Imidazo[4,5-b]pyridine derivatives as inhibitors of aurora kinases: Lead optimization studies toward the identification of an orally bioavailable preclinical development candidate

Journal of Medicinal Chemistry

Volumn 53, Issue 14, 2010, Pages 5213-5228

  Bavetsias, Vassilios ^a   Large, Jonathan M ^a   Sun, Chongbo ^a   Bouloc, Nathalie ^a   Kosmopoulou, Magda ^a   Matteucci, Mizio ^a   Wilsher, Nicola E ^a   Martins, Vanessa ^a   Reynisson, Jóhannes ^a   Atrash, Butrus ^a   Faisal, Amir ^a   Urban, Frederique ^a   Valenti, Melanie ^a   De Haven Brandon, Alexis ^a   Box, Gary ^a   Raynaud, Florence I ^a   Workman, Paul ^a   Eccles, Suzanne A ^a   Bayliss, Richard ^a   Blagg, Julian ^a   Linardopoulos, Spiros ^a   McDonald, Edward ^a   more..

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 [[4 [6 BROMO 2 [4 (4 METHYLPIPERAZIN 1 YL)PHENYL] 3H IMIDAZO[4,5 B]PYRIDIN 7 YL]PIPERAZIN 1 YL]METHYL] 5 METHYLISOXAZOLE; AURORA KINASE INHIBITOR; CCT 137444; CCT 137690; IMIDAZO[4,5 B]PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOAVAILABILITY; COLON CARCINOMA; CONTROLLED STUDY; CRYSTALLIZATION; DRUG ACTIVITY; DRUG EFFICACY; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; TUMOR XENOGRAFT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; BLOOD PROTEINS; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; ETHER-A-GO-GO POTASSIUM CHANNELS; FEMALE; HUMANS; IMIDAZOLES; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MICROSOMES, LIVER; MODELS, MOLECULAR; NEOPLASM TRANSPLANTATION; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS;

EID: 77954715614     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100262j     Document Type: Article

References (42)

