Cyclin-dependent kinase inhibition by new C-2 alkynylated purine derivatives and molecular structure of a CDK2-inhibitor complex

Journal of Medicinal Chemistry

Volumn 43, Issue 7, 2000, Pages 1282-1292

  Legraverend, Michel ^a   Tunnah, Paul ^c   Noble, Martin ^c   Ducrot, Pierre ^a   Ludwig, Odile ^a   Grierson, David S ^a   Leost, Maryse ^b   Meijer, Laurent ^b   Endicott, Jane ^c  

^a INSTITUT CURIE   (France)

^b STATION BIOLOGIQUE   (France)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 [6 (3,4 DICHLOROPHENYLAMINO) 9 ISOPROPYL 9H PURIN 2 YL] 3 METHYLPENT 1YN 3 OL; 1 [6 (4 CHLOROBENZYLAMINO) 9 ISOPROPYL 9H PURIN 2 YL] 3 METHYLPENT 1 YN 3 OL; 1 [9 ISOPROPYL 6 (4 METHOXYBENZYLAMINO) 9H PURIN 2 YL] 3 METHYLPENT 1 YN 3 OL; CYCLIN DEPENDENT KINASE; FLAVOPIRIDOL; INDIRUBINE 3' MONOXIME; KENPAULLONE; OL 567; OLOMOUCINE; PURINE DERIVATIVE; PURVALANOL A; PURVALANOL B; ROSCOVITINE; STAUROSPORINE; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME INHIBITOR COMPLEX; MOLECULAR MODEL; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ADENINE; CDC2 PROTEIN KINASE; CDC2-CDC28 KINASES; CRYSTALLOGRAPHY, X-RAY; CYCLIN B; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASES; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN-SERINE-THREONINE KINASES; PURINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034611620     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9911130     Document Type: Article

References (46)

