye S.V., Gampe R.T. Jr., Griffin R.J., Harris P.A., Hassell A.M., Holmes W.D., Hunter R.N., Knick V.B., Lackey K., Lovejoy B., Luzzio M.J., Murray D., Parker P., Rocque W.J., Shewchuk L., Veal J.M., Walker D.H., Kuyper L.F. Science. 291:2001;134.
24. Crystals of the CDK2:7b complex were grown at 4°C by the vapor diffusion method. CDK2(1-298) at 12 mg/mL was mixed with and equilibrated against 10% PEG 3350, 0.2 M ammonium phosphate, 0.1 M Bicine pH 9.0. 2% β-mercaptoethanol was added to the reservoir after mixing of the drop. Cryoprotectant was the same as the reservoir with 20% PEG 3350 and the addition of 15% ethylene glycol. X-ray data was collected at beamline X8C at Brookhaven National Laboratories. Data was processed to 2.5 Å with the HKL package (Otwinowski, Z., Minor, W. Methods Enzymol. 1997, 276, 307) to an R-sym of 0.071. The structure was determined by molecular replacement using AmoRe (Navaza, J. Acta Crystallogr. 1994, A50, 157) and was refined with CNX (CNX v.99.0-BETA, Molecular Simulations Inc.) to an R-factor/Rfree of 0.208/0.279. Coordinates have been deposited to the PDB under accession code 1p2a.