1. Carmena, M; Earnshaw, W. C. The Cellular Geography of Aurora Kinases Nat. Rev. Mol. Cell Biol. 2003, 4, 842-854
2. Ducat, D.; Zheng, Y. Aurora Kinases in Spindle Assembly and Chromosome Segregation Exp. Cell Res. 2004, 301, 60-67
3. Marumoto, T.; Zhang, D.; Saya, H. Aurora-A, A Guardian of Poles Nat. Rev. Cancer 2005, 5, 42-50
4. Bishop, J. D.; Schumacher, J. M. Phosphorylation of the Carboxyl Terminus of Inner Centromere Protein (INCENP) by Aurora B Kinase Stimulates Aurora B Kinase Activity J. Biol. Chem. 2002, 277, 27577-27580
5. Giet, R.; Glover, D. M. Drosophila Aurora B Kinase Is Required for Histone H3 Phosphorylation and Condensin Recruitment During Chromosome Condensation and to Organise the Central Spindle During Cytokinesis J. Cell Biol. 2001, 152, 669-682
6. Keen, N.; Taylor, S. Aurora-Kinase Inhibitors as Anticancer Agents Nat. Rev. Cancer 2004, 4, 927-936
7. Matthews, N.; Visintin, C.; Hartzoulakis, B.; Jarvis, A.; Selwood, D. L. Aurora A and B Kinases As Targets for Cancer: Will They be Selective For Tumors? Exp. Rev. Anticancer Ther. 2006, 6, 109-120
8. Gautschi, O.; Heighway, J.; Mack, P. C.; Purnell, P. R.; Lara, P. N., Jr.; Gandara, D. R. Aurora Kinases as Anticancer Drug Targets Clin. Cancer Res. 2008, 14, 1639-1648
9. Tanaka, T.; Kimura, M.; Matsunaga, K.; Fukada, D.; Mori, H.; Okano, Y. Centrosomal Kinase AIK1 is Overexpressed in Invasive Ductal Carcinoma of the Breast Cancer Res. 1999, 59, 2041-2044
10. Bischoff, J. R.; Anderson, L.; Zhu, Y.; Mossie, K.; Ng, L.; Souza, B.; Schryver, B.; Flanagan, P.; Clairvoyant, F.; Ginther, C.; Chan, C. S. M.; Novotny, M.; Slamon, D. J.; Plowman, G. D. A Homologue of Drosophila Aurora Kinase Is Oncogenic and Amplified in Human Colorectal Cancers EMBO J. 1998, 17, 3052-3065
11. Gritsko, T. M.; Coppola, D.; Paciga, J. E.; Yang, L.; Sun, M.; Shelley, S. A.; Fiorica, J. V.; Nicosia, S. V.; Cheng, J. Q. Activation and Overexpression of Centrosome Kinase BTAK/Aurora-A in Human Ovarian Cancer Clin. Cancer. Res. 2003, 9, 1420-1426
12. Reichardt, W.; Jung, V.; Brunner, C.; Klein, A.; Wemmert, S.; Romeike, B. F. M.; Zang, K. D.; Urbschat, S. The Putative Serine/Threonine Kinase Gene STK15 on Chromosome 20q13.2 Is Amplified in Human Gliomas Oncol. Rep. 2003, 10, 1275-1279
13. Zhou, H.; Kuang, J.; Zhong, L.; Kuo, W.; Gray, J. W.; Sahin, A.; Brinkley, B. R.; Sen, S. Tumour Amplified Kinase ST15/BTAK Induces Centrosome Amplification, Aneuploidy, and Transformation Nat. Genet. 1998, 20, 189-193
14. Chieffi, P.; Troncone, G.; Caleo, A.; Libertini, S.; Linardopoulos, S.; Tramontano, D.; Portella, G. Aurora B Expression in Normal Testis and Seminonas J. Endocrinol. 2004, 181, 263-270
15. Araki, K.; Nozaki, K.; Ueba, T.; Tatsuka, M.; Hashimoto, N. High Expression of Aurora-B/Aurora and Ipl1I-like Midbody-Associated Protein (AIM-1) in Astrocytomas J. Neurooncol. 2004, 67, 53-64
16. Sorrentino, R.; Libertini, S.; Pallante, P. L.; Troncone, G.; Palombini, L.; Bavetsias, V.; Cernia, D. S.; Laccetti, P.; Linardopoulos, S.; Chieffi, P.; Fusco, A.; Portella, G. Aurora B Overexpression Associates with the Thyroid Carcinoma Undifferentiated Phenotype and Is Required for Thyroid Carcinoma Cell Proliferation J. Clin. Endocrinol. Metab. 2005, 90, 928-935
17. Ota, T.; Suto, S.; Katayama, H.; Han, Z-B; Suzuki, F.; Maeda, M.; Tanino, M.; Terada, Y.; Tatsuka, M. Increased Mitotic Phosphorylation of Histone H3 Attributable to AIM-1/Aurora-B Overexpression Contributes to Chromosome Number Instability Cancer Res. 2002, 62, 5168-5177