1. Keyomarsi, K.; Grana, X. In Progress in Cell Cycle Research; Meijer, L. G., Philippe, M., Eds.; Plenum Press: New York, 1997; pp 171-191.
2. Morgan, D. O. Principles of CDK regulation. Nature 1995, 374, 131-134.
3. WAF1. Curr. Biol. 1996, 7, 71-80.
4. Kip1. Cell 1996, 85, 721-732.
5. Hui, A. M.; Sun, L.; Kanai, Y.; Sakamoto, M.; Hirohashi, S. Reduced p27(Kip1) expression in hepatocellular carcinomas. Cancer Lett. 1998, 132, 67-73.
6. Hanks, S. K.; Quinn, A.-M.; Hunter, T. The protein kinase family: Conserved features and deduced phylogeny of the catalytic domains. Science 1988, 241, 42-52.
7. Taylor, S. S.; Radzio-Andzelm, E. Three protein kinase structures define a common motif. Structure 1994, 2, 345-355.
8. Veseley, J.; Havlicek, L.; Strnad, M.; Blow, J. J.; Donella-Deana, A.; Pinna, L.; Letham, D. S.; Kato, J.-Y.; Detivaud, L.; Leclerc, S.; Meijer, L. Inhibition of cyclin-dependent kinases by purine analogues. Eur. J. Biochem. 1994, 224, 771-786.
9. Meijer, L.; Borgne, A.; Mulner, O.; Chong, J. P. J.; Blow, J. J.; Inagaki, N.; Inagaki, M.; Delcros, J. G.; Moulinoux, J. P. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 1997, 243, 527-536.
10. Imbach, P.; Capraro, H. G.; Furet, P.; Mett, H.; Meyer, T.; Zimmermann, J. 2,6,9-trisubstituted purines: Optimization towards highly potent and selective CDK1 inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 91-96.
11. Gray, N. S.; Wodicka, L.; Thunnissen, A. M. W. H.; Norman, T. C.; Kwon, S. J.; Espinoza, F. H.; Morgan, D. O.; Barnes, G.; LeClerc, S.; Meijer, L.; Kim, S. H.; Lockhart, D. J.; Schultz, P. G. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 1998, 281, 533-538.
12. Chang, Y. T.; Gray, N. S.; Rosania, G. R.; Sutherlin, D. P.; Kwon, S.; Norman, T. C.; Sarohia, R.; Leost, M.; Meijer, L.; Schultz, P. G. Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chem. Biol. 1999, 6, 361-375.
13. De Azevedo, W. F.; Mueller-Dieckmann, H.-J.; Schulze-Gahmen, U.; Worland, P. J.; Sausville, E.; Kim, S.-H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 2735-2740.
14. Hoessel, R.; Leclerc, S.; Endicott, J.; Noble, M.; Lawrie, A.; Tunnah, P.; Leost, M.; Damiens, E.; Marie, D.; Marko, D.; Niederberger, E.; Tang, W.; Eisenbrand, G.; Meijer, L. Indirubin, the active constituent of a chinese antileukeamia medicine, inhibits cyclin-dependent kinases. Nature Cell Biol. 1999, 1, 60-67.
15. Schultz, C.; Link, A.; Leost, M.; Zaharevitz, D. W.; Gussio, R.; Sausville, E. A.; Meijer, L.; Kunick, C. Paullones, a series of cyclin-dependent kinase inhibitors: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity. J. Med. Chem. 1999, 42, 2909-2919.
16. Legraverend, M.; Ludwig, O.; Bisagni, E.; Leclerc, S.; Meijer, L. Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. Lett. 1998, 8, 793-798.
17. De Bondt, H. L.; Rosenblatt, J.; Jancarik, J.; Jones, H. D.; Morgan, D. O.; Kim, S.-H. Crystal structure of cyclin-dependent kinase 2. Nature 1993, 363, 595-602.
18. Schulze-Gahmen, U.; Brandsen, J.; Jones, H. D.; Morgan, D. O.; Meijer, L.; Vesely, J.; Kim, S.-H. Multiple modes of ligand recognition: Crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine. Proteins Struct. Funct. Genet. 1995, 22, 378-391.
19. De Azevedo, W. F.; Leclerc, S.; Meijer, L.; Havlicek, L.; Strnad, M.; Kim, S. H. Inhibition of cyclin-dependent kinases by purine analogues - Crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem. 1997, 243, 518-526.
20. Lawrie, A. M.; Noble, M. E. M.; Tunnah, P.; Brown, N. R.; Johnson, L. N.; Endicott, J. A. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nature Struct. Biol. 1997, 4, 796-801.
21. Jeffrey, P. D.; Russo, A. A.; Polyak, K.; Gibbs, E.; Hurwitz, J.; Massagué, J.; Pavletich, N. P. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 1995, 376, 313-320.
22. Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 1996, 382, 325-331.
