Recent developments in the design of mechanism-based and alternate substrate inhibitors of serine proteases

Current Topics in Medicinal Chemistry

Volumn 4, Issue 12, 2004, Pages 1203-1216

  Zhong, Jiaying ^a   Groutas, Wiliam C ^a  

^a WICHITA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 OXACEPHEM DERIVATIVE; 2 AZETIDINONE DERIVATIVE; 5,6 DIHYDROURACIL DERIVATIVE; ANTIVIRUS AGENT; ASPARTIC PROTEINASE; AZETIDINE DERIVATIVE; BACTERIAL ENZYME; BENZOXAZINE DERIVATIVE; BETA LACTAM; CATHEPSIN G; CEPHALOSPORIN DERIVATIVE; CHYMASE; CHYMOTRYPSIN A; COUMARIN; CYSTEINE PROTEINASE; HYDANTOIN DERIVATIVE; IMIDAZOLE DERIVATIVE; LACTONE DERIVATIVE; LEUKOCYTE ELASTASE; LEUKOCYTE ELASTASE INHIBITOR; METALLOPROTEINASE; OXAZOLONE; PHTHALIMIDE DERIVATIVE; PROSTATE SPECIFIC ANTIGEN; PYRROLIDINE DERIVATIVE; SERINE PROTEINASE; SERINE PROTEINASE INHIBITOR; SUCCINIMIDE DERIVATIVE; UNINDEXED DRUG; VIRUS ENZYME;

CHEMICAL MODIFICATION; COVALENT BOND; DRUG DESIGN; DRUG MECHANISM; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME SUBSTRATE; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN FAMILY; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; DRUG DESIGN; HUMANS; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS;

EID: 4444380663     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/1568026043387971     Document Type: Review

References (140)

1. Proteolytic Enzymes; Beynon, R.; Bond, J. S.; Eds.; 2nd ed., Oxford University Press: Oxford, 2001.
2. Blatt, N. B.; Glick, G. D. Signaling Pathways and Effector Mechanisms. Pre-Programmed Cell Death. Bioorg. Med. Chem. 2001, 9, 1371-1384.
3. Potempa, J.; Korzua, E.; Travis, J. The Serpin Superfamily of Proteinase Inhibitors: Structure, Function, and Regulation. J. Biol. Chem. 1994, 269, 15957-15960.
4. Gettins, P. G.; Patson, P. A.; Olson, S. T. Serpins: Structure, Function, and Biology; Landes Biosciences: New York, 1996.
5. Turk, B.; Turk, V.; Turk, D. Structural and Functional Aspects of Papain-like Cysteine Proteinases and Their Protein Inhibitors. Biol. Chem. 1997, 378, 141-150.
6. Woessner, J. F.; Nagase, H. Matrix Metalloproteinases and TIMPS; Oxford University Press: New York, 2000.
7. Leung, D.; Abbenante, G.; Fairlie, D. P. Protease Inhibitors: Current Status and Future Prospects. J. Med. Chem. 2000, 43, 305-341.
8. Babine, R. E.; Bender, S. L. Molecular Recognition of Protein-Ligand Complexes. Chem. Revs. 1997, 97, 1359-1472.
9. Thomson, L. A.; Tebben, A. J. Pharmacokinetics and Design of Aspartyl Protease Inhibitors. Ann. Rep. Med. Chem. 2001, 36, 247-256.
10. Marquis, R. W. Inhibition of Cysteine Proteases. Ann. Rep Med. Chem. 2000, 35, 309-320.
11. Leung-Toung, R.; Li, W.; Tam, T. F.; Karimian, K. Thiol-Dependent Enzymes and Their Inhibitors. Curr. Med. Chem. 2002, 9, 979-1002.
12. Whittaker, M.; Floyd, C. D.; Brown, P.; Gearing, A. J. H. Design and Therapeutic Application of Matrix Metalloproteinase Inhibitors. Chem. Revs. 1999, 97, 1359-1472.
13. Coussens, L. M.; Fingleton, B.; Matrisian, L. M. Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations. Science. 2002, 295, 2387-2392.
14. Sanderson, P. E. J. Anticoagulants: Inhibitors of Thrombin and Factor Xa Ann. Rep. Med. Chem. 2001, 36, 79-88.
15. Metz, W. A.; Peet, N. P. Inhibitors of Human Neutrophil Elastase as a Potential Treatment for Inflammatory Diseases. Exp. Opin. Ther. Patents. 1999, 9, 851-868.
16. Skiles, J. W.; Jeng, A. Y. Therapeutic Promises of Leukocyte Elastase and Macrophage Metalloelastase Inhibitors for the Treatment of Pulmonary Emphysema. Exp. Opin. Ther. Patents. 1999, 9, 865-895.
