Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

European Journal of Medicinal Chemistry

Volumn 61, Issue , 2013, Pages 61-72

  Zatloukal, Marek ^a   Jorda, Radek ^a   Gucký, Tomáš ^a   Řezníčková, Eva ^a   Voller, Jiří ^a   Pospíšil, Tomáš ^a   Malínková, Veronika ^a   Adamcová, Helena ^b   Kryštof, Vladimír ^a   Strnad, Miroslav ^a  

^a PALACKÝ UNIVERSITY   (Czech Republic)

^b BioPatterns Sro   (Czech Republic)

Author keywords

Apoptosis; Cancer; Cell cycle; Cyclin dependent kinase; Inhibitor; Roscovitine

Indexed keywords

(2 AMINOBENZYL) (2 CHLORO 9 ISOPROPYL 9H PURIN 6 YL) AMINE; (2 CHLORO 9 ISOPROPYL 9H PURIN 6 YL) (2,3 DIMETHOXYBENZYL) AMINE; (2 CHLORO 9 ISOPROPYL 9H PURIN 6 YL) (4 METHOXYBENZYL) AMINE; (4 AMINOBENZYL) (2 CHLORO 9 ISOPROPYL 9H PURIN 6 YL) AMINE; 2 [(2 CHLORO 9 ISOPROPYL 9H PURIN 6 YLAMINO) METHYL] 4 FLUOROPHENOL; 2 [(2 CHLORO 9 ISOPROPYL 9H PURIN 6 YLAMINO) METHYL] 6 METHOXYPHENOL; 2 [(2 CHLORO 9 ISOPROPYL 9H PURIN 6 YLAMINO) METHYL] PHENOL; 2,6 DICHLORO 9 ISOPROPYLPURINE; 4 [(2 CHLORO 9 ISOPROPYL 9H PURIN 6 YLAMINO) METHYL] PHENOL; 4 CHLORO 2 [(2 CHLORO 9 ISOPROPYL 9H PURIN 6 YLAMINO) METHYL] PHENOL; CYCLIN DEPENDENT KINASE; PROTEIN P53; ROSCOVITINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BIOCHEMISTRY; CANCER CELL CULTURE; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CONTROLLED STUDY; CORRELATION ANALYSIS; CYTOTOXICITY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; TRANSCRIPTION REGULATION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; HCT116 CELLS; HUMANS; K562 CELLS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PURINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84874934512     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.06.036     Document Type: Article

References (40)

