Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds

Journal of Medicinal Chemistry

Volumn 51, Issue 16, 2008, Pages 4948-4956

  Lawrence, Harshani R ^a   Pireddu, Roberta ^a   Chen, Liwei ^a   Luo, Yunting ^a   Sung, Shen Shu ^a   Szymanski, Ann Marie ^a   Yip, M L Richard ^a,d   Guida, Wayne C ^a,b,c   Sebti, Saïd M ^a,b   Wu, Jie ^a,b   Lawrence, Nicholas J ^a,b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

^c UNIVERSITY OF SOUTH FLORIDA   (United States)

^d CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [2 [5 [N [4 CHLORO 3 (TRIFLUOROMETHYL)BENZYL]SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [(2 NITROPHENYL)HYDRAZONO] 2 OXO 2,3 DIHYDRO 1H INDOLE 5 SULFONAMIDE; 3 [(2 NITROPHENYL)HYDRAZONO] 2 OXO 2,3 DIHYDRO 1H INDOLE 5 SULFONIC ACID 4 CHLOROBENZYLAMIDE; 3 [2 (2 CARBOXYPHENYL)HYDRAZONO] 2 OXOINDOLINE 5 CARBOXYLIC ACID; 3 [2 (2 NITROPHENYL)HYDRAZONO] 2 OXOINDOLINE 5 SULFONIC ACID; 3 [2 (3 CARBOXYPHENYL)HYDRAZONO] 2 OXOINDOLINE 5 CARBOXYLIC ACID; 3 [2 [5 (4 CHLOROBENZYLCARBAMOYL) 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (2 CHLOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (2,4 DICHLOROPHENETHYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (3 CHLORO 4 FLUOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (3 CHLOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (4 CHLOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (4 FLUOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N (4 METHYLBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [2 [5 [N [4 CHLORO 3 (TRIFLUOROMETHYL)BENZYL]SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 3 [N' (5 ISOPROPYLSULFAMOYL 2 OXO 1,2 DIHYDROINDOL 3 YLIDENE)HYDRAZINOL]BENZOIC ACID; 4 [2 [5 (N BENZYLSULFAMOY1) 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 4 [2 [5 [N (2 CHLOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 4 [2 [5 [N (4 CHLOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 4 [2 [5 [N (4 FLUOROBENZYL)SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 4 [2 [5 [N [4 CHLORO 3 (TRIFLUOROMETHYL)BENZYL]SULFAMOYL] 2 OXOINDOLIN 3 YLIDENE]HYDRAZINYL]BENZOIC ACID; 4 [N' (5 ISOPROPYLSULFAMOYL 2 OXO 1,2 DIHYDROINDOL 3 YLIDENE)HYDRAZINO]BENZOIC ACID; BENZOIC ACID DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; NSC 117199; OXINDOLE; PROTEIN TYROSINE PHOSPHATASE 1B; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PROTEIN TYROSINE PHOSPHATASE SHP 1; PROTEIN TYROSINE PHOSPHATASE SHP 2; SULFONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG DESIGN; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; MASS SPECTROMETRY; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

BINDING SITES; INDOLES; INHIBITORY CONCENTRATION 50; MODELS, MOLECULAR; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 11; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 6; SRC HOMOLOGY DOMAINS; SULFONIC ACIDS;

EID: 50249093762     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8002526     Document Type: Article

References (47)

