Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines

Journal of Medicinal Chemistry

Volumn 50, Issue 10, 2007, Pages 2341-2351

  Fish, Paul V ^a   Barber, Christopher G ^a   Brown, David G ^a   Butt, Richard ^a   Collis, Michael G ^a   Dickinson, Roger P ^a   Henry, Brian T ^a   Horne, Valerie A ^a   Huggins, John P ^a   King, Elizabeth ^a   O'Gara, Margaret ^a   McCleverty, Dawn ^a   McIntosh, Fraser ^a   Phillips, Christopher ^a   Webster, Robert ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 (7 SULFONAMIDOISOQUINOLINYL)GUANIDINE; 1 [[(4 CHLORO 1 GUANIDINO 7 ISOQUINOLINYL)SULFONYL]AMINO]ISOBUTYRIC ACID METHYL ESTER; 2 [[(4 CHLORO 1 GUANIDIN 7 ISOQUINOLINYL)SULFONYL]AMINO]ISOBUTYRIC ACID; 4 CHLORO 7 (3 CARBOXYPHENYL)ISOQUINOLIN 1 YL)GUANIDINE; AMINO ACID; ESTER DERIVATIVE; GUANIDINE DERIVATIVE; ISOBUTYRIC ACID DERIVATIVE; METHYL 2 [[(1,4 DICHLORO 7 ISOQUINOLINYL)SULFONYL]AMINO]ISOBUTYRATE; N [(1,4 DICHLORO 7 ISOQUINOLINYL)SULFONYL] DEXTRO PROLINE TERT BUTYLESTER; N [(4 CHLORO 1 GUANIDINO 7 ISOQUINOLINYL)SULFONYL] DEXTRO PROLINE; N [(4 CHLORO 1 GUANIDINO 7 ISOQUINOLINYL)SULFONYL] DEXTRO PROLINE TERT BUTYLESTER; PLASMIN; PLASMINOGEN ACTIVATOR INHIBITOR; SULFONAMIDE; UK 371804; UNCLASSIFIED DRUG; UROKINASE;

ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CRYSTALLIZATION; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVITY; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; SKIN ULCER; WOUND FLUID; WOUND HEALING; X RAY CRYSTALLOGRAPHY;

ACUTE DISEASE; ANIMALS; ANTI-ULCER AGENTS; BINDING SITES; CHRONIC DISEASE; CRYSTALLOGRAPHY, X-RAY; GUANIDINES; HUMANS; MODELS, MOLECULAR; PROTEIN BINDING; QUINOLINES; SKIN; SKIN DISEASES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; SWINE; ULCER; URINARY PLASMINOGEN ACTIVATOR; WOUND HEALING;

EID: 34248992886     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm061066t     Document Type: Article

References (34)