1. M. Malumbres, and M. Barbacid Cell cycle, CDKs and cancer: a changing paradigm Nat. Rev. Cancer 9 2009 153 166
2. V. Krystof, and S. Uldrijan Cyclin-dependent kinase inhibitors as anticancer drugs Curr. Drug Targets 11 2010 291 302
3. C. Berthet, E. Aleem, V. Coppola, L. Tessarollo, and P. Kaldis Cdk2 knockout mice are viable Curr. Biol. 13 2003 1775 1785
4. M. Malumbres, R. Sotillo, D. Santamaria, J. Galan, A. Cerezo, S. Ortega, P. Dubus, and M. Barbacid Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6 Cell 118 2004 493 504
5. S. Ortega, M. Malumbres, and M. Barbacid Cyclin D-dependent kinases, INK4 inhibitors and cancer Biochim. Biophys. Acta 1602 2002 73 87
6. D. Santamaria, C. Barriere, A. Cerqueira, S. Hunt, C. Tardy, K. Newton, J.F. Caceres, P. Dubus, M. Malumbres, and M. Barbacid Cdk1 is sufficient to drive the mammalian cell cycle Nature 448 2007 811 815
7. L. Havlicek, J. Hanus, J. Vesely, S. LeClerc, L. Meijer, G. Shaw, and M. Strnad Cytokinin-derived cyclin-dependent kinase inhibitors: synthesis and cdc2 inhibitory activity of olomoucine and related compounds J. Med. Chem. 40 1997 408 412
8. S.J. McClue, D. Blake, R. Clarke, A. Cowan, L. Cummings, P.M. Fischer, M. MacKenzie, J. Melville, K. Stewart, S. Wang, N. Zhelev, D. Zheleva, and D.P. Lane In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine) Int. J. Cancer 102 2002 463 468
9. D.E. MacCallum, J. Melville, S. Frame, K. Watt, S. Anderson, A. Gianella-Borradori, D.P. Lane, and S.R. Green Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1 Cancer Res. 65 2005 5399 5407
10. S.R. Whittaker, R.H. Te Poele, F. Chan, S. Linardopoulos, M.I. Walton, M.D. Garrett, and P. Workman The cyclin-dependent kinase inhibitor seliciclib (R-roscovitine; CYC202) decreases the expression of mitotic control genes and prevents entry into mitosis Cell Cycle 6 2007 3114 3131
11. W.S. Hsieh, R. Soo, B.K. Peh, T. Loh, D. Dong, D. Soh, L.S. Wong, S. Green, J. Chiao, C.Y. Cui, Y.F. Lai, S.C. Lee, B. Mow, R. Soong, M. Salto-Tellez, and B.C. Goh Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer Clin. Cancer Res. 15 2009 1435 1442
12. T.C. Le, S. Faivre, V. Laurence, C. Delbaldo, K. Vera, V. Girre, J. Chiao, S. Armour, S. Frame, S.R. Green, A. Gianella-Borradori, V. Dieras, and E. Raymond Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies Eur. J. Cancer 46 2010 3243 3250
13. D. Mahadevan, R. Plummer, M.S. Squires, D. Rensvold, S. Kurtin, C. Pretzinger, T. Dragovich, J. Adams, V. Lock, D.M. Smith, H.D. Von, and H. Calvert A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors Ann. Oncol. 22 2011 2137 2143
14. D. Parry, T. Guzi, F. Shanahan, N. Davis, D. Prabhavalkar, D. Wiswell, W. Seghezzi, K. Paruch, M.P. Dwyer, R. Doll, A. Nomeir, W. Windsor, T. Fischmann, Y. Wang, M. Oft, T. Chen, P. Kirschmeier, and E.M. Lees Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor Mol. Cancer Ther. 9 2010 2344 2353
15. S.J. McClue, and I. Stuart Metabolism of the trisubstituted purine cyclin-dependent kinase inhibitor seliciclib (R-roscovitine) in vitro and in vivo Drug Metab. Dispos. 36 2008 561 570
16. B.P. Nutley, F.I. Raynaud, S.C. Wilson, P.M. Fischer, A. Hayes, P.M. Goddard, S.J. McClue, M. Jarman, D.P. Lane, and P. Workman Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse Mol. Cancer Ther. 4 2005 125 139
17. S.C. Wilson, B. Atrash, C. Barlow, S. Eccles, P.M. Fischer, A. Hayes, L. Kelland, W. Jackson, M. Jarman, A. Mirza, J. Moreno, B.P. Nutley, F.I. Raynaud, P. Sheldrake, M. Walton, R. Westwood, S. Whittaker, P. Workman, and E. McDonald Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors Bioorg. Med. Chem. 19 2011 6949 6965
18. N.J. Lalak, and D.L. Morris Azithromycin clinical pharmacokinetics Clin. Pharmacokinet. 25 1993 370 374
19. P.A. Meredith, and H.L. Elliott Clinical pharmacokinetics of amlodipine Clin. Pharmacokinet. 22 1992 22 31
20. R.J. O'Brien, M.A. Lyle, and D.E. Snider Jr. Rifabutin (ansamycin LM 427): a new rifamycin-S derivative for the treatment of mycobacterial diseases Rev. Infect. Dis. 9 1987 519 530
21. W. Lu, S. Sengupta, J.L. Petersen, N.G. Akhmedov, and X. Shi Mitsunobu coupling of nucleobases and alcohols: an efficient, practical synthesis for novel nonsugar carbon nucleosides J. Org. Chem. 72 2007 5012 5015
