Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors

Journal of Medicinal Chemistry

Volumn 55, Issue 4, 2012, Pages 1698-1705

  Bryan, Marian C ^a   Whittington, Douglas A ^a   Doherty, Elizabeth M ^a   Falsey, James R ^a   Cheng, Alan C ^a   Emkey, Renee ^a   Brake, Rachael L ^a   Lewis, Richard T ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(S) 1 (2 (3,4,5 TRIMETHOXYPHENYLAMINO)PYRIMIDIN 4 YL)PIPERIDINE 3 CARBOXYLIC ACID; (S) 1 (2 CHLOROPYRIMIDIN 4 YL)N (4 METHYLBENZYL)PIPERIDINE 3 CARBOXAMIDE; (S) ETHYL 1 (2 (3,4,5 TRIMETHOXYPHENYLAMINO)PYRIMIDIN 4 YL)PIPERIDINE 3 CARBOXYLATE; (S) ETHYL 1 (2 CHLOROPYRIMIDIN 4 YL)PIPERIDINE 3 CARBOXYLATE; (S) METHYL 3 ((1 (2 (3,4,5 TRIMETHOXY PHENYLAMINO)PYRIMIDIN 4 YL)PIPERIDINE 3 CARBOXAMIDO)METHYL)BENZOATE; (S) N (3 (4 MORPHOLINYL)BENZYL) 1 (2 ((3,4,5 TRIMETHOXYPHENYL)AMINO) 4 PYRIMIDINYL) 3 PIPERIDINECARBOXAMIDE; (S) N (3 BIPHENYLYLMETHYL) 1 (2 ((3,4,5 TRIMETHOXYPHENYL)AMINO) 4 PYRIMIDINYL) 3 PIPERIDINECARBOXAMIDE; (S) N (4 METHYLBENZYL) 1 (2 ((3,4,5 TRIMETHOXYPHENYL)AMINO) 4 PYRIMIDINYL) 3 PIPERIDINECARBOXAMIDE; (S) TERT BUTYL 3 (4 METHYLBENZYLCARBAMOYL)PIPERIDINE 1 CARBOXYLATE; AMIDE; ANAPLASTIC LYMPHOMA KINASE; PIPERIDINE CARBOXAMIDE DERIVATIVE; PIPERIDINE DERIVATIVE; PROTEIN KINASE INHIBITOR; SOMATOMEDIN C; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; STRUCTURE ACTIVITY RELATION; X RAY;

AMIDES; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; FLUORESCENCE RESONANCE ENERGY TRANSFER; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PIPERIDINES; PROTEIN CONFORMATION; PYRIMIDINES; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, IGF TYPE 1; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84857400756     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201565s     Document Type: Article

References (20)