17. Maly, D. J.; Huang, L.; Ellman, J. A. Combinatorial Strategies for Targeting Protein Families: Application to the Proteases. ChemBiochem. 2002, 3, 16-37.
18. Silverman, R. B. The Organic Chemistry of Enzyme-Catalyzed Reactions; Academic Press: San Diego, 2000, Ch. 2.
19. Wilmouth, R. C.; Edman, K.; Neutze, R.; Wright, P. A.; Clifton, I. J.; Schneider, T. R.; Schofield, C. J.; Hajdu, J. X-ray Snapshots of Serine Protease Catalysis Reveal a Tetrahedral Intermediate. Nature Struct. Biol. 2001, 8, 689-694.
20. Sperl, S.; Jacob, U.; De Prada, A. A.; Strurzebecher, J; Wilhelm, O. G.; Bode, W.; Magdolen, V.; Huber, R.; Moroder, L. (4-Aminomethyl)phenylguanidine Derivatives as Nonpeptidic Highly Selective Inhibitors of Human Urokinase. Proc. Natl. Acad. Sci. USA, 2000, 97, 5113-5118.
21. Burgess, K. Solid-Phase Syntheses of β-Turn Analogues to Mimic or Disrupt Protein-Protein Interactions. Acc. Chem. Res. 2001, 34, 826-835 and references cited therein,
22. Bursavitch, M. G.; Rich, D. H. Designing Non-Peptide Peptidomimetics in the 21st Century: Inhibitors Targeting Conformational Ensembles. J. Med. Chem. 2002, 45, 541-558.
23. Davis, A. M.; Teague, S. J. Hydrophobic Bonding, Hydrophobic Interactions, and Failure of the Rigid Receptor Hypothesis. Angew. Chem. Int. Ed. 1999, 38, 736-749.
24. Silverman, R. B. Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology; CRC Press; Boca Raton, 1988; Vols. 1 & 2.
25. Silverman, R. B. Mechanism-Based Enzyme Inactivators. Meth. Enzymol. 1995, 249, 240-283.
26. Groutas, W. C.; Giri, P. K.; Crowley, J. P.; Castrisos, J. C.; Brubaker, M. J. The Lossen Rearrangement in Biological Systems. Inactivation of Leukocye Elastase and α-Chymotrypsin by (DL)-3-Benzyl-N-(methanesulfonyloxy)succinimide. Biochem. Biophys. Res. Comm. 1986, 141, 741-748.
27. Groutas, W. C.; Brubaker, M. J.; Stanga, M. A.; Castrisos, J. C.; Crowley, J. P.; Schatz, E. J. Inhibition of Human Leukocyte Elastase by Derivatives of N-Hydroxysuccinimide. A Structure-Activity Relationship Study. J. Med. Chem. 1989, 32, 1607-1611.
28. 31P Nuclear Magnetic Resonance Spectroscopy. Biochemistry. 1991, 30, 4132-4136.
29. Groutas, J. C.; Venkataraman, R.; Brubaker, M. J.; Epp, J. B.; Chong, L. S.; Stanga, M. A.; McClenahan, J. J.; Tagusagawa, F. 3-(Alkylthio)-N-hydroxysuccinimide Derivatives: Potent Inhibitors of Human Leukocyte Elastase. Arch. Biochem. Biophys. 1993, 1164, 283-288.
30. Groutas, W. C.; Stanga, M. A.; Castrisos, J. C.; Schatz, E. J. Hydantoin Derivatives. A New Class of Inhibitors of Human Leukocyte Elastase. J. Enz. Inh. 1990, 3, 237-243.
31. Groutas, W. C.; Huang, H.; Epp, J. B.; Venkataraman, R.; McClenahan, J. J.; Tagusagawa, F. Mechanism-Based Inhibition of Human Leukocyte Elastase and Cathepsin G by Substituted Dihydrouracils. Biochim. Biophys. Acta. 1994, 1227, 130-136.
32. Neumann, U.; Gutschow, M. N-(Sulfonyloxy)phthalimides and Analogues are Potent Inactivators of Serine Proteases. J. Biol. Chem. 1994, 269, 21561-21567.
33. Kerrigan, J. E.; Shirley, J. J. 2-[(Alkylsulfonyl)oxy]-6-Substituted-1H-Isoindole-1,3(2H)-Dione. Mechanism-Based Inhibitors of Human Leukocyte Elastase. Bioorg. Med. Chem. Lett. 1996, 6, 451-456.
