Discovery of small molecule c-Met inhibitors: Evolution and profiles of clinical candidates

Anti-Cancer Agents in Medicinal Chemistry

Volumn 10, Issue 1, 2010, Pages 7-27

  Underiner, Ted L ^a   Herbertz, Torsten ^a   Miknyoczki, Sheila J ^a  

^a CEPHALON INC   (United States)

Author keywords

C Met; Cancer; Kinase inhibitor; Ligand protein interactions; Oncogene; Small molecule crystal structure; Tyrosine kinase

Indexed keywords

3 [1 (2,6 DICHLORO 3 FLUOROPHENYL)ETHOXY] 5 [1 (4 PIPERIDINYL) 1H PYRAZOL 4 YL] 2 PYRIDINYLAMINE; AMG 102; AMG 458; ANTINEOPLASTIC AGENT; ARQ 197; AV 299; BENZYLTRIAZOLOTRIAZINE DERIVATIVE; BISINDOLOMALEIMIDE; BMS 777607; CYTOKINE RECEPTOR ANTAGONIST; E 7050; ERLOTINIB; FORETINIB; GEFITINIB; INCB 28060; JNJ 38877605; MGCD 265; MK 2461; N (3 CHLOROPHENYL) 3 [3,5 DIMETHYL 4 (4 METHYL 1 PIPERAZINYLCARBONYL) 1H PYRROL 2 YLMETHYLENE] 2,3 DIHYDRO N METHYL 2 OXO 1H INDOLE 5 SULFONAMIDE; OA5D5; PF 04217903; QUINOLINE DERIVATIVE; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SCH 900105; TANESPIMYCIN; TRIAZINE DERIVATIVE; TRIAZOLOTRIAZINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; XL 184; XL 880;

ADVANCED CANCER; AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ANGIOGENESIS; APOPTOSIS; AREA UNDER THE CURVE; BINDING SITE; CANCER CHEMOTHERAPY; CARCINOGENESIS; CARCINOGENICITY; CELL INVASION; CELL MOTILITY; CLINICAL TRIAL; CRYSTAL STRUCTURE; DIGESTIVE SYSTEM CANCER; DNA DAMAGE; DNA STRAND BREAKAGE; DOSE RESPONSE; DRUG BINDING; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG SELECTIVITY; DRUG TOLERABILITY; ENZYME ACTIVATION; FATIGUE; GASTROINTESTINAL SYMPTOM; GENE AMPLIFICATION; GEOMETRY; GLIOBLASTOMA; HEAD AND NECK CARCINOMA; HINGE REGION; HUMAN; HYDROGEN BOND; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; METASTASIS; MULTIPLE CYCLE TREATMENT; MUTAGENICITY; PATHOGENESIS; PROSTATE CANCER; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; STRUCTURE ACTIVITY RELATION; THYROID MEDULLARY CARCINOMA; X RAY CRYSTALLOGRAPHY;

EID: 77950797736     PISSN: 18715206     EISSN: None     Source Type: Journal    
DOI: 10.2174/1871520611009010007     Document Type: Review

References (92)

1. Jänne, P. A.; Gray, N.; Settleman, J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat. Rev. Drug Discov., 2009, 8 (9), 709-723.
2. Ma, W. W.; Adjei, A. A. Novel agents on the horizon for cancer therapy. CA Cancer J. Clin., 2009, 59(3), 111-137.
3. Zhang, J.; Yang, P. L.; Gray, N. S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer, 2009, 9(1), 28-39.
4. Christensen, J. G.; Burrows, J.; Salgia, R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett., 2005, 225(1), 1-26. (Pubitemid 40732764)
5. Comoglio, P. M.; Trusolino, L. Invasive growth: from development to metastasis. J. Clin. Invest., 2002, 109(7), 857-862. (Pubitemid 34275105)
6. Mazzone, M.; Comoglio, P. M. The Met pathway: master switch and drug target in cancer progression. FASEB J., 2006, 20, 1611-1621. (Pubitemid 44943798)