1. Epstein, F. H. Cutaneous wound healing. New Eng. J. Med. 1999, 341, 738-746.
2. Frankenne, F.; Noel, A.; Bajou, K.; Sommi, N. E.; Goffin, F.; Musson, V.; Munaut, C.; Remacle, A.; Foidart, J. M. Molecular interactions interactions urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), as new targets for tumour therapy. Emerg. Ther. Targets 1999, 3, 469-481.
3. Stacey, M. C.; Burnand, K. G.; Mahmoud-Alexandroni, M.; Gaffney, P. J.; Bhogal, B. S. Tissue and urokinase plasminogen activators in the environs of venous and ischaemic leg ulcers. Br. J. Surg. 1993, 80, 596-599.
4. Palolahti, M.; Lauharanta, J.; Stephens, R. W.; Kuusela, P.; Vaheri, A. Proteolytic activity in leg ulcer exudate. Exp. Dermatol. 1993, 2, 29-37.
5. Rogers, A. A.; Burnett, S.; Moore, J. C.; Shakespeare, P. G.; Chen, W. Y. J. Involvement of proteolytic enzymes - plasminogen activators and matrix metalloproteinases - in the pathology of pressure ulcers. Wound Rep. Reg. 1995, 3, 273-283.
6. Rogers, A. A.; Burnett, S.; Lindholm, C.; Bjellerup, M.; Christensen, O. B.; Zederfeldt, B.; Peschen, M.; Chen, W. Y. J. Expression of tissue-type and urokinase-type plasminogen activator activities in chronic venous leg ulcers. VASA. J. Vasc. Dis. 1999, 28, 101-105.
7. Wysocki, A. B.; Kusakabe, A. O.; Chang, S.; Tuan, T.-L. Temporal expression of urokinase plasminogen activator and gelatinase-B in chronic wound fluid switches from a chronic to acute profile with progression to healing. Wound Rep. Reg. 1999, 7, 154-165.
8. For reviews see: (a) Steinmetzer, T. Synthetic urokinase inhibitors as potential antitumor drugs. IDrugs 2003, 6, 138-146.
9. (b) Sturzebecher, J.; Schweinitz, A.; Schmalix, W. A.; Wikstrom, P. Synthetic urokinase inhibitors as potential anti-invasive drugs IDrugs 2001, 4, 677-683.
10. (c) Magill, C.; Katz, B. A.; Mackman, R. L. Emerging therapeutic targets in oncology: urokinase-type plasminogen activator system. Emerg. Ther. Targets 1999, 3, 109-133.
11. Geratz, J. D.; Shaver, S. R.; Tidewell, R. R. Inhibitory effect of amidino-substituted heterocyclic compounds on the amidase activity of plasmin and high and low molecular urokinase and on urokinase-induced plasminogen activation. Thromb. Res. 1981, 24, 73-83.
12. Bridges, A. J.; Lee, A.; Schwartz, E.; Towle, M. J.; Littlefield, B. A. The synthesis of three 4-substituted benzo[b]thiophene-2-carboxamides as potent and selective inhibitors of urokinase. Bioorg. Med. Chem. 1993, 1, 403-410.
13. Wendt, M. D.; Geyer, A.; McClellan, W. J.; Rockway, T. W.; Weitzberg, M.; Zhao, X.; Mantei, R.; Stewart, K.; Nienaber, V.; Klinghofer, V.; Giranda, V. L. Interaction with the Slb-pocket of urokinase: 8-heterocycle substituted and 6.8-disubstituted 2-naphthamidine urokinase inhibitors Bioorg. Med. Chem. Lett. 2004, 14, 3063-3068.
14. Vassalli, J.-D.; Belin, D. Amiloride selectively inhibits the urokinase-type plasminogen activator. FEBS Lett. 1987, 214, 187-191.
15. Yang, H.; Henkin, J.; Kim, K. H.; Greer, J. Selective inhibition of urokinase by substituted phenylguanidines: quantitative structure-activity relationship analyses. J. Med. Chem. 1990, 33, 2956-2961.
16. Barber, C. G.; Dickinson, R. P.; Fish, P. V. Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-Isoquinolinylguanidines. Bioorg. Med. Chem. Lett. 2004, 14, 3227-3230.
17. Eloy, F.; Deryckere, A. Synthese d'isocarbostyriles et de chloro-1-isoquinoleines. Helv. Chim. Acta 1969, 52, 1755-1761.
18. Kawazoe, Y.; Yoshioka, Y. Studies on hydrogen exchange IX. Electrophilic deuteration of 2-pyridinol, 2-quinolinol and 1-isoquinolinol. Chem. Pharm. Bull. 1968, 16, 715-720.
19. Barber, C. G.; Dickinson, R. D.; Horne, V. A. Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-Pyridinylguanidines. Bioorg. Med. Chem. Lett. 2002, 12, 181-184.
20. Barber, C. G.; Dickinson, R. D. Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 2: (3-Substituted-5-halo-2-pyridinylguanidines. Bioorg. Med. Chem. Lett. 2002, 12, 185-187.
21. Spraggon, G.; Phillips, C.; Nowak, U. K.; Ponting, C. P.; Saunders, D.; Dobson, C. M.; Stuart, D. I.; Jones, E. Y. The crystal structure of the catalytic domain of human urokinase-type plasminogen activator. Structure 1995, 3, 681-691. Available in the Brookhaven Protein Data Bank as pdb llmw.ent.
22. For reviews see: (a) Sanderson, P. E. J. Small, noncovalent serine protease inhibitors. Med. Res. Rev. 1999, 19, 179-197.
23. (b) Vacca, J. P. New advances in the discovery of thrombin and factor Xa inhibitors. Curr. Opin. Chem. Biol. 2000, 4, 394-400.
24. Sloan, K. B.; Wasdo, S. Designing for topical delivery: prodrugs can make the difference. Med. Res. Rev. 2003, 23, 763-793.
25. Benson, H. A. E. Transdermal drug delivery: Penetration enhancement techniques. Curr. Drug Delivery 2005, 2, 23-33.
26. Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. Haemostasis and Thrombosis. In Pharmacology, 5th ed.: Elsevier: New York, 2003; pp 314-329.
27. Danilewicz, J. C.; Abel, S. M.; Brown, A. D.; Fish, P. V.; Hawkeswood, E.; Holland, S. J.; James, K.; McElroy, A. B.; Overington, J.; Powling, M. J.; Rance, D. J. Design of Selective Thrombin Inhibitors Based on the D-Phe-Pro-Arg Sequence. J. Med Chem. 2002, 45, 2432-2453.
28. Singer, A. J.; McClain, S. A. Development of a porcine excisional wound model. Acad. Emerg. Med. 2003, 10, 1029-1033.
29. Watcher, M. A.; Wheeland, R. G.: The role of topical agents in the healing of full-thickness wounds. J. Dermatol. Surg. Oncol. 1989. 15, 1188-1195.
30. Nienaber, V. L.; Davidson, D.; Edalji, R.; Giranda, V. L.; Klinghofer, V.; Henkin, J. Structure-directed discovery of potent non-peptidic inhibitors of human urokinase that access a novel binding subsite. Struct. Fold. Des. 2000, 8, 553-563.
31. Zeslawska, E.; Schweinitz, A.; Karcher, A.; Sondermann, P.; Sperl, S.; Strurzcbecker, J.; Jacob, U. Crystals of the urokinase type plasminogen activator variant bc-uPA in complex with small molecule inhibitors open the way towards structure based drug design. J. Mol. Biol. 2000, 301, 465-475.
32. Zeslawska, E.; Jacob, U.; Schweinitz, A.; Coombs, G.; Bode, W.; Madison, E. Crystals of the urokinase type plasminogen activator complexes reveal the binding mode of peptidomimetic inhibitors. J. Mol. Biol. 2003, 328, 109-118.
33. Katz, B. A.; Sprengeler, P. A.; Luong, C.; Verner, E.; Elrod, K.; Kirtley, M.; Janc, J.; Spencer, J. R.; Breitenbucher, J. G.; Hui, H.; McGee, D.; Allen, D.; Martelli, A.; Mackman, R. L. Engineering inhibitors highly selective for the SI sites of Ser190 trypsin-like serine protease drug targets. Chem. Biol. 2001, 8, 1107-1121.
34. Stopher, D.; McClean, S. An Improved Method for the Determination of Distribution Co-efficient. J. Pharm. Pharmacol. 1990, 42, 144.