34. Groutas, W. C.; Castrisos, J. C.; Stanga, M. A.; Kuang, R.; Venkataraman, R.; Epp, J. B.; Brubaker, M. J.; Chong, L. S. Heterocyclic Inhibitors of Human Leukocyte Elastase. 3-Hydroxypyridazopyrimidine, 3-Hydroxypyridopyrimidine and 3-Hydroxyquinazoline-2,4(1H,3H)Dione Derivatives. Bioorg. Med. Chem. Lett. 1993, 3, 1163-1168.
35. 13C NMR Studies for an Enzyme-Induced Lossen Rearrangement in the Mechanism-Based Inactivation of α-Chymotrypsin by 3-Benzyl-N-[(methylsulfonyl)oxy]succinimide. J. Am. Chem. Soc. 1989, 111, 1931-1932.
36. Abell, A. D.; Oldham, M. D. Synthesis and X-ray Crystallographic Structure of Leucine-Phenylalaninyl Succinimide-Based Pseudopeptides. J. Org. Chem. 1997, 62, 1509-1513.
37. Martyn, D. C.; Moore, M. J. B.; Abell, A. D. Succinimide and Saccharin-Based Enzyme-Activated Inhibitors of Serine Proteases Curr. Pharm. Des. 1999, 5, 405-415.
38. Proteases of Infectious Agents; Dunn, B. M.; Ed.; Academic Press: San Diego, 1999.
39. Pinto, I. L.; West, A.; Debouck, C. M.; DiLella, A. G.; Gorniak, J. G.; O'Donnell, K. C.; O'Shannessy, D. J.; Patel, A.; Jarvest, R. L. Novel, Selective Mechanism-Based Inhibitors of the Herpes Proteases. Bioorg. Med. Chem. Lett. 1996, 6, 2467-2472.
40. Vagnoni, L. M.; Gronostaj, M.; Kerrigan, J. E. 6-Acylamino-2-[(ethylsulfonyl)oxy]-1H-isoindole-1,3-diones. Mechanism-Based Inhibitors of Human Leukocyte Elastase and Cathepsin G: Effect of Chirality in the 6-Acylamino Substituent on Inhibitory Potency and Selectivity. Bioorg. Med. Chem. 2001, 9, 637-645.
41. Kerrigan, J. E.; Walters, M. C.; Forrester, K. J.; Crowder, J. B.; Christopher, L. J. 6-Acylamino-2-[(alkylsulfonyl)oxy]-1H-isoindole-1,3-dione. Mechanism-Based Inhibitors of Human Leukocyte Elastase. Biorg. Med. Chem. 2000, 10, 27-30.
42. Hill, J. H. M. Mechanism of the Gabriel-Colman Rearrangement. J. Org. Chem. 1965, 30, 620-622.
43. Groutas, W. C.; Chong, L. S.; Venkataraman, R.; Epp, J. B.; Kuang, R.; Brubaker, M. J.; Houser-Archield, N.; Huang, H.; McClenahan, J. J. Mechanism-Based Inhibitors of Serine Proteinases Based on the Gabriel-Colman Rearragement. Biochem. Biophys. Res. Comm. 1993, 194, 1491-1499.
44. Groutas, W. C.; Chong, L. S.; Venkataraman, R.; Epp, J. B.; Kuang, R.; Houser-Archield, N.; Hoidal, J. R. The Gabriel-Colman Rearrangement in Biological Systems: Design, Synthesis and Biological Evaluation of Phthalimide and Saccharin Derivatives as Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase 3. Bioorg. Med. Chem. 1995, 3, 187-193.
45. Groutas, W. C.; Brubaker, M. J.; Chong, L. S.; Venkataraman, R.; Huang, H.; Epp, J. B.; Kuang, R.; Hoidal, J. R. Design, Synthesis and Biological Evaluation of Succinimide Derivatives as Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase 3. Bioorg. Med. Chem. 1995, 3, 375-381.
46. Groutas, W. C.; Chong, L. S.; Venkataraman, R.; Huang, H.; Epp, J. B.; Kuang, R. A General Approach Toward the Design of Mechanism-Based Inhibitors of Serine Proteinases: Inactivation of Human Leukocyte Elastase by a Phthalimide Derivative. Bioorg. Med. Chem. Lett. 1993, 3, 2745-2750.
47. Groutas, W. C.; Houser-Archield, N.; Chong, L. S.; Venkataraman, R.; Epp, J. B.; Huang, H.; McClenahan, J. J. Efficient Inhibition of Human Leukocyte Elastase and Cathepsin G by Saccharin Derivatives. J. Med. Chem. 1993, 36, 3178-3181.
48. Groutas, W. C.; Huang, H.; Venkataraman, R.; Epp, J. B. Dual Function Inhibitors of Proteolytic Enzymes: Potential Therapeutic Agents for Cystic Fibrosis and Related Ailments. Bioorg. Med. Chem. 1993, 1, 273-277.