7. Sattler, M.; Salgia, R. c-Met as a therapeutic target. Update Cancer Ther., 2009, 3, 109-118.
8. Abounader, R.; Laterra, J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro-Oncology, 2005, 7(4), 436-451. (Pubitemid 41555616)
9. Jaing, W. G.; Martin, T. A.; Parr, C.; Davies, G.; Matsumoto, K.; Nakamura, T. Hepatocyte growth factor, its receptor and their potential value in cancer therapies. Crit. Rev. Oncol./Hematol., 2005, 53, 35-69. (Pubitemid 39656109)
10. Sattler, M.; Salgia, R. c-Met and hepatocyte growth factor: potential as novel targets in cancer therapy. Curr. Oncol. Rep., 2007, 9(2), 102-108. (Pubitemid 46332381)
11. Maulik, G.; Shrikhande, A.; Kijima, T.; Ma, P. C.; Morrison, P.T.; Salgia, R. Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev., 2002, 13(1), 41-59. (Pubitemid 34436961)
12. Cristiani, C.; Rusconi, L.; Perego, R.; Schiering, N.; Kalisz, H.M.; Knapp, S.; Isacchi, A. Regulation of the wild-type and Y1235Dmutant Met kinase activation. Biochemistry, 2005, 44(43), 14110-14119. (Pubitemid 41533036)
13. Bardelli, A.; Longati, P.; Williams, T.; Benvenuti, S.; Comoglio, P.M. A peptide representing the carboxyl-terminal tail of the Met receptor inhibits kinase activity and invasive growth. J. Biol. Chem., 1999, 274(41), 29274-29281. (Pubitemid 29477094)
14. Schmidt, L.; Junker, K.; Nakaigawa, N.; Kinjerski, T.; Weirich, G.; Miller, M.; Lubensky, I.; Neumann, H.; Brauch, H.; Decker, J.; Vocke, C.; Brown, J.A.; Jenkins, R.; Richard, S.; Bererheim, J.; Gerrard, B.; Dean, M.; Linehan, W.M.; Zbar, B. Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene, 1999, 18(14), 2343-2350. (Pubitemid 29192711)
15. Smolen, G. A.; Sordella, R.; Muir, B.; Mohapatra, G.; Barmettler, A.; Archibald, H.; Kim, W. J.; Okimoto, R. A.; Bell, D. W.; Sgori, D. C.; Christensen, J. G.; Settleman, J.; Haber, D. A. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl. Acad. Sci. USA, 2006, 103(7), 2316-2321. (Pubitemid 43271667)
16. Fan, S.; Ma, Y. X.; Gao, M.; Yuan, R. Q.; Meng, Q.; Goldberg, I. D.; Rosen, E. M. The mulitsubstrate adapter Gab1 regulated hepatocyte growth factor (scatter factor)-c-Met signaling for cell survival and DNA repair. Mol. Cell Biol., 2001, 21(15), 4968-4984. (Pubitemid 32656395)
17. Hiscox, S.; Jordan, N. J.; Harper, M.; McClelland, R.; Smith, C.; Nicholoson, R. I. Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast carcinoma cells: implications for tumour-stroma interactions. Endoc.-Relat. Cancer, 2004, 13(4), 1085-1099. (Pubitemid 46212564)
18. Engleman, J. A.; Zejnullahu, K.; Mitsudomi, T.; Song, Y.; Hyland, C.; Park, J. O.; Lindeman, N.; Gale, C.-M.; Zhao, X.; Christensen, J. G.; Kosaka, T.; Holmes, A. J.; Rogers, A. M.; Cappuzzo, F.; Mok, T.; Lee, C.; Johnson, B. E.; Cantley, L. C.; Jänne, P. A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science, 2007, 316(5827), 1039-1043. (Pubitemid 46799492)
19. Shattuck, D. L.; Miller, J. K.; Carraway K. L., III; Sweeney, C. Met receptor contributes to tratuzumab resistance of her2-overexpressin breast cancer cells. Cancer Res., 2008, 68(5), 1471-1477. (Pubitemid 351346855)
20. Agarwal, S.; Zerillo, C.; Kolmakova, J.; Christensen, J. G.; Harris, L.N; Rimm, D. L.; DiGiovanna, M. P.; Stern, D. F. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br. J. Cancer, 2009, 100(6), 941-949.
21. Kubo, T; Yamamoto, H. Y.; Lockwood, W. W.; Valencia, I.; Soh, J.; Peyton, M.; Jida, M.; Otani, H.; Fujii, T.; Ouchida, M.; Takigawa, N.; Kiura, K.; Shimizu, K.; Date, H.; Minna, J.D.; Varella- Garcia, M.; Lam, W.L.; Gazdar, A.F.; Toyooka, S. MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR kinase inhibitors. Int. J. Cancer, 2009, 124(8), 1778-1784.
