Synthesis and Src kinase inhibitory activity of 2-phenyl- and 2-thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles

Journal of Medicinal Chemistry

Volumn 48, Issue 11, 2005, Pages 3891-3902

  Boschelli, Diane H ^a   Wu, Biqi ^a   Sosa, Ana Carolina Barrios ^a,b   Durutlic, Haris ^a   Chen, Joan J ^a   Wang, Yan ^a   Golas, Jennifer M ^a   Lucas, Judy ^a   Boschelli, Frank ^a  

^a WYETH RESEARCH   (United States)

^b Roche Carolina   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYL 7 PHENYLAMINOTHIENO[3,2 B]PYRIDINE 6 CARBONITRILE; 2 THIENYL 7 PHENYLAMINOTHIENO[3,2 B]PYRIDINE 6 CARBONITRILE; BOSUTINIB; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; PYRIDINE DERIVATIVE; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; DRUG ACTIVITY; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; ISOMER; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CELL LINE; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; FIBROBLASTS; HUMANS; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); MICE; MICE, NUDE; NITRILES; PROTO-ONCOGENE PROTEINS C-ABL; PYRIDINES; RATS; SRC-FAMILY KINASES; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES; TRANSFECTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 20144361879     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050175p     Document Type: Article

References (36)

1. Boggon, T. J.; Eck, M. J. Structure and regulation of Src family kinases. Oncogene 2004, 23, 7918-7927.
2. Parsons, S. J.; Parsons, J. T. Src family kinases, key regulators of signal transduction. Oncogene 2004, 23, 7906-7909.
3. Irby, R. B.; Yeatman, T. J. Role of Src expression and activation in human cancer. Oncogene 2000, 19, 5636-5642.
4. Frame, M. C. Src in cancer: Deregulation and consequences for cell behavior. Biochim. Biophys. Acta 2002, 1602, 114-130.
5. Susva, M.; Missbach, M.; Green, J. Src inhibitors: Drugs for the treatment of osteoporosis, cancer or both? Trends Pharmacol. Sci. 2000, 21, 489-495.
6. Paul, R.; Zhang, Z. G.; Eliceiri, B. P.; Jiang, Q.; Boccia, A. D.; Zhang, R. L.; Chopp, M.; Cheresh, D. A. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat. Med. 2001, 7, 222-227.
7. Talamonti, M. S.; Roh, M. S.; Curley, S. A.; Gallick, G. E. Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer. J. Clin. Invest. 1993, 91, 53-60.
8. Ito, H.; Gardner-Thorpe, J.; Zinner, M. J.; Ashley, S. W.; Whang, E. E. Inhibition of tyrosine kinase Src suppresses pancreatic cancer invasiveness. Surgery 2003, 134, 221-226.
9. Wiener, J. R.; Windham, T. C.; Estrella, V. C.; Parikh, N. U.; Thall, P. F.; Deavers, M. T.; Bast, R. C.; Mills, G. B.; Gallick, G. E. Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers. Gynecol. Oncol. 2003, 88, 73-79.
10. Myoui, A.; Nishimura, R.; Williams, P. J.; Hiraga, T.; Tamura, D.; Michigami, T.; Mundy, G. R.; Yoneda, T. C-Src tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res. 2003, 63, 5028-5033.
11. Matsumoto, T.; Jiang, J.; Kiguchi, K.; Ruffino, L.; Carbajal, S.; Beltran, L.; Bol, D. K.; Rosenberg, M. P.; DiGiovanni, J. Targeted expression of c-Src in epidermal basal cells leads to enhanced skin tumor promotion, malignant progression, and metastasis. Cancer Res. 2003, 63, 4819-4828.
12. Boschelli, D. H. 4-Anilino-3-quinolinecarbonitriles: An emerging class of kinase inhibitors. Curr. Top. Med. Chem. 2002, 2, 1051-1063.
13. Boschelli, D. H. 4-Anilino-3-quinolinecarbonitriles: An emerging class of kinase inhibitors-An update. Med. Chem. Rev.-Online 2004, 1, 457-463.
14. Boschelli, D. H.; Ye, F.; Wang, Y. D.; Dutia, M.; Johnson, S. L.; Wu, B.; Miller, K.; Powell, D. W.; Yaczko, D.; Young, M.; Tischler, M.; Arndt, K.; Discafani, C.; Etienne, C.; Gibbons, J.; Grod, J.; Lucas, J.; Weber, J. M.; Boschelli, F. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J. Med. Chem. 2001, 44, 3965-3977.
15. Golas, J. M.; Arndt, K.; Etienne, C.; Lucas, J.; Nardin, D.; Gibbons, J.; Frost, P.; Ye, F.; Boschelli, D. H.; Boschelli, F. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 2003, 63, 375-381.
16. Boschelli, D. H.; Wu, B.; Barrios Sosa, A. C.; Durutlic, H.; Ye, F.; Raifeld, Y.; Golas, J. M.; Boschelli, F. Identification of 7-phenylaminothieno- [3,2-b]pyridine-6-carbonitriles as a new class of Src kinase inhibitors. J. Med. Chem. 2004, 47, 6666-6668.
17. Brown, S. D.; Armstrong, R. W. Parallel synthesis of Tamoxifen and derivatives on solid support via resin capture. J. Org. Chem. 1997, 62, 7076-7077.