49. Groutas, W. C.; Epp, J. B.; Venkataraman, R.; Kuang, R.; Truong, T. M.; McClenahan, J. J. Design, Synthesis and In Vitro Inhibitory Activity Toward Human Leukocyte Elastase, Cathepsin G and Proteinase 3 by Saccharin Sulfones and Congeners. Bioorg. Med. Chem. 1996, 4, 1393-1400.
50. Groutas, W. C.; Chong, L. S.; Venkataraman, R.; Kuang, R.; Epp, J. B.; Houser-Archield, N.; Huang, H.; Hoidal, J. R. Amino Acid-Derived Phthalimide and Saccharin Derivatives as Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase 3 Arch. Biochem. Biophys. 1996, 332, 335-340.
51. Hlasta, D. J.; Subrmanyam, C.; Bell, M. R.; Carbateas, P. M.; Court, J. J.; Desai, R. C.; Drozd, M. L.; Eickhoff, W. M.; Ferguson, E. W.; Gordon, R. J.; Johnson, J. A.; Kumar, V.; Maycock, A. L.; Mueller, K. R.; Pagani, E. D.; Robinson, D. T.; Saindane, M. T.; Silver, P. J.; Subramanian, S.; Dunlap, R. P.; Franke, C. A.; Mura, A. J.; Rowlands, A. G. Orally Bioavailable Benzisothiazolone Inhibitors of Human Leukocyte Elastase. J. Med. Chem. 1995, 38, 739-744 and references cited therein.
52. Groutas, W. C.; Kuang, R.; Venkataraman, R. 3-Oxo-4-Substituted 1,2,5-Thiadiazolidin 1,1 Dioxides: A New Class of Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase. Biochem. Biophys. Res. Comm. 1994, 198, 341-349.
53. Groutas, W. C.; Kuang, R.; Venkataraman, R.; Epp, J. B.; Ruan, S.; Prakash, O. Structure-Base Design of a General Class of Mechanism-Based Inhibitors of Serine Proteinases Employing a Novel Amino Acid-Derived Heterocyclic Scaffold. Biochemistry. 1997, 36, 4739-4750.
54. Groutas, W. C.; Schechter, N. M.; He, S.; Yu, H.; Tu, J. Human Chymase Inhibitors Based on the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide Scaffold. Bioorg. Med. Chem. 1999, 9, 2199-2204.
55. Groutas, W. C.; Chong, L. S.; Venkataraman, R. Novel Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase and Cathepsin G: Derivatives of Isothiazolidin-3-one. Biochem. Biophys. Res. Comm. 1993, 197, 730-739.
56. Kuang, R.; Venkataraman, R.; Ruan, S.; Groutas, W. C. Use of the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide and Isothiazolidin-3-one 1,1 Dioxide Scaffolds in the Design of Potent Inhibitors of Serine Proteinases Bioorg. Med. Chem. Lett. 1998, 8, 539-544.
57. Kuang, R.; Epp, J. B.; Ruan, S.; Chong, L. S.; Venkataraman, R.; Tu, J.; He, S.; Truong, T. M.; Groutas, W. C. Utilization of the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide Scaffold in the Design of Potent Inhibitors of Serine Proteases: SAR Studies Using Carboxylates. Bioorg. Med. Chem. 2000, 8, 1005-1016.
58. Groutas, W. C.; Kuang, R.; Ruan, S.; Epp, J. B.; Venkataraman, R.; Truong, T. M. Potent and Specific Inhibition of Human Leukocyte Elastase, Cathepsin G and Proteinase 3 by Sulfone Derivatives Employing the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide Scaffold Bioorg. Med. Chem. 1998, 6, 661-671.
59. Groutas, W. C.; Epp, J. B.; Kuang, R.; Ruan, S.; Chong, L. S.; Venkataraman, R.; Tu, J.; He, S.; Yu, H.; Fu, Q.; Li, Y-H.; Truong, T. M.; Vu, N. T. 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide: A Powerful Scaffold for Probing the S′ Subsites of (Chymo)trypsin-like Serine Proteases. Arch. Biochem. Biophys. 2001, 385, 162-169.
60. Groutas, W. C.; He, S.; Kuang, R.; Ruan, S.; Tu, J.; Chan, H-K. Inhibition of Serine Proteases by Functionalized Sulfonamides Coupled to the 1,2,5-Thiadiazolidin-3-one 1,1 Dioxide Scaffold. Bioorg. Med. Chem. 2001, 9, 1543-1548.