22. Bachleitner-Hoffman, T.; Sun, M. Y.; Chen, C.-T.; Tang, L.; Song, L.; Zeng, Z.; Shah, M.; Christensen, J. G.; Rosen, N.; Solit, D. B.; Weiser, M R. HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells. Mol. Cancer Ther., 2008, 7(11), 3499-3508.
23. Tang, Z.; Du, R.; Jiang, S.; Wu., C; Barkauskas, D. S.; Richey, J.; Molter, J.; Lam, M.; Flask, C.; Gerson, S.; Dowlati, A.; Liu, L.; Lee, Z.; Halmos, B.; Wang, Y.; Kern, J. A.; Ma, P. C. Dual Met- EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib- resistant lung cancer. Br. J. Cancer, 2008, 99(6), 911-922.
24. Bean, J.; Brennan, C.; Shih, J. Y.; Riely, G.; Viale, A.; Wang, L.; Chitale, D.; Motoi, N.; Szoke, J.; Broderick, S.; Balak, M.; Chang, W. C.; Yu, C. J.; Gazdar, A.; Pass, H.; Rusch, V.; Gerald, W.; Huang, S. F.; Yang, P. C.; Miller, V.; Ladanyi, M.; Yang, C. H.; Pao, W. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl. Acad. Sci. USA, 2007, 104(52), 20932-20937.
25. Burgess, T.; Coxon, A.; Meyer, S.; Sun, J.; Rex, K.; Tsuruda, T.; Chen, Q.; Ho, S. Y.; Li, L.; Kaufman, S.; McDorman, K.; Cattley, R. C.; Sun, J.; Elliott, G.; Zhang, K.; Feng, X.; Jia, X. C.; Green, L.; Radinsky, R.; Kendall, K. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met dependent human tumors. Cancer Res., 2006, 66(3), 1721-1729. (Pubitemid 43259957)
26. Jin, H,; Yang, R.; Zheng, Z.; Romero, M.; Ross, J.; Bou-Resaln, H.; Carano, R. A. D.; Kasman, I.; Mai, E.; Young, J.; Zha, J.; Zhang, Z.; Ross, S.; Schwall, R.; Colbern, G.; Merchant, M. Met-Mab, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res., 2008, 68(11), 4360-4368.
27. Kakkar, T.; Ma, M.; Zhuang, Y.; Patton, A.; Hu, Z.; Mounho, B. Pharmacokinetics and safety of a fully human hepatocyte growth factor antibody, AMG 102, in cynomologus monkeys. Pharm. Res., 2007, 24(10), 1910-1918. (Pubitemid 47389247)
28. Ramanathan, R. K.; Egorin, M. J.; Eiseman, J. L.; Ramalingam, S.; Friedland, D.; Agarwala, S. S.; Ivy, S. P.; Potter, D. M.; Chatta, G.; Zuhowski, E. G.; Stoller, R. G.; Naret, C.; Guo, J.; Belani, C. P. Phase I and pharmacodynamic study of 17-(allylamino)-17- demethoxygeldanamycin in adult patients with refractory advanced cancers. Clin. Cancer Res., 2007, 13(6), 1769-1782. (Pubitemid 46952944)
29. Tam, E. M.; Runyon, S. T.; Santell, L.; Quan, C.; Yao, X.; Kirchofer, D.; Skelton, N. J.; Lazarus RA Noncompetitive inhibition of hepatocyte growth factor dependent Met signaling by a phage derived peptide. J. Mol. Biol., 2009, 385(1), 79-90.
30. Wang S; Pashtan I; Tsutsumi S; Xu W; Neckers L Cancer cells harboring MET gene amplification activate alternative signaling pathways to escape MET inhibition but remain sensitive to Hsp90 inhbitors. Cell Cycle, 2009, 8 (13), 2050-2056.
