Discovery of pyridyl bis(oxy)dibenzimidamide derivatives as selective matriptase inhibitors

ACS Medicinal Chemistry Letters

Volumn 4, Issue 12, 2013, Pages 1152-1157

  Goswami, Rajeev ^a   Mukherjee, Subhendu ^a   Wohlfahrt, Gerd ^b   Ghadiyaram, Chakshusmathi ^a   Nagaraj, Jwala ^a   Chandra, Beeram Ravi ^a   Sistla, Ramesh K ^a   Satyam, Leena K ^a   Samiulla, Dodheri S ^a   Moilanen, Anu ^b   Subramanya, Hosahalli S ^a   Ramachandra, Murali ^a  

^a Aurigene Discovery Technologies Limited   (India)

^b ORION CORPORATION   (Finland)

Author keywords

cancer; crystal structure; Matriptase; pyridyl dibenzimidamide; SAR

Indexed keywords

AMIDE; SERINE PROTEINASE INHIBITOR;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG CYTOTOXICITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; LIVER MICROSOME; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 84890463218     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400213v     Document Type: Article

References (27)

1. Coghlin, C.; Murray, G. I. Current and emerging concepts in tumour metastasis J. Pathol. 2010, 222, 1-15
2. Duffy, M. J. Do proteases play a role in cancer invasion and metastasis? Eur. J. Cancer Clin. Oncol. 1987, 23, 583-589
3. Liotta, L. A.; Stetler-Stevenson, W. G. Tumor invasion and metastasis: An imbalance of positive and negative regulation Cancer Res. 1991, 51, 5054s-5059s
4. Deryugina, E. I.; Quigley, J. P. Matrix metalloproteinases and tumor metastasis Cancer Metastasis Rev. 2006, 25, 9-34
5. Bonfil, R. D.; Cher, M. L. The role of proteolytic enzymes in metastatic bone disease IBMS BoneKEy 2011, 8, 16-36
6. Naglich, J. G.; Jure-Kunkel, M.; Gupta, E.; Fargnoli, J.; Henderson, A. J.; Lewin, A. C.; Talbott, R.; Baxter, A.; Bird, J.; Savopoulos, R.; Wills, R.; Kramer, R. A.; Trail, P. A. Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-27529 Cancer Res. 2001, 61, 8480-8485
7. Ertongur, S.; Lang, S.; Mack, B.; Wosikowski, K.; Muehlenweg, B.; Gires, O. Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system Int. J. Cancer 2004, 110, 815-824
8. Steinmetzer, T.; Schweinitz, A.; Stürzebecher, A.; Dönnecke, D.; Uhland, K.; Schuster, O.; Steinmetzer, P.; Müller, F.; Friedrich, R.; Than, M. E.; Bode, W.; Stürzebecher, J. Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase J. Med. Chem. 2006, 49, 4116-4126
9. List, K.; Haudenschild, C. C.; Szabo, R.; Chen, W.; Wahl, S. M.; Swaim, W.; Engelholm, L. H.; Behrendt, N.; Bugge, T. H. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis Oncogene 2002, 21, 3765-3779
10. Hooper, J. D.; Clements, J. A.; Quigley, J. P.; Antalis, T. M. Type II transmembrane serine proteases J. Biol. Chem. 2001, 276, 857-860
11. Tsui, K. H.; Chang, P. L.; Feng, T. H.; Chung, L. C.; Hsu, S. Y.; Juang, H. H. Down-regulation of matriptase by overexpression of bikunin attenuates cell invasion in prostate carcinoma cells Anticancer Res. 2008, 28, 1977-1983
12. List, K.; Bugge, T. H.; Szabo, R. Matriptase: potent proteolysis on the cell surface Mol. Med. 2006, 12, 1-7
13. Milner, J. M.; Patel, A.; Davidson, R. K.; Swingler, T. E.; Désilets, A.; Young, D. A.; Kelso, E. B.; Donell, S. T.; Cawston, T. E.; Clark, I. M.; Ferrell, W. R.; Plevin, R.; Lockhart, J. C.; Leduc, R.; Rowan, A. D. Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis Arthritis Rheum. 2010, 61, 1955-1966