61. Kuang, R.; Epp, J. B.; Ruan, S.; Yu, H.; Huang, P.; He, S.; Tu, J.; Schechter, N. M.; Turbov, J.; Froelich, C. J.; Groutas, W. C. A Universal Scaffold for Serine Proteases With a (Chymo)trypsin-like Fold: Solution Phase Construction and Evaluation of the First Series of Libraries of Mechanism-Based Inhibitors. J. Am. Chem. Soc. 1999, 121, 8128-8129.
62. Doherty, J. B.; Ashe, B. M.; Argenbright, L. W.; Barker, P. L.; Bonney, R. J.; Chandler, G. O.; Dahlgren, M. E.; Dorn, C. P.; Finke, P. E.; Firestone, R. A.; Fletcher, D.; Hagmann, W. K.; Mumford, R.; O'Grady, L.; Maycock, A. L.; Pisano, J. M.; Shah, S. K.; Thomson, K. R.; Zimmerman, M. Cephalosporin Antibiotics can be Modified to Inhibit Human Leukocyte Elastase. Nature. 1986, 232, 192-194.
63. Shah, S. K.; Dorn, C. P.; Finke, P. E.; Hale, J. J.; Hagman, W. K.; Brause, K. A.; Chandler, G. O.; Kissinger, A. L.; Ashe, B. M.; Weston, H.; Knight, W. B.; Maycock, A. L.; Dellea, P. S.; Fletcher, D. S.; Hand, K. M.; Mumford, R. A.; Underwood, D. J.; Doherty, J. B. Orally Active β-Lactam Inhibitors of Human Leukocyte Elastase. Activity of 3,3-Diethyl-2-azetidinones. J. Med. Chem. 1992, 35, 3745-3754.
64. Aoyama, Y.; Uenaka, M.; Konoike, T.; Iso, Y.; Nishitani, Y.; Kanda, A.; Naya, N.; Nakajima, M. Synthesis and Structure-Activity Relationships of a New Class of 1-Oxacephem-Based Human Chymase Inhibitors. Bioorg. Med. Chem. Lett. 2000, 10, 2397-2401.
65. Aoyama, Y.; Uenaka, M.; Konoike, T.; Iso, Y.; Nishitani, Y.; Kanda, A.; Naya, N.; Nakajima, M. 1-Oxacephem-Based Human Chymase Inhibitors: Discovery of Stable Inhibitors in Human Plasma. Bioorg. Med. Chem. Lett. 2000, 10, 2403-2406.
66. Schechter, N. M.; Pereira, P. J. B.; Stroble, S. Structure and Function of Human Chymase, in Mast Cells and Basophils; Marone, G.; Lichtenstein, L. M.; Galli, S. J.; Eds.; Academic Press: San Diego, 2000, Ch. 18.
67. Kinoshita, A.; Urata, H.; Bumpus, F. M.; Husain, A. Multiple Determinants for the High Substrate Specificity of an Angiotensin II-forming Chymase from the Human Heart. J. Biol. Chem. 1991, 266, 19192-19197.
68. Pereira, P. J. B.; Wang, Z-M.; Rubin, H.; Huber, R.; Bode, W.; Schechter, N. M.; Strobl, S. The 2.2 Å Crystal Structure of Human Chymase in Complex with Succinyl-Ala-Ala-Pro-Phe Chloromethylketone: Structural Explanation for its Dipeptidyl Carboxypeptidase Specificity. J. Mol. Biol. 1999, 286, 163-173.
69. Fukami, H.; Okunishi, H.; Miyazaki, M. Chymase: Its Pathophysiological Roles and Inhibitors. Curr. Pharm. Des. 1998, 4, 439-453.
70. Urata, H.; Nishimura, H.; Ganten, D. Chymase-Dependent Angiotensin II-Forming System in Humans. Am. J. Hypertens. 1996, 9, 277-284.
71. Maruyama, R.; Hatta, E.; Yasuda, K.; Smith, N. C. E.; Levi, R. Angiotensin-Converting Enzyme-Independent Angiotensin Formation in a Human Model of myocardial Ischemia: Modulation of Norepinephrine Release by Angiotensin Type 1 and Angiotensin Type 2 Receptors. J. Pharm. Exp. Ther. 2000, 294, 248-254.
72. Aoyama, Y.; Uenaka, M.; Kii, M.; Tanaka, M.; Konoike, T.; Hayasaki-Kajiwara, Y.; Naya, N.; Nakajima, M. Design, Synthesis and Pharmacological Evaluation of 3-Benzylazetidine-2-one-Based Human Chymase Inhibitors. Bioorg. Med. Chem. 2001, 9, 3065-3075.
73. Adlington, R. M.; Baldwin, J. E.; Becker, G. W.; Chen, B.; Cheng, L.; Cooper, S. L.; Hermann, R. B.; Howe, T. J.; McCoull, W.; McNulty, A. M.; Neubauer, B. L.; Pritchard, G. J. Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen. J. Med. Chem. 2001, 44, 1491-1508.
74. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Puglisi, A. Efficient and Highly Stereoselective Synthesis of a β -Lactam Inhibitor of the Serine Protease Prostate Specific Antigen. Bioorg. Med. Chem. 2002, 10, 1813-1818.
75. Coombs, G. S.; Bergstrom, R. C.; Pellequer, J-L.; Baker, S. I.; Navre, M.; Smith, M. M.; Tainer, J. A.; Madison, E. L.; Corey, D. R. Substrate Specificity of Prostate-Specific Antigen. Chem. Biol. 1998, 5, 475-488.
76. Webber, M. M.; Waghray, A.; Bello, D. Prostate Specific Antigen, a Serine Protease, Facilitates Human Prostate Cancer Cell Invasion. Clin. Cancer Res. 1995, 1, 1089-1094.
77. Fortier, A. H.; Nelson, B. J.; Grella, D. K.; Holaday, J. W. Antiangiogenic Activity of Prostate-Specific Antigen. J. Natl. Cancer Inst. 1999, 91, 1635-1640.
78. Borthwick, A. D.; Weingarten, G.; Haley, T. M.; Tomaszewski, M.; Wang, W.; Hu, Z.; Bedard, J.; Jin, H.; Yuen, L.; Mansour, T. S. Design and Synthesis of Monocyclic β-Lactams as Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. Bioorg. Med. Chem. Lett. 1998, 8, 365-370.
79. Deziel, R.; Malenfant, E. Inhibition of Human Cytomegalovirus Protease with Monocyclic β-Lactams. Biorg. Med. Chem. Lett. 1998, 8, 1437-1442.
80. Yoakim, C.; Ogilvie, W. W.; Cameron, D. R.; Chabot, C.; Guse, I.; Hache, B.; Naud, J.; O'Meara, J. A.; Plante, R.; Deziel, R. β -Lactam Derivatives as Inhibitors of Human Cytomegalovirus Protease. J. Med. Chem. 1998, 41, 2882-2891.
81. Pochet, L.; Doucet, C.; Dive, G.; Wouters, J.; Masereel, B.; Reboud-Ravaux, M.; Pirotte, B. Coumarinic Derivatives as Mechanism-Based Inhibitors of α-Chymotrypsin and Human Leukocyte Elastase. Bioorg. Med. Chem. 2000, 8, 1489-1501 and references cited therein.
82. Hernadez, M. A.; Powers, J. C.; Glinski, J.; Oleksyszyn, J.; Vijayalakshmi, J.; Meyers, E. F. Effect of the 7-Amino Substituent on the Inhibitory Potency of Mechanism-Based Isocoumarin Inhibitors for Porcine Pancreatic and Human Neutrophil Elastases: A 1.85 Å X-ray Crystal Structure of the Complex Between Porcine Pancreatic Elastase and 7-[N-Tosylphenylalanyl)amino]-4-chloro-3- methoxyisocoumarin. J. Med. Chem. 1992, 35, 1121-1129 and references cited therein.
83. Doucet, C.; Pochet, L.; Thierry, N.; Pirotte, B.; Delarge, J.; Reboud-Ravaux, M. 6-Substituted 2-Oxo-2H-1-benzopyran-3-carboxylic Acid as a Core Structure for Specific Inhibitors of Human Leukocyte Elastase. J. Med. Chem. 1999, 42, 4161-4171.
84. Xing, R.; Hanzlik, R. P. Azapeptides as Inhibitors and Active Site Titrants for Cysteine Proteinases. J. Med. Chem. 1998, 41, 1344-1351.
85. Zhang, R.; Durkin, J. P.; Windsor, W. T. Azapeptides as Inhibitors of the Hepatitis C Virus NS3 Serine Protease. Bioorg. Med. Chem. Lett. 2002, 12, 1005-1008 and references cited therein.
86. Sykes, N. O.; MacDonald, S. J. F.; Page, M. I. Acylating Agents as Enzyme Inhibitors and Understanding Their Reactivity for Drug Design. J. Med. Chem. 2002, 45, 2850-2856.
87. MacDonald, S. J. F.; Dowle, M. D.; Harrison, L. A.; Spooner, J. E.; Shah, P.; Johnson, M. R.; Inglis, G. G. A.; Clarke, G. D. E.; Belton, D. J.; Smith, R. A.; Molloy, C. R.; Dixon, M.; Murkitt, G.; Godward, R. E.; Skarzynski, T.; Singh, O. M. P.; Kumar, K. A.; Hodgson, S. T.; MacDonald, E.; Hardy, G. W.; Finch, H. Intracellular Inhibition of Human Neutrophil Elastase by Orally Active Pyrrolidine-trans-lactams. Bioorg. Med. Chem. Lett. 2001, 11, 243-246.