1. Bridges, A. J. Chemical inhibitors of protein kinases. Chem. Rev. 2001, 101, 2541-2571.
2. (a) Bialy, L.; Waldmann, H. Inhibitors of protein tyrosine phosphatases: next-generation drugs. Angew. Chem. Int. Ed. 2005, 44, 3814-3839.
3. (b) Jiang, Z.-X.; Zhang, Z.-Y. Targeting PTPs with small molecule inhibitors in cancer treatment. Cancer Metastasis Rev. 2008, 27, 263-272.
4. (c) Tautz, L.; Pellecchia, M.; Mustelin, T. Targeting the PTPome in human disease. Expert Opin. Ther. Targets 2006, 10, 157-177.
5. (d) Dewang, P. M.; Hsu, N. M.; Peng, S. Z.; Li, W. R. Protein tyrosine phosphatases and their inhibitors. Curr. Med. Chem 2005, 12, 1-22.
6. (e) Tautz, L.; Mustelin, T. Strategies for developing protein tyrosine phosphatase inhibitors. Methods 2007, 42, 250-260.
7. Alonso, A.; Sasin, J.; Bottini, N.; Friedberg, I.; Friedberg, I.; Osterman, A.; Godzik, A.; Hunter, T.; Dixon, J.; Mustelin, T. Protein tyrosine phosphatases in the human genome. Cell 2004, 117, 699-711.
8. (a) Chan, G.; Kalaitzidis, D.; Neel, B. G. The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev. 2008, 27, 179-192.
9. (b) Mohi, M. G.; Neel, B. G. The role of Shp2 (PTPN11) in cancer. Curr. Opin. Genet. Dev. 2007, 17, 23-30.
10. (c) Mannell, H.; Kroetz, F. The role of SHP-2 in cell signaling and human disease. Curr. Enzyme Inhib. 2007, 3, 264-272.
11. (d) Neel, B. G.; Gu, H.; Pao, L. The "Shp"ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem. Sci. 2003, 28, 284-293.
12. (a) Dance, M.; Montagner, A.; Salles, J.-P.; Yart, A.; Raynal, P. The molecular functions of Shp2 in the Ras/mitogen-activated protein kinase (ERK 1/2) pathway. Cell. Signalling 2008, 20, 453-459.
13. (b) Chong, Z. Z.; Maiese, K. The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury. Histol. Histopathol. 2007, 22, 1251-1267.
14. (c) Xu, R. Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia. Cell Res. 2007, 17, 295-297.
15. (d) Feng, G. S. Shp-2 tyrosine phosphatase: signaling one cell or many. Exp. Cell Res. 1999, 253, 47-54.
16. Nishida, K.; Hirano, T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci. 2003, 94, 1029-1033.
17. Gu, H.; Neel, B. G. The "Gab" in signal transduction. Trends Cell Biol. 2003, 13, 122-30.
18. Deb, T. B.; Wong, L.; Salomon, D. S.; Zhou, G.; Dixon, J. E.; Gutkind, J. S.; Thompson, S. A.; Johnson, G. R. A common requirement for the catalytic activity and both SH2 domains of SHP-2 in mitogen-activated protein (MAP) kinase activation by the ErbB family of receptors. J. Biol. Chem. 1998, 273, 16643-16646.
19. Cunnick, J. M.; Dorsey, J. F.; Munoz-Antonia, T.; Mei, L.; Wu, J. Requirement of SHP2 binding to Grb2-associated binder-1 for mitogen-activated protein kinase activation in response to lysophosphatidic acid and epidermal growth factor. J. Biol. Chem. 2000, 275, 13842-13848.
20. Maroun, C. R.; Naujokas, M. A.; Holgado-Madruga, M.; Wong, A. J.; Park, M. The tyrosine phosphatase SHP-2 is required for sustained activation of extracellular signal-regulated kinase and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol. Cell. Biol. 2000, 20, 8513-8525.
21. Furge, K. A.; Zhang, Y. W.; Vande Woude, G. F. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 2000, 19, 5582-5589.
22. Bentires-Alj, M.; Kontaridis, M. I.; Neel, B. G. Stops along the RAS pathway in human genetic disease. Nat. Med. 2006, 12, 283-285.
23. Higashi, H.; Tsutsumi, R.; Muto, S.; Sugiyama, T.; Azuma, T.; Asaka, M.; Hatakeyama, M. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 2002, 295, 683-686.
24. Meyer-ter-Vehn, T.; Covacci, A.; Kist, M.; Pahl, H. L. Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun. J. Biol. Chem. 2000, 275, 16064-16072.
25. Hof, P.; Pluskey, S.; Dhe-Paganon, S.; Eck, M. J.; Shoelson, S. E. Crystal structure of the tyrosine phosphatase SHP-2. Cell 1998, 92, 441-450.
26. Shen, K.; Keng, Y. F.; Wu, L.; Guo, X. L.; Lawrence, D. S.; Zhang, Z. Y. Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial library and screening procedure. J. Biol. Chem. 2001, 276, 47311-47319.
27. Huang, P.; Ramphal, J.; Wei, J.; Liang, C.; Jallal, B.; McMahon, G.; Tang, C. Structure-based design and discovery of novel inhibitors of protein tyrosine phosphatases. Bioorg. Med. Chem. 2003, 11, 1835-1849.