14. Netzel-Arnett, S.; Buzza, M. S.; Shea-Donohue, T.; Désilets, A.; Leduc, R.; Fasano, A.; Bugge, T. H.; Antalis, T. M. Matriptase protects against experimental colitis and promotes intestinal barrier recovery Inflamm. Bowel Dis. 2012, 18, 1303-1314
15. Beaulieu, A.; Gravel, é.; Cloutier, A.; Marois, I.; Colombo, é.; Désilets, A.; Verreault, C.; Leduc, R.; Marsault, é.; Richter, M. V. Matriptase proteolytically activates influenza virus and promotes multicycle replication in the human airway epithelium J. Virol. 2013, 87, 4237-4251
16. Baron, J.; Tarnow, C.; Mayoli-Nüssle, D.; Schilling, E.; Meyer, D.; Hammami, M.; Schwalm, F.; Steinmetzer, T.; Guan, Y.; Garten, W.; Klenk, H. D.; Böttcher-Friebertshäuser, E. Matriptase, HAT, and TMPRSS2 activate the hemagglutinin of H9N2 influenza A viruses J. Virol. 2013, 87, 1811-1820
17. Mika, S.; Hiroshi, K.; Naohiro, K.; Yasushi, S.; Mitsuaki, S.; Chen-Yong, L.; Robert, B. D.; Toshihiko, T. Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound Pro-urokinase J. Biol. Chem. 2004, 279, 14899-14908
18. Sheau-Ling, L.; Robert, B. D.; Chen-Yong, L. Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease J. Biol. Chem. 2000, 275, 36720-36725
19. Enyedy, I. J.; Lee, S. L.; Kuo, A. H.; Dickson, R. B.; Lin, C. Y.; Wang, S. Structure-based approach for the discovery of bis-benzamidines as novel inhibitors of matriptase J. Med. Chem. 2001, 44, 1349-1355
20. Schweinitz, A.; Dönnecke, D.; Ludwig, A.; Steinmetzer, P.; Schulze, A.; Kotthaus, J.; Wein, S.; Clement, B.; Steinmetzer, T. Incorporation of neutral C-terminal residues in 3-amidinophenylalanine-derived matriptase inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 1960-1965
21. Colombo, é.; Désilets, A.; Ducheîne, D.; Chagnon, F.; Najmanovich, R.; Leduc, R.; Marsault, E. Design and synthesis of potent, selective inhibitors of matriptase ACS Med. Chem. Lett. 2012, 3, 530-534
22. Friedrich, R.; Fuentes-Prior, P.; Ong, E.; Coombs, G.; Hunter, M.; Oehler, R.; Pierson, D.; Gonzalez, R.; Huber, R.; Bode, W.; Madison, E. L. Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase J. Biol. Chem. 2002, 277, 2160-2168
23. Phillips, G.; Davey, D. D.; Eagen, K. A.; Koovakkat, S. K.; Liang, A.; Ng, H. P.; Pinkerton, M.; Trinh, L.; Whitlow, M.; Beatty, A. M.; Morrissey, M. M. Design, synthesis, and activity of 2,6-diphenoxypyridine-derived factor Xa inhibitors J. Med. Chem. 1999, 42, 1749-1756
24. Friedrich, R.; Steinmetzer, T.; Huber, R.; Stürzebecher, J.; Bode, W. The methyl group of N (alpha)(Me)Arg-containing peptides disturbs the active-site geometry of thrombin, impairing efficient cleavage J. Mol. Biol. 2002, 316, 869-874
25. Maignan, S.; Guilloteau, J. P.; Pouzieux, S.; Choi-Sledeski, Y. M.; Becker, M. R.; Klein, S. I.; Ewing, W. R.; Pauls, H. W.; Spada, A. P.; Mikol, V. Crystal structures of human factor Xa complexed with potent inhibitors J. Med. Chem. 2000, 43, 3226-3232
26. WaterMap, version 1.2; Schrödinger, LLC: New York, 2012.
27. Brodney, M. A.; Barreiro, G.; Ogilvie, K.; Hajos-Korcsok, E.; Murray, J.; Vajdos, F.; Ambroise, C.; Christoffersen, C.; Fisher, K.; Lanyon, L.; Liu, J.; Nolan, C. E.; Withka, J. M.; Borzilleri, K. A.; Efremov, I.; Oborski, C. E.; Varghese, A.; O'Neill, B. T. Spirocyclic sulfamides as -secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer's disease: Utilization of structure based drug design, WaterMap, and CNS penetration studies to identify centrally efficacious inhibitors J. Med. Chem. 2012, 55, 9224-9239