88. MacDonald, S. J. F.; Dowle, M. D.; Harrison, L. A.; Shah, P.; Johnson, M. R.; Inglis, G. G. A.; Clarke, G. D. E.; Smith, R. A.; Humphreys, D.; Molloy, C. R.; Amour, A.; Dixon, M.; Murkitt, G.; Godward, R. E.; Padfield, T.; Skarzynski, T.; Singh, O. M. P.; Kumar, K. A.; Fleetwood, G.; Hodgson, S. T.; Hardy, G. W.; Finch, H. The Discovery of a Potent, Intracellular, Orally Bioavailable, Long Duration Inhibitor of Human Neutrophil Elastase - GW311616A, a Development Candidate. Bioorg. Med. Chem. Lett. 2001, 11, 895-898.
89. Borthwick, A. D.; Crame, A. J.; Ertl, P. F.; Exall, A. M.; Haley, T. M.; Hart, G. J.; Mason, A. M.; Pennell, A. M. K.; Singh, O. M. P.; Weingarten, G. G.; Woolven, J. M. Design and Synthesis of Pyrrolidine-5,5-trans-lactams(5-Oxohexahydropyrrolo [3.2-b] pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. Potency and Chirality. J. Med. Chem. 2002, 45, 1-18.
90. Borthwick, A. D.; Exall, A. M.; Haley, T. M.; Jackson, D. L.; Mason, A. M.; Weingarten, G. G. Pyrrolidine-5,5-trans-lactams as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Proteases. Potency and Plasma Stability. Bioorg. Med. Chem. 2002, 12, 1719-1722.
91. Gutschow, M.; Neumann, U.; Sieler, J.; Eger, K. Studies on 2-Benzyloxy-4H-3,1-benzoxazin-4-ones as Serine Protease Inhibitors. Pharm. Acta Helv. 1998, 73, 426-428 and references cited therein.
92. Gutschow, M.; Neumann, U. Inhibition of Cathepsin G by 4H-3,1-Benzoxazin-3-ones. Bioorg. Med. Chem. Lett. 1997, 5, 1935-1942.
93. Neumann, U.; Schechter, N. M.; Gutschow, M. Inhibition of Human Chymase by 2-Amino-3,1-benzoxazin-4-ones. Biorg. Med. Chem. 2001, 9, 947-954.
94. Jarvest, R. L.; Parratt, M. J.; Debouck, C. M.; Gorniak, J. G.; Jennings, L. J.; Serafinowska, H. T.; Strickler, J. E. Inhibition of HSV-1 Protease by Benzoxazinones. Bioorg. Med. Chem. Lett. 1996, 6, 2463-2466.
95. Abood, N. A.; Schretzman, L. A.; Flynn, D. L.; Houseman, K. A.; Wittwer, A. J.; Dilworth, V. M.; Hippenmeyer, P. J.; Holwerda, B. C. Inhibition of Human Cytomegalovirus Protease by Benzoxazinones and Evidence of Antiviral Activity in Cell Culture. Bioorg. Med. Chem. Lett. 1997, 7, 2105-2108.
96. Flynn, D. L.; Abood, N. A.; Holweda, B. C. Recent Advances in Antiviral Research: Identification of Inhibitors of the Herpesvirus Proteases. Chem. Biol. 1997, 1, 190-196.
97. Gutschow, M.; Kuerschner, L.; Pietsch, M.; Loser, R.; Koglin, N.; Eger, K. 2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase. J. Med. Chem. 1999, 42, 5437-5447.
98. Gutschow, M.; Neumann, U. Novel Thieno[2,3-d][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase. J. Med. Chem. 1998, 41, 1729-1740.
99. Jarvest, R. L.; Connor, S. C.; Gorniak, J. G.; Jennings, L. J.; Serafinowska, H.; West, A. Potent Selective Thienoxazinone Inhibitors of Herpes Proteases. Bioorg. Med. Chem. Lett. 1997, 7, 1733-1738.
100. Jarvest, R. L.; Pinto, I. L.; Ashman, S. M.; Debrowski, C. E.; Fernadez, A. V.; Jennings, L. J.; Lavery, P.; Tew, D. G. Inhibition of Herpes Proteases and Antiviral Activity of 2-Substituted Thieno[2,3-d]oxazinones. Bioorg. Med. Chem. Lett. 1999, 9, 443-448.
101. Pinto, I. L.; Jarvest, R. L.; Clarke, B.; Dabrowski, C. E.; Fenwisk, A.; Gorczyca, M. M.; Jennings, L. J.; Lavery, P.; Sternberg, E. J.; Tew, D. G.; West, A. Inhibition of Human Cytomegalovirus Protease by Enedione Derivatives of Thieno[2,3-d]Oxazinones Through a Novel Dual Acylation/Alkylation Mechanism. Bioorg. Med. Chem. Lett. 1999, 9, 449-452.