31. Abounader, R.; Raganathan, S.; Lal, B.; Fielding, K.; Book, A.; Dietz, H.; Burger, P.; Laterra, J. Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c-Met expression. J. Natl. Cancer Inst., 1999, 91(18), 1548-1556. (Pubitemid 29457959)
32. La Merie Business Intelligence. Competitior Analysis: c-Met/HGF Inhibitor Review. La Merie:Barcelona, October 2008.
33. Abidoye, O.; Murukurthy, N.; Salgia, R. Review of clinic trials: agents targeting c-Met. Rev. Recent Clin. Trials, 2007, 2 (2), 143-147. (Pubitemid 46773882)
34. Cui, J. Inhibitors targeting hepatocyte growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases. Expert Opin. Ther. Pat., 2006, 16, 713-718. (Pubitemid 43731158)
35. Dussault, I.; Bellon, S. From concept to reality: the long road to c- Met and RON receptor tyrosine kinase inhibitors for the treatment of cancer. Anti-Cancer Agents Med. Chem., 2009, 9(2), 221-229.
36. Eder, J. P.; Vande Woude, G. F.; George, F.; Boerner, S. A.; Lo- Russo, P. Novel therapeutic inhibitors of the c-Met signaling Pathway in cancer. Clin. Cancer Res., 2009, 15(7), 2207-2214.
37. Knudsen, B. S.; Vande Woude, G. F. Showering c-Met-dependent cancers with drugs. Curr. Opin. Genetic Dev., 2008, 18(1), 87-96.
38. Giubellino, A.; Linehan, W. M.; Bottaro, D. P. Targeting the Met signaling pathway in renal cancer. Expert Rev. Anticancer Ther., 2009, 9(6),785-793
39. Liu, X.; Yao, W.; Newton, R. C.; Scherle, P. A. Targeting the c- Met signaling pathway for cancer therapy. Expert Opin. Investig. Drugs, 2008, 17(7), 997-1011.
40. Comogilo, P. M.; Giordano, S.; Trusolino, L. Drug development of Met inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug Discov., 2008, 7, 504-516. (Pubitemid 351767118)
41. You, W.-K.; McDonald, D. M. The hepatocyte growth factor / c- Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep., 2008, 41(12), 833-839.
42. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T. The proten kinases complement of the human genome. Science, 2002, 298 (5600), 1912-1926. (Pubitemid 35425239)
43. Backes, A. C.; Felber, B. Z.; Klebl, B.; Muller, G. Small-molcule inhibitors binding to protein kinases. Part I: exceptions from the traditional pharmacophore approach of type I inhibition. Expert Opin. Drug Discov., 2008, 3(12), 1409-1425.
44. Backes, A. C.; Felber, B. Z.; Klebl, B.; Muller, G. Small-molcule inhibitors binding to protein kinases. Part II: the novel pharmacophore approach of type II and type III inhibition. Expert. Opin. Drug Discov., 2008, 3(12), 1427-1449.
45. Buijsman, R. In: Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective; Kubinyi and Müller, Eds.; Wiley-VCH Verlag GmbH, Weinheim, 2004; pp. 191-220.
46. Liao, J. J.-L. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J. Med. Chem., 2007, 50(3), 409-424.
47. Liu, Y.; Gray, N. S. Rational design of inhibitors that bind to inactive kinase conformations. Nat. Chem. Bio., 2006, 2(7), 358-364. (Pubitemid 43936934)
48. Schiering, N.; Knapp, S.; Marconi, M.; Flocco, M. M.; Cui, J.; Perego, R.; Rusconi, L.; Cristiani, C. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc. Natl. Acad. Sci. USA, 2003, 100(22), 12654-12659. (Pubitemid 37339954)
49. Noble, M. E. M.; Endicott, J. A.; Johnson, L. N. Protein kinase inhibitors: insights into drug design from structure. Science, 2004, 303(5665), 1800-1805. (Pubitemid 38374863)
50. Traxler, P.; Furet, P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol. Ther., 1999, 82(2-3), 196-206. (Pubitemid 29255915)
51. Ghose, A. K.; Herbertz, T.; Pippin, D. A.; Salvino, J. M.; Mallamo, J. P. Knowledge based prediction of ligand binding modes and rational inhibitor design for kinase drig discovery. J. Med. Chem., 2008, 51(17), 5149-5171.
52. Wang, W.; Marimuthu, A.; Tsai, J.; Kumar, A.; Krupka, H. I.; Zhang, C.; Powell, B.; Suzuki, Y.; Nguyen, H.; Tabrizizad, M.; Luu, C.; West, B. L. Structural characterization of autoinhibited c- Met kinase produced by coexpression in bacteria with phosphatase. Proc. Natl. Acad. Sci. USA, 2006, 103(11), 3563-3568. (Pubitemid 43376595)
53. Bellon, S. F.; Kaplan-Lefko, P.; Yang, Y.; Zhang, Y.; Moriguchi, J.; Rex, K.; Johnson, C. W.; Rose, P.E.; Long, A.M.; O'Connor, A. B.; Gu, Y.; Coxon, A.; Kim, T.-S.; Tasker, A.; Burgess, T. L.; Dussault, I. c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations. J. Biol. Chem., 2008, 283(5), 2675-2683.