18. Takahashi, T.; Futamura, M.; Yoshimi, N.; Sano, J.; Katada, M.; Takagi, Y.; Kimura, M.; Yoshioka, T.; Okano, Y.; Saji, S. Centrosomal Kinases, HsAIRK1 and HsAIRK3, Are Overexpressed in Primary Colorectal Cancers Jpn. J. Cancer Res. 2000, 91, 1007-1014
19. Pollard, J. R.; Mortimore, M. Discovery and Development of Aurora Kinase Inhibitors As Anticancer Agents J. Med. Chem. 2009, 52, 2629-2651
20. 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. VX-680, a Potent and Selective Small-Molecule Inhibitor of the Aurora Kinases, Suppresses Tumor Growth in Vivo Nat. Med. 2004, 10, 262-267
21. Fancelli, D.; Moll, J.; Varasi, M.; Bravo, R.; Artico, R.; Berta, D.; Bindi, S.; Cameron, A.; Candiani, I.; Cappella, P.; Carpinelli, P.; Croci, W.; Forte, B.; Giorgini, M. L.; Klapwijk, J.; Marsiglio, A.; Pesenti, E.; Roccheti, M.; Roletto, F.; Severino, D.; Soncini, C.; Storici, P.; Tonani, R.; Zugnoni, P.; Vianello, P. 1,4,5,6-Tetrahydropyrrolo[3,4- c ]pyrazoles: Identification of a Potent Aurora Kinase Inhibitor With a Favorable Antitumor Kinase Inhibition Profile J. Med. Chem. 2006, 49, 7247-7251
22. Caprinelli., P.; Ceruti, R.; Giorgini, M. L.; Cappella, P.; Gianellini, L.; Croci, V.; Degrassi, A.; Texido, G.; Rocchetti, M.; Vianello, P.; Rusconi, L.; Storici, P.; Zugnoni, P.; Arrigoni, C.; Soncini, C.; Alli, C.; Patton, V.; Marsiglio, A.; Ballinari, D.; Pesenti, E.; Fancelli, D.; Moll, J. PHA-739358, a Potent Inhibitor of Aurora Kinases With a Selective Target Inhibition Profile Relevant to Cancer Mol. Cancer Ther. 2007, 6, 3158-3168
23. Howard, S.; Berdini, V.; Boulstridge, J. A.; Carr, M. G.; Cross, D. M.; Curry, J.; Devine, L. A.; Early, T. R.; Fazal, L.; Gill, A. L.; Heathcote, M.; Maman, S.; Matthews, J. E.; McMenamin, R. L.; Navarro, E. F.; O'Brien, M. A.; O'Reilly., M.; Rees, D. C.; Reule, M.; Tisi, D.; Williams, G.; Vinkovic, M; Wyatt, P. G. Fragment-Based Discovery of the Pyrazol-4-yl urea (AT9283), a Multitargeted Kinase Inhibitor With Potent Aurora Kinase Activity J. Med. Chem. 2009, 52, 379-388
24. Oslob, J. D.; Romanowski, M. J.; Allen, D. A.; Baskaran, S.; Bui, M.; Elling, R. A.; Flanagan, W. M.; Fung, A. D.; Hanan, E. J.; Harris, S.; Heumann, S. A.; Hoch, U.; Jacobs, J. W.; Lam, J.; Lawrence, C. E.; McDowell, R. S.; Nannini, M. A.; Shen, W.; Silverman, J. A.; Sopko, M. M.; Tangonan, B. T.; Teague, J.; Yoburn, J. C.; Yu, C. H.; Zhong, M.; Zimmerman, K. M.; O'Brien, T.; Lew, W. Discovery of a Potent and Selective Aurora Kinase Inhibitor Bioorg. Med. Chem. Lett. 2008, 18, 4880-4884
25. Manfredi, M. G.; Ecsedy, J. A.; Meetze, K. A.; Balani, S. K.; Burenkova, O.; Chen, W.; Galvin, K. M.; Hoar, K. M.; Huck, J. J.; LeRoy, P. J.; Ray, E. T.; Sells, T. B.; Stringer, B.; Stroud, S. G.; Vos, T. J.; Weatherhead, G. S.; Wysong, D. R.; Zhang, M.; Bolen, J. B.; Claiborne, C. F. Antitumour Activity of MLN8054, an Orally Active Small-Molecule Inhibitor of Aurora A Kinase Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 4106-4111
26. Mortlock, A. A.; Foote, K. M.; Heron, N. M.; Jung, F. H.; Pasquet, G.; Lohmann, J-J. M.; Warin, N.; Renaud, F.; De Savi, C.; Roberts, N. J.; Johnson, T.; Dousson, C. B.; Hill, G. B.; Perkins, D.; Hatter, G.; Wilkinson, R. W.; Wedge, S. R.; Heaton, S. P.; Odedra, R.; Keen, N. J.; Crafter, C.; Brown, E.; Thompson, K.; Brightwell, S.; Khatri, L.; Brady, M. C.; Kearney, S.; McKillop, D.; Rhead, S.; Parry, T.; Green, S. Discovery, Synthesis, and in Vivo Activity of a New Class of Pyrazoloquinazolines as Selective Inhibitors of Aurora B Kinase J. Med. Chem. 2007, 50, 2213-2224