28. Nören-Müller, A.; Reis-Corrêa, I.; Prinz, H.; Rosenbaum, C.; Saxena, K.; Schwalbe, H. J.; Vestweber, D.; Cagna, G.; Schunk, S.; Schwarz, O.; Schiewe, H.; Waldmann, H. Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis. Proc. Nat. Acad. Sci. U.S.A. 2006, 103, 10606-10611.
29. Chen, L.; Sung, S. S.; Yip, M. L. R.; Lawrence, H. R.; Ren, Y.; Guida, W. C.; Sebti, S. M.; Lawrence, N. J.; Wu, J. Discovery of a novel Shp2 protein tyrosine phosphatase inhibitor. Mol. Pharmacol. 2006, 70, 562-570.
30. Neel, B. G.; Tonks, N. K. Protein tyrosine phosphatases in signal transduction. Curr. Opin. Cell Biol. 1997, 9, 193-204.
31. Poole, A. W.; Jones, M. L. A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine phosphatases by the C-terminal tail. Cell. Signalling 2005, 17, 1323-1332.
32. Yang, J.; Liu, L.; He, D.; Song, X.; Liang, X.; Zhao, Z. J.; Zhou, G. W. Crystal structure of human protein-tyrosine phosphatase SHP-1. J. Biol. Chem. 2003, 278, 6516-6520.
33. Tenev, T.; Keilhack, H.; Tomic, S.; Stoyanov, B.; Stein-Gerlach, M.; Lammers, R.; Krivtsov, A. V.; Ullrich, A.; Böhmer, F. D. Both SH2 domains are involved in interaction of SHP-1 with the epidermal growth factor receptor but cannot confer receptor-directed activity to SHP-1/SHP-2 chimera. J. Biol. Chem. 1997, 272, 5966-5973.
34. O'Reilly, A. M.; Neel, B. G. Structural determinants of SHP-2 function and specificity in Xenopus mesoderm induction. Mol. Cell. Biol. 1998, 18, 161-177.
35. Yang, J.; Liang, X.; Niu, T.; Meng, W.; Zhao, Z.; Zhou, G. W. Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1. J. Biol. Chem. 1998, 273, 28199-28207.
36. The NCI Diversity set was obtained from the Developmental Therapeutics Program of the NCI/NIH. NSC refers to National Service Center. See the following: Milne, G. W. A.; Feldman, A.; Miller, J. A.; Daly, G. P.; Hammel, M. J. The NCI Drug Information System. 2. DIS pre-registry. J. Chem. Inf. Comput. Sci. 1986, 26, 159-168.
37. Fong, T. A. T.; Shawver, L. K.; Sun, L.; Tang, C.; App, H.; Powell, T. J.; Kim, Y. H.; Schreck, R.; Wang, X.; Risau, W.; Ullrich, A.; Hirth, K. P.; McMahon, G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 1999, 59, 99-106.
38. Sun, L.; Tran, N.; Liang, C.; Tang, F.; Rice, A.; Schreck, R.; Waltz, K.; Shawver, L. K.; McMahon, G.; Tang, C. Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. J. Med. Chem. 1999, 42, 5120-5130.
39. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 2004, 47, 1739-1749.
40. Andersen, J. N.; Mortensen, O. H.; Peters, G. H.; Drake, P. G.; Iversen, L. F.; Olsen, O. H.; Jansen, P. G.; Andersen, H. S.; Tonks, N. K.; Møller, N. P. Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol. Cell. Biol. 2001, 21, 7117-7136.
41. Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.; Nadeau, D. P.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Ryan, M. D.; Levy, M. A.; Keller, P. M.; DeWolf, W. E., Jr. Potent and selective nonpeptide inhibitors of caspases 3 and 7. J. Med. Chem. 2001, 44, 2015-2026.
42. Parrick, J.; Yahya, A.; Ijaz, A. S.; Yizun, J. Convenient preparation of 3,3-dibromo-1,3-dihydroindol-2-ones andindole-2,3-diones (isatins) from indoles. J. Chem. Soc., Perkin Trans. 1 1989, 2009-2015.
43. Bramson, H. N.; Corona, J.; Davis, S. T.; Dickerson, S. H.; Edelstein, M.; Frye, S. V.; Gampe, R. T., Jr.; Harris, P. A.; Hassell, A.; Holmes, W. D.; Hunter, R. N.; Lackey, K. E.; Lovejoy, B.; Luzzio, M. J.; Montana, V.; Rocque, W. J.; Rusnak, D.; Shewchuk, L.; Veal, J. M.; Walker, D. H.; Kuyper, L. F. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J. Med. Chem. 2001, 44, 4339-4358.
44. (a) Gee, K. R.; Sun, W.-C.; Bhalgat, M. K.; Upson, R. H.; Klaubert, D. H.; Latham, K. A.; Haugland, R. P. Fluorogenic substrates based on fluorinated umbelliferones for continuous assays of phosphatases and β-galactosidases. Anal. Biochem. 1999, 273, 41-48.
45. (b) Montalibet, J.; Skorey, K. I.; Kennedy, B. P. Protein tyrosine phosphatase: enzymatic assays. Methods 2005, 35, 2-8.
46. Chu, W.; Zhang, J.; Zeng, C.; Rothfuss, J.; Tu, Z.; Chu, Y.; Reichert, E., D.; Welch, J. M.; Mach, H. R. N-Benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity and molecular modeling studies. J. Med. Chem., 2005, 48, 7637-7647.
47. Somasekhara, S.; Dighe, V. S.; Suthar, G. K.; Mukherjee, S. L. Chlorosulphonation of isatins. Curr. Sci. 1965, 34, 508.