54. Gajiwala, K. S.; Wu, J. C.; Christensen, J.; Deshmukh, G. D.; Diehl, W.; DiNitto, J. P.; English, J. M.; Greig, M. J.; He, Y.-A.; Jacques, S. L.; Lunney, E. A.; McTigue, M.; Molina, D.; Quenzer, T.; Wells, P. A.; Yu, X.; Zhang, Y.; Zou, A.; Emmett, M. R.; Marshall, A. G.; Zhang, H.-W.; Demetri, G. D. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc. Natl. Acad. Sci. USA, 2009, 106(5), 1542-1547.
55. D'Angelo, N. D.; Bellon, S. F.; Booker, S. K.; Cheng, Y.; Coxon, A.; Dominguez, C.; Fellows, I.; Hoffman, D.; Hungate, R.; Kaplan- Lefko, P.; Lee, M. R.; Li, C.; Liu, L.; Rainbeau, E.; Reider, P. J.; Rex, K.; Siegmund, A.; Sun, Y.; Tasker, A. S.; Xi, N.; Xu, S.; Yang, Y.; Zhang, Y.; Burgess, T. L.; Dussault, I.; Kim, T. S. Design, synthesis, and biological evaluation of potent c-Met inhibitors. J. Med. Chem., 2008, 51(18), 5766-5779.
56. Levinson, N. M.; Kuchment, O.; Shen, K.; Young, M. A.; Koldobskiy, M.; Karplus, M.; Cole, P. A.; Kuriyan, J. A Src-like inactive confirmation in the Abl tyrosine kinase domain. PLoS Biol., 2006, 4(5), e144. (Pubitemid 43748222)
57. Cai, Z.-W.; Wei, D.; Schroeder, G. M.; Cornelius, L. A.; Kim, K.; Chen, X.-T.; Schmidt, R. J.; Williams, D. K.; Tokarski, J. S.; An, Y.; Sack, J. S.; Manne, V.; Kamath, A.; Zhang, Y.; Marathe, P.; Hunt, J. T.; Lombardo, L. J.; Fargnoli, J.; Borzilleri, R. M. Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors. Biorg. Med. Chem. Lett., 2008, 18(11), 3224-3229.
58. Kim, K. S.; Zhang, L.; Schmidt, R.; Cai, Z. W.; Wei, D.; Williams, D. K.; Lombardo, L. J.; Trainor, G. L.; Xie, D.; Zhang, Y.; An, Y.; Sack, J. S.; Tokarski, J. S.; Darienzo, C.; Kamath, A.; Marathe, P.; Zhang, Y.; Lippy, J.; Jeyaseelan, R.; Wautlet, B.; Henley, B.; Gullo-Brown, J.; Manne, V.; Hunt, J. T.; Fargnoli, J.; Borzilleri, R. M. Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. J. Med. Chem., 2008, 51(17), 5330-5341.
59. Schroeder, G. M.; Chen, X.-T.; Williams, D. K.; Nirschl, D. S.; Cai, Z.-H.; Wei, D.; Tokarski, J. S.; An, Y.; Sack, J.; Chen, Z.; Huynh, T.; Vaccaro, W.; Poss, M.; Wautlet, B.; Gullo-Brown, J.; Kellar, K.; Manne, V.; Hunt, J. T.; Wong, T. W.; Lombardo, L. J.; Fargnoli, J.; Borzilleri, R. M. Identification of pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of Met kinase. Biorg. Med. Chem. Lett., 2008, 18(6), 1945-1951. (Pubitemid 351380893)
60. Schroeder, G. M.; An, Y.; Cai, Z.-H.; Chen, X.-T.; Clark, C.; Cornelius, L. A. M.; Dai, J.; Gullo-Brown, J.; Gupta, A.; Henley, B.; Hunt, J. T.; Jeyaseelan, R.; Kamath, A.; Kim, K.; Lippy, J.; Lombardo, L. J.; Manne, V.; Oppenheimer, S.; Sack, J. S.; Schmidt, R. J.; Shen, G.; Stefanski, K.; Tokarski, J. S.; Trainor, G. L.; Wautlet, B. S.; Wei, D.; Williams, D. K.; Zhang, Y.; Zhang, Y.; Fargnoli, J.; Borzilleri, R. M. Discovery of N-(4-(2-amino-3- chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4- fluorophenyl)-2-oco-1,2- dihydropyridine-3-carboxamide (BMS- 777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J. Med. Chem., 2009, 52(5), 1251-1254.
