Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 17, 2014, Pages 4910-4916

  Edupuganti, Ramakrishna ^a,b   Wang, Qiantao ^a,c   Tavares, Clint D J ^a   Chitjian, Catrina A ^a   Bachman, James L ^b   Ren, Pengyu ^c   Anslyn, Eric V ^b   Dalby, Kevin N ^a  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b The University of Texas at Austin   (United States)

^c The University of Texas at Austin   (United States)

Author keywords

eEF 2K inhibitor; Homology modeling; Kinase inhibitor; Pyrido 2,3 d pyrimidine 2,4 dione; Uracil

Indexed keywords

6 AMINO 1 ALKYL 3 ALKYLPYRIMIDINE 2,4(1H,3H) DIONE; 6 AMINO 1 CYCLOPROPYL 3 ETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBALDEHYDE; 6 AMINO 1 CYCLOPROPYL 3 ETHYLPYRIMIDINE 2,4(1H,3H) DIONE; 6 AMINO 1 CYCLOPROPYL 3 PROPYLPYRIMIDINE 2,4(1H,3H) DIONE; 6 AMINO 1,3 DIETHYLPYRIMIDINE 2,4(1H,3H) DIONE; 7 AMINO 1 CYCLOPROPYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO 1 CYCLOPROPYL 2,4 DIOXO 3 PROPYL 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO 1 CYCLOPROPYL 3 ETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBONITRILE; 7 AMINO 1 CYCLOPROPYL 3 ETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOTHIOAMIDE; 7 AMINO 1 CYCLOPROPYL 3 ETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO 1,3 DIETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO 1,3 DIMETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO 3 (4 AMINOBENZYL) 1 CYCLOPROPYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO CYCLOPROPYL 3 (4 NITROBENZYL) 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; 7 AMINO CYCLOPROPYL 3 METHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXAMIDE; ELONGATION FACTOR 2 KINASE; ETHYL 7 AMINO 1 CYCLOPROPYL 3 ETHYL 2,4 DIOXO 1,2,3,4 TETRAHYDROPYRIDO[2,3 D]PYRIMIDINE 6 CARBOXYLATE; PYRIDO[2,3 D]PYRIMIDINE 2,4 DIONE DERIVATIVE; PYRIDO[2,3 D]PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; EEF2K PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE; PYRIMIDINONE DERIVATIVE; RECOMBINANT PROTEIN;

ALKYLATION; ANIMAL CELL; ARTICLE; BINDING AFFINITY; BREAST CANCER; CANCER CELL; CELL ACTIVITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BINDING; DRUG DESIGN; DRUG EFFICACY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME ACTIVITY; GLYCOLYSIS; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; NONHUMAN; PROSTATE CANCER; PROTEIN PHOSPHORYLATION; STRUCTURE ACTIVITY RELATION; UTERINE CERVIX CANCER; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; METABOLISM; SYNTHESIS; TUMOR CELL CULTURE;

EUKARYOTA;

DOSE-RESPONSE RELATIONSHIP, DRUG; ELONGATION FACTOR 2 KINASE; HUMANS; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PYRIDINES; PYRIMIDINONES; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 84906937433     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.06.050     Document Type: Article

References (27)