1. Palmer, R. H.; Vernersson, E.; Grabbe, C.; Hallberg, B. Anaplastic lymphoma kinase: signalling in development and disease Biochem. J. 2009, 420, 345-361
2. Chiarle, R.; Voena, C.; Ambrogio, C.; Piva, R.; Inghirami, G. The anaplastic lymphoma kinase in the pathogenesis of cancer Nature Rev. Cancer 2008, 8, 11-23
3. Mastini, C; Martinengo, C.; Inghirami, G.; Chiarle, R. Anaplastic lymphoma kinase: an oncogene for tumor vaccination Int. J. Mol. Med. 2009, 87, 669-677
4. Lin, E.; Li, L; Guan, Y.; Soriano, R.; Rivers, C. S.; Mohan, S.; Pandita, A.; Tang, J.; Modrusan, Z. Exon Array Profiling Detects EML4-ALK Fusion in Breast, Colorectal, and Non-Small Cell Lung Cancers Mol. Cancer Res. 2009, 7, 1466-1476
5. Mossé, Y. P.; Laudenslager, M.; Longo, L.; Cole, K. A.; Wood, A.; Attiyeh, E. F.; Laquaglia, M. J.; Sennett, R.; Lynch, J. E.; Perri, P.; Laureys, G.; Speleman, F.; Kim, C.; Hou, C.; Hakonarson, H.; Torkamani, A.; Schork, N. J.; Brodeur, G. M.; Tonini, G. P.; Rappaport, E.; Devoto, M.; Maris, J. M. Identification of ALK as a major familial neuroblastoma predisposition gene Nature 2008, 455, 930-936
6. George, R. E.; Sanda, T.; Hanna, M.; Frohling, S.; Luther, W., II; Zhang, J.; Ahn, Y.; Zhou, W.; London, W. B.; McGrady, P.; Xue, L.; Zozulya, S.; Gregor, V. E.; Webb, T. R.; Gray, N. S.; Gilliland, D. G.; Diller, L.; Greulich, H.; Morris, S. W.; Meyerson, M.; Look, A. T. Activating mutations in ALK provide a therapeutic target in neuroblastoma Nature 2008, 455, 975-978
7. Pulford, K.; Lamant, L.; Espinos, E.; Jiang, Q.; Xue, L.; Turturro, F.; Delsol, G.; Morris, S. The emerging normal and disease-related roles of anaplastic lymphoma kinase Cell. Mol. Life Sci. 2004, 61, 2939-2953 (Pubitemid 40104592)
8. Dirks, W. G.; Fahnrich, S.; Lis, Y.; Becker, E.; MacLeod, R. A. F.; Drexler, H. G. Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines Int. J. Cancer 2002, 100, 49-56 (Pubitemid 34602064)
9. Webb, T. R.; Slavish, J.; George, R. E.; Look, A. T.; Xue, L.; Jiang, Q.; Cui, X.; Rentrop, W. B.; Morris, S. W. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy Expert Rev. Anticancer Ther. 2009, 9, 331-356
10. Kwak, E. L.; Bang, Y-J; Camidge, D. R.; Shaw, A. T.; Solomon, B.; Maki, R. G.; Ou, S-H I; Dezube, B. J.; Jänne, P. A.; Costa, D. B.; Varella-Garcia, M.; Kim, W-H; Lynch, T. J.; Fidias, P.; Stubbs, H.; Engelman, J. A.; Sequist, L. V.; Tan, W.; Gandhi, L.; Mino-Kenudson, M.; Wei, G. C.; Shreeve, S. M.; Ratain, M. J.; Settleman, J.; Christensen, J. G.; Haber, D. A.; Wilner, K.; Salgia, R.; Shapiro, G. I.; Clark, J. W.; Iafrate, A. J. Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer N. Engl. J. Med. 2010, 363, 1693-1703
11. Drew, A. E.; Al-Assaad, A. S.; Yu, V.; Andrews, P.; Merkel, P.; Szilvassy, S. J.; Emkey, R.; Lewis, R. T.; Brake, R. L. Comparison of two cell-based phosphoprotein assays to support screening and development of an ALK inhibitor J. Biomol. Screening 2011, 16 (2) 164-173
12. Iwahara, T.; Fujimoto, J.; Wen, D.; Cupples, R.; Bucay, N.; Arakawa, T.; Mori, S.; Ratzkin, B.; Yamamoto, T. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system Oncogene 1997, 14, 439-339
13. Ullrich, A.; Gray, A.; Tam, A. W.; Yang-Feng, T.; Tsubokawa, M.; Colluns, C.; Henzel, W.; Le Bon, T.; Kathuria, S.; Chen, E.; Jacobs, S.; Francke, U.; Ramachandran, J.; Fujita-Yamaguchi, Y. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity EMBO J. 1986, 5, 2503-2512
14. Gunby, R. H.; Ahmed, S.; Sottocornola, R.; Gasser, M.; Redaelli, S.; Mologni, L.; Tartari, C. J.; Belloni, V.; Gambacorti-Passerini, C.; Scapozza, L. Structural Insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling J. Med. Chem. 2006, 49, 5759-5768 (Pubitemid 44423712)
15. Hendrickson, A. W.; Haluska, P. Resistance pathways relevant to insulin-like growth factor-1 receptor-targeted therapy Curr. Opin. Invest. Drugs 2009, 10, 1032-1040
16. Zuccotto, F.; Ardini, E.; Casale, E.; Angiolini, M. Through the "Gatekeeper Door": Exploiting the Active Kinase Conformation J. Med. Chem. 2010, 53, 2681-2694
17. Lee, C. C.; Jia, Y.; Li, N.; Sun, X.; Ng, K.; Ambing, E.; Gao, M.-Y.; Hua, S.; Chen, C.; Kim, S.; Michellys, P.-Y.; Lesley, S. A.; Harris, J. L.; Spraggon, G. Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain Biochem. J. 2010, 430, 425-437
18. Velaparthia, U.; Wittman, M.; Liu, P.; Stoffan, K.; Zimmermann, K.; Sang, X.; Carboni, J.; Li, A.; Attar, R.; Gottardis, M.; Greer, A.; Chang, C. Y.; Jacobsen, B. L.; Sack, J. S.; Sun, Y.; Langley, D. R.; Balasubramanian, B.; Vyas, D. Discovery and initial SAR of 3-(1 H -benzo[ d ]imidazol-2-yl)pyridin- 2(1 H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R) Bioorg. Med. Chem. Lett. 2007, 17, 2317-2321 (Pubitemid 46484302)
19. Thomas, S.; Notari, S.; Semin, D.; Cheetham, J.; Woo, G.; Bence, J.; Schulz, C.; Provchy, J. Streamlined Approach to the Crude Compound Purification to Assay Process J. Liq. Chromatogr. Related Technol. 2006, 29, 701-717 (Pubitemid 43323289)
20. For more information, see KINOMEscan, a division of DiscoveRx, 11180 Roselle Street, San Diego, California 92121, United States; http://kinomescan. com/ (accessed Feb 7, 2012).