61. Albrecht, B. K.; Harmange, J.-C.; Bauer, D.; Berry, L.; Bode, C.; Boezio, A. A.; Chen, A.; Choquette, D.; Dussault, I.; Fridrich, C.; Hirai, S.; Hoffman, D.; Larrow, J. F.; Kaplan-Lefko, P.; Lin, J.; Lohman, J.; Long, AM.; Moriguchi, J.; O'Connor, A.; Potashman, M. H.; Reese, M.; Rex, K.; Siegmund, A.; Shah, K.; Shimanovich, R.; Springer, S. K.; Teffera, Y.; Yang, Y.; Zhang, Y.; Bellon, S. F. Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase. J. Med. Chem., 2008, 51(10), 2879-2882.
62. Porter, J.; Lumb, S.; Franklin, R. J.; Gascon-Simorte, J. M.; Calmiano, M.; Le Rich, K.; Lallemand, B.; Keyaerts, J.; Edwards, J.; Maloney, A.; Delgado, J.; King, L.; Foley, A.; Lecomte, F.; Reuberson, J.; Meier, C.; Batchelor, M. Discovery of 4-azaindoles as novel inhbitors of c-Met kinase. Biorg. Med. Chem. Lett., 2009, 19, 2780-2784.
63. Porter, J.; Lumb, S.; Lecomte, F.; Reuberson, J.; Foley, A.; Calmiano, M.; Le Rich, K.; Edwards, H.; Delgado, J.; Franklin, R. J.; Gascon-Simorte, JM.; Maloney, A.; Meier, C.; Batchelor, M. Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase. Biorg. Med. Chem. Lett., 2009, 19, 397-400.
64. Jie-F; Vojkovsky, T.; Huang, P.; Liang, C.; Do, S.; Huy, S.; Koenig, M.; Cui, J. Preparation of triazolotriazines as c-Met modulators for treating cancer. PCT Int. Appl., WO2005010005, February 03, 2005.
65. Lauffer, D.; Aronov, A.; Li, P.; Deininger, D.; Mcginty, K.; Stamos, D.; Come, J.; Stewart, M. Preparation of fused triazoles as inhibitors of c-Met tyrosine kinase. PCT Int. Appl., WO2007064797, June 07, 2007.
66. Lu, T.; Alexander, R.; Connors, R. W.; Cummings, M. D.; Galemmo, R. A.; Hufnagel, H. R.; Johnson, D. L.; Khalil, E.; Leonard, K. A.; Markotan, T. P.; Maroney, A. C.; Sechler, J. L.; Travins, J. M.; Tuman, R. W. Preparation of triazolopyridazines as tyrosine kinase modulators. PCT Int. Appl., WO200707075567, July 07, 2007.
67. Prous Science Integrity, JNJ-38877605. Drug Data Rep., 2008, 30(4), 362.
68. Cheng, H.; Cui, J.; Jingrong, J.; Hoffman, J.; Jia, L.; Kania, R. S.; Le, P. T. Q.; Nambu, M. D.; Pairish, M. A.; Shen, H.; Tran-Dube, M. B. Preparation of triazolopyridazines as c-Met kinase inhibitor. PCT Int. Appl., WO2007138472, December 06, 2007.
69. Cheng, H.; Cui, J.; Hoffman, J.; Jia, L.; Johnson, M. C.; Kania, R. S.; Le, P. T. Q.; Nambu, M. D.; Pairish, M. A.; Shen, H.; Tran- Dube, M. B. Preparation of triazolopyrazine derivatives for treating hyperproliferative disorders. U. S. Pat. Appl. Publ., US2007 7265272, November 15, 2007.
70. Timofeevski, S. L.; McTigue, M. A.; Ryan, K. R.; Cui, J.; Zou, H. Y.; Zhu, J. X.; Chau, F.; Alton, G.; Karlicek, S.; Christensen, J. G.; Murray, B. W. Enzymatic characterization of c-Met receptor tyrosine kinase oncogenic mutants and kinetic studies with aminopyridine and triazolopyrazine inhibitors. Biochemistry, 2009, 48(23), 5339-5349.