27. Bavetsias, V.; Sun, C.; Bouloc, N.; Reynisson, J.; Workman, P.; Linardopoulos, S.; McDonald, E. Hit generation and exploration: Imidazo[4,5- b ]pyridine Derivatives as Inhibitors of Aurora Kinases Bioorg. Med. Chem. Lett. 2007, 17, 6567-6571
28. Chan, F.; Sun, C.; Perumal, M.; Nguyen, Q.-D.; Bavetsias, V.; McDonald, E.; Martins, V.; Wilsher, N.; Valenti, M.; Eccles, S.; te Poele, R.; Workman, P.; Aboagye, E. O.; Linardopoulos, S. Mechanism of Action And in Vivo Quantification of Biological Activity of the Aurora Kinase Inhibitor CCT129202 Mol. Cancer Ther. 2007, 6, 3147-3157
29. Yang, D.; Fokas, D.; Li, J.; Yu, L.; Baldino, C. M. A Versatile Method for the Synthesis of Benzimidazoles from o -Nitroanilines and Aldehydes in One Step via a Reductive Cyclization Synthesis 2005, 47-56
30. Gudmundsson, K. S.; Hinkley, J. M.; Brieger, M. S.; Drach, J. C.; Townsend, L. B. An Improved Large Scale Synthesis of 2-Amino-4-chloropyridine and Its Use for The Convenient Preparation of Various Polychlorinated 2-Aminopyridines Synth. Commun. 1997, 27, 861-870
31. Wallace, D. J.; Chen, C. Cyclopropylboronic Acid: Synthesis and Suzuki Cross-Coupling Reactions Tetrahedron Lett. 2002, 43, 6987-6990
32. Bellezza, F.; Cipiciani, A.; Cruciani, G.; Fringuelli, F. The Importance of Ester and Alkoxy Type Functionalities for the Chemo- and Enantio-Recognition of Substrates by Hydrolysis With Candida Rugosa Lipase J. Chem. Soc. Perkin 1 2000, 4439-4444
33. Tretyakova, A. V.; Rudaya, L. I.; Eltsov, A. V. Acid-base Properties of Isomeric 2-Arylimidazopyridines Zhurnal Obshchei Khimii 1984, 54, 2617-2620
34. Dalvie, D. K.; Kalgutkar, A. S.; Khojasteh-Bakht, S. C.; Obach, R. S.; O'Donnell, J. P. Biotransformation Reactions of Five-Membered Aromatic Heterocyclic Rings Chem. Res. Toxicol. 2002, 15, 269-298
35. Blagg, J. Structure-Activity Relationships for In Vitro and In Vivo Toxicity Annu. Rep. Med. Chem. 2006, 41, 353-369
36. Kalgutkar, A. S.; Dalvie, D. K.; O'Donnell, J. P.; Taylor, T. J.; Sahakian, D. C. On the Diversity of Oxidative Bioactivation Reactions on Nitrogen-Containing Xenobiotics Curr. Drug Metab. 2002, 3, 379-424
37. Nutley, B. P.; Smith, N. F.; Hayes, A.; Kelland, L. R.; Brunton, L.; Golding, B. T.; Smith, G. C.; Martin, N. M.; Workman, P.; Raynaud, F. I. Preclinical Pharmacokinetics and Metabolism of a Novel Prototype DNA-PK Inhibitor NU7026 Br. J. Cancer 2005, 93, 1011-1018
38. CLogP was calculated using ChemBioDraw 11.00 Ultra by CambridgeSoft (www.cambridgesoft.com).
39. Bayliss, R.; Sardon, T.; Vernos, I.; Conti, E. Structural Basis of Aurora-A Activation by TPX2 at the Mitotic Spindle Mol. Cell 2003, 12, 851-862
40. CCP4. The CCP4 (Collaborative Computational Project Number 4) Suite: Programmes for Protein Crystallography. Acta Crystallogr. D Biol. Crystallogr. 1994, 50, 760-763.
41. Adams, P. D.; Grosse-Kunstleve, R. W.; Hung, L. W.; Ioerger, T. R.; McCoy, A. J.; Moriarty, N. W.; Read, R. J.; Sacchettini, J. C.; Sauter, N. K.; Terwilliger, T. C. PHENIX: Building New Software for Automated Crystallographic Structure Determination Acta Crystallogr. D Biol. Crystallogr. 2002, 58, 1948-1954
42. Moreno-Farre, J.; Workman, P.; Raynaud, F. I. Analysis of Potential Drug-Drug Interactions for Anticancer Agents in Human Liver Microsomes by High Throughput Liquid Chromatography/Mass Spectrometry Assay Austral.-Asian J. Cancer 2007, 6, 55-68