23. Legraverend, M.; Boumchita, H.; Zerial, A.; Huel, C.; Lemaitre, M.; Bisagni, E. Synthesis of new (±)-3,5-dihydroxypentyl nucleoside analogues from 1-amino-5-(benzyloxy)pentan-3-ol and their antiviral evaluation. J. Med. Chem. 1990, 33, 2476-2480.
24. Legraverend, M.; Boumchita, H.; Bisagni, E. A new route to 2,5-diamino-4,6-dichloropyrimidine, a key precursor of 9-substituted guanines. Synthesis 1990, 587-590.
25. Legraverend, M.; Ludwig, O.; Bisagni, E.; Leclerc, S.; Meijer, L.; Giocanti, N.; Sadri, R.; Favaudon, V. Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines as cyclin-dependent kinases inhibitors. Bioorg. Med. Chem. 1999, 7, 1281-1293.
26. Sonogashira, K.; Tohda, Y.; Hagihara, N. A convenient synthesis of acetylenes: Catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes, and bromopyridines. Tetrahedron Lett. 1975, 4467-4470.
27. Sharma, P.; Steinbach, P. J.; Sharma, M.; Amin, N. D.; Barchi, J. J.; Pant, H. C. Identification of substrate binding site of cyclin-dependent kinase 5. J. Biol. Chem. 1999, 274, 9600-9606.
28. Chou, K. C.; Watenpaugh, K. D.; Heinrikson, R. L. A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator. Biochem. Biophys. Res. Commun. 1999, 259, 420-428.
29. Norman, T. C.; Gray, N. S.; Hoh, J. T.; Schultz, P. G. A structure-based library approach to kinase inhibitors. J. Am. Chem. Soc. 1996, 118, 7430-7431.
30. Schow, S. R.; Mackman, R. L.; Blum, C. L.; Brooks, E.; Horsma, A. G.; Joly, A.; Kerwar, S. S.; Lee, G.; Shiffman, D.; Nelson, M. G.; Wang, X.; Wick, M. M.; Zhang, X.; Lum, R. T. Synthesis and activity of 2,6,9-trisubstituted purines. Bioorg. Med. Chem. Lett. 1997, 7, 2697-2702.
31. Zimmerman, J.; Capraro, H. G.; Peterli, P.; Furet, P. Purine derivatives and processes for their preparation. Patent WO 97/ 16452, 1997.
32. Meijer, L.; Kim, S. H. Chemical inhibitors of cyclin-dependent kinases. Methods Enzymol. 1997, 283, 113-128.
33. Brown, N. R.; Noble, M. E. M.; Lawrie, A. M.; Morris, M. C.; Tunnah, P.; Divita, G.; Johnson, L. N.; Endicott, J. A. Effects of phosphorylation ofthreonine 160 on cyclin-dependent kinase 2 structure and activity. J. Biol. Chem. 1999, 274, 8746-8756.
34. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995, 8, 127-134.
35. Rosenblatt, J.; DeBondt, H.; Jancarik, J.; Morgan, D. O.; Kim, S. H. Purification and crystallisation of human cyclin-dependent kinase 2. J. Mol. Biol. 1993, 230, 1317-1319.
36. Schulze-Gahmen, U.; De Bondt, H. L.; Kim, S.-H. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: Bound waters and natural ligand for inhibitor design. J. Med. Chem. 1996, 39, 4540-4546.
37. Russo, A.; Jeffrey, P. D.; Pavletich, N. P. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nature Struct. Biol. 1996, 3, 696-700.
38. Nishio, M.; Hirota, M. CH/π interaction: Implications in organic chemistry. Tetrahedron 1989, 45, 7201-7245.
39. Brotherton, D. H.; Dhanaraj, V.; Wick, S.; Brizuela, L.; Domaille, P. J.; Volyanik, E.; Xu, X.; Parisini, E.; Smith, B. O.; Archer, S. J.; Serrano, M.; Brenner, S. L.; Blundell, T. L.; Laue, E. D. Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 1998, 395, 244-250.
40. Meyerson, M.; Enders, G. H.; Wu, C.-L.; Su, L.-K.; Gorka, C.; Nelson, C.; Harlow, E.; Tsai, L.-H. A family of human cdc2-related protein kinases. EMBO J. 1992, 11, 2909-2917.
41. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997, 276, 307-326.
42. Calvert, A. H. Unpublished results.
43. Sybyl, 6.3 ed.; SYBYL Molecular Modeling Software, Tripos Associates Ltd.: St. Louis, MO, 1992.
44. Jones, T. A.; Zou, J. Y.; Cowan, S. W.; Kjeldgaard, M. Improved method for building models in electron density maps and the location of errors in these models. Acta Crystallogr. 1991, A47, 110-119.
45. Murshudov, G. N.; Vagen, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum -likelihood method. Acta Crystallogr. 1997, D53, 240-255.
46. Lamzin, V. S.; Wilson, K. S. Automated refinement of protein models. Acta Crystallogr. 1993, D49, 129-147.