71. Zhuo, J.; Zhang, C.; Xu, M.; Qian, D.-Q.; Yao, W.; Jalluri, R. K. Preparation of triazolotriazine derivatives as kinase inhibitors. U.S. Pat. Appl. Publ., US2008039457, February 14, 2008.
72. Smith, C. R.; Bounaud, P.-Y.; Jefferson, E. A.; Lee, P. S.; Torres, E. Preparation of triazolopyridazine protein kinase modulators. PCT Int, Appl., WO 2008051805, May 02, 2008.
73. Bounaud, P.-Y.; Smith, C.; Jefferson, E. A. Preparation of bicyclic triazoles as protein kinase modulators. PCT Int. Appl., WO2008051805, May 02, 2008.
74. Albrecht, B.; Bauer, D.; Bellon, S.; Bode, C.; Booker, S.; Boezio, A.; Choquette, D.; D'Amico, D.; Harmange, J.-C.; Hirai, S.; Hungate, R. W.; Kim, T.-S.; Lewis, R.; Liu, L.; Lohman, J.; Norman, M.; Potashman, M.; Siegmund, A.; Springer, S.; Stec, M.; Xi, N.; Yang, K. Preparation of fused heterocyclic derivatives for treating HGF mediated diseases. PCT Int. Appl., WO2008008539, January 17, 2008.
75. Teffera, Y.; Colletti, A. E.; Harmange, J.-C.; Hollis, L. S.; Albrecht, B. K.; Boezio, A.; Alessandro, A.; Liu, J.; Zhao, Z. Chemical reactivity of methoxy 4-O-aryl quinolines: identification of glutathione displacement products in vitro and in vivo. Chem. Res. Toxicol., 2008, 21(11), 2216-2222.
76. Cui, J. Preparation of aminoheteroaryl compounds as protein kinase inhibitors. PCT Int. Appl., WO2004076412, September 10, 2004.
77. Cui, J.; Funk, L. A.; Jia, L.; Kung, P.-P.; Meng, J. J.; Nambu, M. D.; Pairish, M. A.; Shen, H.; Tran-Dube, M. B. Preparation of pyrazole-substituted aminoheteroaryl compounds as c-Met inhibtors for use against cancer and other abnormal cell growth disorders. PCT Int. Appl., WO2006021881, March 02, 2006.
78. Zou, H. Y.; Qiuhua, L.; Lee, J. H.; Arango, M. E.; McDonnell, S. R.; Yamazaki, S.; Koudriakova, T. B.; Alton, G.; Cui, J.; Kung, P.- P.; Nambu, M. D.; Los, G.; Bender, S.; Mroczkowski, B.; Christensen, J. G. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res., 2007, 67(9), 4408-4417.
79. Christensen, J. G.; Zou, H.; Arango, M.; Li, Q.; Lee, J. H.; McDonnell, S. R.; Yamazaki, S.; Alton, G.; Mroczkowski, B.; Los, G. Cytoreductive antitumor activity of PF-2341066, a novel inhbitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol. Cancer Ther., 2007, 6(12 (Pt 1)), 3389-3395.
80. McDermott, U.; Lafrate, A. J.; Gray, N. S.; Shioda, T.; Classon, M.; Maheswaran, S.; Zhou, W.; Choi, H. G.; Smith, S. L.; Dowell, L.; Ulkus, L. E.; Kuhlmann, G.; Greninger, P.; Christensen, J. G.; Haber, D. A.; Settleman, J. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res., 2008, 68(9), 3389-3395.
81. Yamazaki, S.; Skaptason, J.; Romero, D.; Lee, J. H.; Zou, H. Y.; Christensen, J. G.; Koup, J. R.; Smith, B. J.; Koudriakova, T. Pharmacokinetic-pharmacodynamic modeling of biomarkers response and tumor growth inhibition to an orally available c-Met kinase inhibitor in human tumor xenografts. Drug Metab. Dispos., 2008, 36(7), 1268-1274.
82. Fujiwara, Y.; Senga, T.; Nishitoba, T.; Osawa, T.; Miwa, A.; Nakamura, K. Preparation of quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of hepatocyte growth factor receptor as antitumor agents. PCT Int. Appl., WO2003000660, January 03, 2003.