1. A.G. Ryazanov, E.A. Shestakova, and P.G. Natapov Nature 334 1988 170
2. N.T. Redpath, N.T. Price, K.V. Severinov, and C.G. Proud Eur. J. Biochem. 213 1993 689
3. C.G. Proud Biochem. J. 403 2007 217
4. G. Leprivier, M. Remke, B. Rotblat, A. Dubuc, A.R. Mateo, M. Kool, S. Agnihotri, A. El-Naggar, B. Yu, S.P. Somasekharan, B. Faubert, G. Bridon, C.E. Tognon, J. Mathers, R. Thomas, A. Li, A. Barokas, B. Kwok, M. Bowden, S. Smith, X. Wu, A. Korshunov, T. Hielscher, P.A. Northcott, J.D. Galpin, C.A. Ahern, Y. Wang, M.G. McCabe, V.P. Collins, R.G. Jones, M. Pollak, O. Delattre, M.E. Gleave, E. Jan, S.M. Pfister, C.G. Proud, W.B. Derry, M.D. Taylor, and P.H. Sorensen Cell 153 2013 1064
5. T.G. Parmer, M.D. Ward, E.J. Yurkow, V.H. Vyas, T.J. Kearney, and W.N. Hait Br. J. Cancer 79 1999 59
6. D.M. Bagaglio, and W.N. Hait Cell Growth Differ. 5 1994 1403
7. A. Nilsson, and O. Nygard Biochim. Biophys. Acta 1268 1995 263
8. A.A. Ashour, A.A. Abdel-Aziz, A.M. Mansour, S.N. Alpay, L. Huo, and B. Ozpolat Apoptosis 19 2014 241
9. W.N. Hait, H. Wu, S. Jin, and J.M. Yang Autophagy 2 2006 294
10. M. Gschwendt, W. Kittstein, and F. Marks FEBS Lett. 338 1994 85
11. S.P. Soltoff Trends Pharmacol. Sci. 28 2007 453
12. T.G. Parmer, M.D. Ward, and W.N. Hait Cell Growth Differ. 8 1997 327
13. S.I. Cho, M. Koketsu, H. Ishihara, M. Matsushita, A.C. Nairn, H. Fukazawa, and Y. Uehara Biochim. Biophys. Acta. 1475 2000 207
14. S. Arora, J.M. Yang, T.G. Kinzy, R. Utsumi, T. Okamoto, T. Kitayama, P.A. Ortiz, and W.N. Hait Cancer Res. 63 2003 6894
15. A.K. Devkota, C.D. Tavares, M. Warthaka, O. Abramczyk, K.D. Marshall, T.S. Kaoud, K. Gorgulu, B. Ozpolat, and K.N. Dalby Biochemistry 51 2012 2100
16. J.W. Lockman, M.D. Reeder, K. Suzuki, K. Ostanin, R. Hoff, L. Bhoite, H. Austin, V. Baichwal, and J. Adam Willardsen Bioorg. Med. Chem. Lett. 20 2010 2283
17. A.K. Devkota, M. Warthaka, R. Edupuganti, C.D. Tavares, W.H. Johnson, B. Ozpolat, E.J. Cho, and K.N. Dalby J. Biomol. Screen. 19 2014 445
18. Z. Chen, S.M. Gopalakrishnan, M.H. Bui, N.B. Soni, U. Warrior, E.F. Johnson, J.B. Donnelly, and K.B. Glaser J. Biol. Chem. 286 2011 43951
19. M.I. Nieto, M.C. Balo, J. Brea, O. Caamaño, M.I. Cadavid, F. Fernández, X.G. Mera, C. López, and J.E. Rodríguez-Borges Bioorg. Med. Chem. 17 2009 3426
20. K. Hirota, Y. Kitade, and S.J. Senda Heterocyclic. Chem. 22 1985 345
21. M.J. Hartshorn, M.L. Verdonk, G. Chessari, S.C. Brewerton, W.T. Mooij, P.N. Mortenson, and C.W. Murray J. Med. Chem. 50 2007 726
22. O. Korb, T. Stützle, and T.E. Exner J. Chem. Inf. Model. 49 2009 84
23. Devkota, A. K.; Edupuganti, R.; Yan, C.; Shi, Y.; Jose, J.; Wang, Q.; Kaoud, T. S.; Cho, E. J.; Ren, P.; Dalby, K. N. manuscript in preparation.
24. C.D. Tavares, J.P. O'Brien, O. Abramczyk, A.K. Devkota, K.S. Shores, S.B. Ferguson, T.S. Kaoud, M. Warthaka, K.D. Marshall, K.M. Keller, Y. Zhang, J.S. Brodbelt, B. Ozpolat, and K.N. Dalby Biochemistry 51 2012 2232
25. O. Abramczyk, C.D. Tavares, A.K. Devkota, A.G. Ryazanov, B.E. Turk, A.F. Riggs, B. Ozpolat, and K.N. Dalby Protein Expr. Purif. 79 2011 237
26. C.G. Proud, X. Wang, J.V. Patel, L.E. Campbell, M. Kleijn, W. Li, and G.J. Browne Biochem. Soc. Trans. 29 2001 541
27. G.J. Browne, S.G. Finn, and C.G. Proud J. Biol. Chem. 279 2004 12220