18. Boschelli, D. H.; Wang, D. Y.; Ye, F.; Yamashita, A.; Zhang, N.; Powell, D.; Weber, J.; Boschelli, F. Inhibition of Src kinase activity by 4-anilino-7-thienyl-3-quinolinecarbonitriles. Bioorg. Med. Chem. Lett. 2002, 12, 2011-2014.
19. Boschelli, D. H.; Wang, Y. D.; Johnson, S.; Wu, B.; Ye, F.; Barrios Sosa, A. C.; Golas, J. M.; Boschelli, F. 7-Alkoxy-4-phenylamino-3- quinolinecarbonitriles as dual inhibitors of Src and Abl kinases. J. Med. Chem. 2004, 47, 1599-1601.
20. Boschelli, D. H.; Wang, Y. D.; Ye, F.; Wu, B.; Zhang, N.; Dutia, M.; Powell, D. W.; Wissner, A.; Arndt, K.; Weber, J. M.; Boschelli, F. Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3- qumolinecarbonitriles. J. Med. Chem. 2001, 44, 822-833.
21. Zhang, N.; Wu, B.; Powell, D.; Wissner, A.; Floyd, M. B.; Kovacs, E. D.; Toral-Barza, L.; Kohler, C. Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors. Bioorg. Med. Chem. Lett. 2000, 10, 2825-2828.
22. Berger, D.; Dutia, M.; Powell, D.; Wissner, A.; DeMorin, F.; Raifeld, Y.; Weber, J.; Boschelli, F. Substituted 4-anilino-7- phenyl-3- qumolinecarbonitriles as Src kinase inhibitors. Bioorg. Med. Chem. Lett. 2002, 12, 2989-2992.
23. Warmuth, M.; Damoiseaux, R.; Liu, Y.; Fabbro, D.; Gray, N. Src family kinases: Potential targets for the treatment of human cancer and leukemia. Curr. Pharm. Des. 2003, 9, 2043-2059.
24. Boschelli, D. H. Dual inhibitors of Src and Abl tyrosine kinases. Drug Des. Rev.-Online 2004, 1, 203-214.
25. Deininger, M. W. N.; Druker, B. J. SRCircumventing imatinib resistance. Cancer Cell 2004, 6, 108-110.
26. Sawyers, C. L. Resistance to imatinib: More and more mutations. Blood 2003, 102, 4-5.
27. La Rosee, P.; Corbin, A. S.; Stoffregen, E. P.; Deininger, M. W.; Druker, B. J. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to Imatinib mesylate (Gleevec, STI571). Cancer Res. 2002, 62, 7149-7153.
28. Huron, D. R.; Gorre, M. E.; Kraker, A. J.; Sawyers, C. L.; Rosen, N.; Moasser, M. M. A novel pyridopyrimidine inhibitor of Abl kinase is a picomolar inhibitor of Bcr-Abl-driven K562 cells and is effective against STI571-resistant Bcr-Abl mutants. Clin. Cancer Res. 2003, 9, 1267-1273.
29. von Bubnoff, N.; Veach, D. R.; Miller, W. T.; Li, W.; Saenger, J.; Peschel, C.; Bornmann, W. G.; Clarkson, B.; Duyster, J. Inhibition of wild-type and mutant Bcr-Abl by pyrido-pyrimidine-type small molecule kinase inhibitors. Cancer Res. 2003, 63, 6395-6404.
30. Tipping, A. J.; Baluch, S.; Barnes, D. J.; Veach, D. R.; Clarkson, B. M.; Bornmann, W. G.; Mahon, F. X.; Goldman, J. M.; Melo, J. V. Efficacy of dual-specific Bcr-Abl and Src-family kinase inhibitors in cells sensitive and resistant to imatinib mesylate. Leukemia 2004, 18, 1352-1356.
31. O'Hare, T.; Pollock, R.; Stoffregen, E. P.; Keats, J. A.; Abdullah, O. M.; Moseson, E. M.; Rivera, V. M.; Tang, H.; Metcalf, C. A., III.; Bohacek, R. S.; Wang, Y.; Sundaramoorthi, R.; Shakespeare, W. C.; Dalgarno, D.; Clackson, T.; Sawyer, T. K.; Deininger, M. W.; Druker, B. J. Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: Implications for CML. Blood 2004, 104, 2532-2539.
32. Roginskaya, V.; Zuo, S.; Caudell, E.; Nambudiri, G.; Kraker, A. J.; Corey, S. J. Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell crowth. Leukemia 1999, 13, 855-861.
33. Warmuth, M.; Bergmann, M.; Priess, A.; Hauslmann, K.; Emmerich, B.; Hallek, M. The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J. Biol. Chem. 1997, 272, 33260-33270.
34. Shah, N. P.; Tran, C.; Lee, F. Y.; Chen, P.; Norris, D.; Sawyers, C. L. Overriding Imatinib resistance with a novel ABL kinase inhibitor. Science 2004, 305, 399-402.
35. Lombardo, L. J.; Lee, F. Y.; Chen, P.; Norris, D.; Banish, J. C.; Behnia, K.; Castaneda, S.; Cornelius, L. A. M.; Das, J.; Doweyko, A. M.; Fairchild, C.; Hunt, J. T.; Inigo, I.; Johnston, K.; Kamath, A.; Kan, D.; Klei, H.; Marathe, P.; Pang, S.; Peterson, R.; Pitt, S.; Schieven, G. L.; Schmidt, R. J.; Tokarski, J.; Wen, M.-L.; Wityak, J.; Borzilleri, R. M. Discovery of N-(2-chloro-6- methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimi-din-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/ Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem. 2004, 47, 6658-6661.
36. Compounds were tested at least twice with the standard deviation reported within the brackets.