83. Kubo, K.; Furuta, T.; Osawa, T.; Miwa, A. Preparation of thienopyridine and quinoline derivatives as inhibitors of c-Met autophosphorylation for the treatment of cancer. PCT Int. Appl., WO2006104161, October 05, 2006.
84. Claridge, S.; Raeppel, F.; Granger, M.-C.; Berstein, N.; Saavedra, O.; Zhan, L.; Llewellyn, D.; Wahhab, A.; Deziel, R.; Rahil, D.; Beaulieu, N.; Nguyen, H.; Dupont, I.; Barsalou, A.; Beaulieu, C.; Chute, I.; Gravel, S.; Robert, M.-F.; Lefebvre, S.; Dubay, M.; Pascal, R.; Gillespie, J.; Jin, Z.; Wang, J.; Besterman, J. M.; Macleod, A. R.; Vaisburg, A. Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases. Biorg. Med. Chem. Lett., 2008, 18(9), 2793-2798.
85. Raeppel, S.; Claridge, S.; Saavedra, O.; Gaudette, F.; Zhan, L.; Mannion, M.; Zhou, N.; Raeppel, F.; Granger, M.-C.; Isakovic, L.; Deziel, R.; Nguyen, H.; Beaulieu, N.; Beaulieu, C.; Dupont, I.; Robert, M.-F.; Lefebvre, S.; Dubay, M.; Rahil, J.; Wang, J.; Ste- Croix, H.; McCleod, R.; Besterman, J. M.; Vaisburg, A. N-(3- fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3- phenylimidazolidine-1-carboxamides: a novel series of dual c- Met/VEGFR2 receptor tyrosine kinase inhibitors. Biorg. Med. Chem. Lett., 2009, 19(5), 1323-1328.
86. Bannen, L. C.; Chan, D. S.; Chen, J.; Dalrymple, L. E.; Forsyth, T. P.; Huynh, T. P.; Jammalamadaka, V.; Khoury, R. G.; Leahy, J. W.; Mac, M. B.; Mann, G.; Mann, L. W.; Nuss, J. M.; Parks, J. J.; Takeuchi, C. S.; Wang, Y.; Xu, W. Preparation of quinolines and quinazolines as inhibitors of c-Met and other tyrosine kinases and therapeutic uses against proliferative diseases. PCT Int. Appl., WO2005030140, April 07, 2005.
87. Liu, L.; Greger, J.; Shi, H.; Liu, Y.; Greshock, J.; Annan, R.; Halsey, W.; Sathe, G. M.; Martin, A.-M.; Gilmer, T. M. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res., 2009, 69(17), 6871-6878
88. Matsushima, T.; Takahashi, K.; Funasaka, S.; Obaishi, H.; Shirotori, S. Novel pyridine derivatives and pyrimidine derivatives as HGFR inhibitors and their preparation and use in the treatment of diseases. U. S. Pat. Appl. Publ., US2008319188, December 25, 2008.
89. A study of E7050 administered orally to patients with advanced solid tumors (NCT00921869). http://clinicaltrials.gov/ct2/show/NCT00869895 Clinical Trials Gov (accessed September 2009).
90. Liu, L.; Siegmund, A.; Xi, N.; Kaplan-Lefko, P.; Rex , K.; Chen, A.; Lin, J.; Moriguchi, J.; Berry, L.; Huang, L.; Teffera, Y.; Yang, Y.; Zhang, Y.; Bellon, S. F.; Lee, M.; Shimanovich, R.; Bak, A.; Dominguez, C.; Norman, M.; Harmange, J.-C.; Dussault, I.; Kim, T.-S. Discovery of a potent, selective, and orally bioavailable c- Met inhibitor:1-(2-Hydroxy-2-methylpropyl)-N-(5-(7- methoxyquinolin- 4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazole-4-carboxamide (AMG 458). J. Med. Chem., 2008, 51, 3688-3691.
91. Li, C. J.; Ashwell, M. A.; Hill, J.; Moussa, M. M.; Munshi, N. Preparation of malemide derivatives, pharmaceutical compositions and methods for treatment of cancer. PCT Int. Appl., WO2006086484, August 17, 2006.
92. Jemal, A.; Siegel, R.; Ward, E.; Hoa, Y.; Xu, J.; Thun, M. J. Cancer statistics 2009. CA Cancer J. Clin., 2009, 59(4), 225-249.