22. P. Imbach, H.G. Capraro, P. Furet, H. Mett, T. Meyer, and J. Zimmermann 2,6,9-Trisubstituted purines: optimization towards highly potent and selective CDK1 inhibitors Bioorg. Med. Chem. Lett. 9 1999 91 96
23. M. Otyepka, V. Krystof, L. Havlicek, V. Siglerova, M. Strnad, and J. Koca Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2 J. Med. Chem. 43 2000 2506 2513
24. M. Rypka, J. Vesely, Z. Chmela, D. Riegrova, K. Cervenkova, L. Havlicek, K. Lemr, J. Hanus, B. Cerny, J. Lukes, and K. Michalikova In vitro biotransformation of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine by mouse liver microsomes Xenobiotica 32 2002 1017 1031
25. V. Krystof, R. Lenobel, L. Havlicek, M. Kuzma, and M. Strnad Synthesis and biological activity of olomoucine II Bioorg. Med. Chem. Lett. 12 2002 3283 3286
26. M. Legraverend, O. Ludwig, E. Bisagni, S. LeClerc, L. Meijer, N. Giocanti, R. Sadri, and V. Favaudon Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors Bioorg. Med. Chem. 7 1999 1281 1293
27. Y.T. Chang, N.S. Gray, G.R. Rosania, D.P. Sutherlin, S. Kwon, T.C. Norman, R. Sarohia, M. Leost, L. Meijer, and P.G. Schultz Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors Chem. Biol. 6 1999 361 375
28. S.R. Schow, R.L. Mackman, C.L. Blum, E. Brooks, A.G. Horsma, A. Joly, S.S. Kerwar, G. Lee, D. Shiffman, M.G. Nelson, X.B. Wang, M.M. Wick, X.M. Zhang, and R.T. Lum Synthesis and activity of 2,6,9-trisubstituted purines Bioorg. Med. Chem. Lett. 7 1997 2697 2702
29. R. Jorda, L. Havlicek, I.W. McNae, M.D. Walkinshaw, J. Voller, A. Sturc, J. Navratilova, M. Kuzma, M. Mistrik, J. Bartek, M. Strnad, and V. Krystof Pyrazolo[4,3-d]pyrimidine bioisostere of roscovitine: evaluation of a novel selective inhibitor of cyclin-dependent kinases with antiproliferative activity J. Med. Chem. 54 2011 2980 2993
30. V. Krystof, I.W. McNae, M.D. Walkinshaw, P.M. Fischer, P. Muller, B. Vojtesek, M. Orsag, L. Havlicek, and M. Strnad Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor Cell Mol. Life Sci. 62 2005 1763 1771
31. J. Vesely, L. Havlicek, M. Strnad, J.J. Blow, A. Donella-Deana, L. Pinna, D.S. Letham, J. Kato, L. Detivaud, and S. LeClerc Inhibition of cyclin-dependent kinases by purine analogues Eur. J. Biochem. 224 1994 771 786
32. K. Vermeulen, M. Strnad, V. Krystof, L. Havlicek, A. Van der Aa, M. Lenjou, G. Nijs, I. Rodrigus, B. Stockman, O.H. Van, D.R. Van Bockstaele, and Z.N. Berneman Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases Leukemia 16 2002 299 305
33. Z. Chmela, J. Vesely, K. Lemr, M. Rypka, J. Hanus, L. Havlicek, V. Krystof, L. Michnova, K. Fuksova, and J. Lukes In vivo metabolism of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine in mice: glucosidation as the principal metabolic route Drug Metab. Dispos. 29 2001 326 334
34. L. Havlicek, K. Fuksova, V. Krystof, M. Orsag, B. Vojtesek, and M. Strnad 8-Azapurines as new inhibitors of cyclin-dependent kinases Bioorg. Med. Chem. 13 2005 5399 5407
35. S. Wang, G. Griffiths, C.A. Midgley, A.L. Barnett, M. Cooper, J. Grabarek, L. Ingram, W. Jackson, G. Kontopidis, S.J. McClue, C. McInnes, J. McLachlan, Ch. Meades, M. Mezna, I. Stuart, M.P. Thomas, D.I. Zheleva, D.P. Lane, R.C. Jackson, D.M. Glover, D.G. Blake, and P.M. Fischer Discovery and characterization of 2-anilino-4-(thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents Chem. Biol. 17 2010 1111 1121
36. V. Krystof, D. Moravcova, M. Paprskarova, P. Barbier, V. Peyrot, A. Hlobilkova, L. Havlicek, and M. Strnad Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin Eur. J. Med. Chem. 41 2006 1405 1411
37. M. Paprskarova, V. Krystof, R. Jorda, P. Dzubak, M. Hajduch, J. Wesierska-Gadek, and M. Strnad Functional p53 in cells contributes to the anticancer effect of the cyclin-dependent kinase inhibitor roscovitine J. Cell Biochem. 107 2009 428 437
38. V. Krystof, I. Chamrad, R. Jorda, and J. Kohoutek Pharmacological targeting of CDK9 in cardiac hypertrophy Med. Res. Rev. 30 2010 646 666
39. R.A. Robinson, and A.K. King Trans. Faraday Soc. 52 1955 327 330
40. P.M. Fischer, M. Jarman, E. McDonald, B. Nutley, F. Raynaud, S. Wilson, P. Workman, UK Patent Application, GB 2392155 A, 2004.