Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition

Journal of Medicinal Chemistry

Volumn 48, Issue 8, 2005, Pages 3080-3084

  Fancelli, Daniele ^a   Berta, Daniela ^a   Bindi, Simona ^a   Cameron, Alexander ^a   Cappella, Paolo ^a   Carpinelli, Patrizia ^a   Catana, Cornel ^a,b   Forte, Barbara ^a   Giordano, Patrizia ^a   Giorgini, Maria Laura ^a   Mantegani, Sergio ^a   Marsiglio, Aurelio ^a   Meroni, Maurizio ^a   Moll, Juergen ^a   Pittalà, Valeria ^a,c   Roletto, Fulvia ^a   Severino, Dino ^a   Soncini, Chiara ^a   Storici, Paola ^a   Tonani, Roberto ^a   Varasi, Mario ^a   Vulpetti, Anna ^a   Vianello, Paola ^a   more..

^a NERVIANO MEDICAL SCIENCES   (Italy)

^b PFIZER INC   (United States)

^c UNIVERSITY OF CATANIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,4,5,6 TETRAHYDROPYRROLO[3,4 C]PYRAZOLE; ADENOSINE TRIPHOSPHATE; AURORA KINASE INHIBITOR PROTEIN; AURORA KINASE PROTEIN; BICYCLO COMPOUND; PROTEIN; PROTEIN KINASE; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; TUMOR CELL LINE;

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENTS; BICYCLO COMPOUNDS, HETEROCYCLIC; BINDING SITES; CELL LINE; CELL LINE, TUMOR; CELL PROLIFERATION; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MODELS, MOLECULAR; PIPERAZINES; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 20944437351     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049076m     Document Type: Article

References (15)

1. Meraldi, P.; Honda, R.; Nigg, E. A. Aurora kinases link chromosome segregation and cell division to cancer susceptibility. Curr. Opin. Genet., Dev. 2004, 14(1), 29-36.
2. Warner, S. L.; Bearss, D. J.; Han, H.; Von Hoff, D. D. Targeting Aurora-2 kinase in cancer. Mol. Cancer Ther. 2003, 2(6), 589-595.
3. Doggrell, S. A. Dawn of Aurora kinase inhibitors as anticancer drugs. Expert Opin. Investig. Drugs 2004, 13(9), 1199-1201.
4. Sasai, K.; Katayama, H.; Stenoien, D. L.; Fujii, S.; Honda, R.; Kimura, M.; Okano, Y.; Tatsuka, M.; Suzuki, F.; Nigg, E. A.; Earnshaw, W. C.; Brinkley, W. R.; Sen, S. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil. Cytoskeleton 2004, 59, 249-263.
5. Bischoff, J. R.; Anderson, L.; Zhu, Y.; Mossie, K.; Ng, L.; Souza, B.; Schryver, B.; Flanagan, P.; Clairvoyant, F.; Ginther, C.; Chan, C. S.; Novotny, M.; Slamon, D. J.; Plowman, G. D. A homolog of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998, 17(11), 3052-3065.
6. Warner, S. L.; Bearss, D. J.; Han, H.; Von Hoff, D.D.; Targeting Aurora-2 kinase in cancer. Mol Cancer Ther. 2003, 2(6), 589-95.
7. Ditchfield, C.; Johnson, V. L.; Tighe, A.; Elision, R.; Haworth, C.; Johnson, T.; Mortlock, A.; Keen, N.; Taylor, S. S.; Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J. Cell Biol. 2003, 161(2), 267-280.
8. Harrington, E. A.; Bebbington, D.; Moore, J.; Rasmussen, R. K.; Ajose-Adeogun, A. O.; Nakayama, T.; Graham, J. A.; Demur, C.; Hercend, T.; Diu-Hercend, A.; Su, M.; Golec, J. M. C.; Miller, K. M. X-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med. 2004, 10(3), 262-327.
9. Tang, J.; Shewchuk, L. M.; Sato, H.; Hasegawa, M.; Washio, Y.; Nishigaki, N Anilinopyrazole as selective CDK2 inhibitors: design, synthesis, biological evaluation, and X-ray crystallographic analysis. Bioorg., Med. Chem. Lett. 2003, 13(18), 2985-2988.
10. Pevarello, P.; Brasca, G. M.; Amici, R.; Orsini, P.; Traquandi, G.; Corti, L.; Piutti, C.; Sansonna, P.; Villa, M.; Pierce, B. S.; Pulici, M.; Giordano, P.; Martina, K.; Fritzen, E. L.; Nugent, R. A.; Casale, E.; Cameron, A.; Ciomei, M.; Roletto, F.; Isacchi, A.; Fogliatto, G.; Pesenti, E.; Pastori, W; Marsiglio, A.; Leach, K. L.; Clare, P. M.; Fiorentini, F.; Varasi, M.; Vulpetti, A.; Warpehoski, M. A. 3-Aminopyrazole Inhibitors of CDK2/Cyclin A as Antitumor Agents. 1. Lead Finding. J. Med. Chem. 2004, 47(13), 3367-3380.
11. Regan, J.; Capolino, A.; Cirillo, P. F.; Gilmore, T.; Graham, A. G.; Hickey, E.; Kroe, R. R.; Madwed, J.; Moriak, M.; Nelson, R.; Pargellis, C. A.; Swinamer, A.; Torcellini, C.; Tsang, M.; Moss, N. Structure-Activity Relationships of the p38 MAP Kinase Inhibitor 1-(5-terf-Butyl-2-p-tolyl-2H- pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]urea. J. Med. Chem. 2003, 46(13), 4676-4686.
12. Vulpetti, A.; Bosotti, R. Sequence and Structural Analysis of Kinase ATP Pocket Residues. Il Farmaco, in press.
13. Gadekar, S. M.; Johnson, B. D.; Cohen, E. Dihydropyrrolo[3,4-c]pyrazoles. J. Med. Chem. 1968, 11(3), 616-618.
14. Fancelli, D.; Pittala, V.; Varasi, M. Combinatorial preparation of bicyclo pyrazoles as kinase inhibitors for treatment of cancer and other proliferative disorders. WO 02/012242, 2000.
15. Bayliss, R.; Sardon, T.; Vernos, I.; Conti, E.; Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol. Cell 2003, 12(4), 851-862.