102. Aoyama, Y.; Uenaka, M.; Konoike, T.; Hayasaki-Kajiwara, Y.; Naya, N.; Nakajima, M. Inhibition of Serine Proteases: Activity of 1,3-Diazetidine-2,4-ones. Bioorg. Med. Chem. Lett. 2001, 11, 1691-1694.
103. Ito, K.; Igarashi, K.; Muramatsu, M.; Harada, T.; Hayashi, Y.; Katada, J.; Uno, I. Potent Inactivator of α-Chymotrypsin: 2,2-Dimethyl-3-(N-4-Cyanobenzoyl) amino-5-phenyl Pentanoic Acid. Biochem. Biophys. Res. Comm. 1997, 240, 850-855.
104. Ijima, K.; Katada, J.; Yasuda, E.; Uno, I.; Hayashi, Y. N-[2,2-Dimethyl-3-[N(4-cyanobenzoyl)amino)momamoyl]-L-phenylalanine Ethyl Ester as a Stable Ester-Type Inhibitor of α-Chymotrypsin-like Serine Proteases: Structural Requirements for Potent Inhibition of α-Chymotrypsin. J. Med. Chem. 1999, 42, 312-323.
105. Reid, P. T.; Sallenave, J. M. Neutrophil-Derived Elastases and Their Inhibitors: Potential Role in the Pathogenesis of Lung Disease. Curr. Opin. Investig Drugs. 2002, 2, 59-67.
106. Ohbayashi, H. Neutrophil Elastase Inhibitors as Treatment for COPD Expert Opin. Investig Drugs. 2002, 11, 965-980.
107. Campbell, E. J.; Campbell, M. A.; Owen, C. A. Bioactive Proteinase 3 on the Cell Surface of Human Neutrophils: Quantification, Catalytic Activity, and Susceptibility to Inhibition. J. Immunol. 2000, 165, 3366-3374.
108. Greco, M. N.; Hawkins, M. J.; Powell, E. T.; Almond, H. R.; Corcoran, T. W.; de Caravilla, L.; Kauffman, J. A.; Recacha, R.; Chattopadhyay, D.; Andrade-Gordon, P.; Maryanoff, B. E. Nonpeptide Inhibitors of Cathepsin G: Optimization of a Novel β-Ketophosphonic Acid Lead by Structure-Based Drug Design. J. Am. Chem. Soc. 2002, 17, 3810-3811.
109. Huang, X.; Knoell, C. T.; Frey, G.; Hazegh-Azam, M.; Tashjian, A. H.; Hedstrom, L.; Abeles, R. H.; Timasheff, S. N. Modulation of Recombinant Human Prostate-Specific Antigen: Activation by Hofmeister Salts and Inhibition by Azapeptides. Biochemistry. 2001, 40, 11734-11741.
110. Friedrich, R.; Fuentes-Prior, P.; Ong, E.; Coombs, G.; Hunter, M.; Oehlere, R.; Pierson, D.; Gonzalez, R.; Huber, R.; Bode, W.; Madison, E. L. Catalytic Domain Structures of MT-SP1/Matriptase, a Matrix-Degrading Transmembrane Serine Protease. J. Biol. Chem. 2002, 277, 2160-2168.
111. Oberst, M. D.; Johnson, M. D.; Dickson, R. B.; Lin, C. Y.; Singh, B.; Stewart, M.; Williams, A.; al-Nafussi, A.; Smyth, J. F.; Gabra, H.; Sellar, G. C. Expression of the Serine Protease Matriptase and its Inhibitor HAI-1 in Epithelial Ovarian Cancer: Correlation with Clinical Outcome and Tumor Clinicopathological Parameter. Clin Cancer Res. 2002, 8, 1101-1107.
112. Nienaber, V. L.; Davidson, D.; Edalji, R.; Giranda, V. L.; Klinghofer, V.; Henkin, J.; Magdalmos, P.; Mantei, R.; Merrick, J.; Severin, J. M.; Smith, R. A.; Stewart, K.; Walter, K.; Wang, J.; Wendt, M.; Weitzberg, M.; Zhao, X.; Rockway, T. Structure-Directed Discovery of Potent Non-peptidic Inhibitors of Human Urokinase that Access a Novel Binding Subsite. Structure. 2000, 8, 553-563.
113. Klinghofer, V.; Stewart, K.; McGonigal, T.; Smith, R.; Sarthy, A; Nienaber, V.; Butler, C.; Dorwin, S.; Richardson, P.; Weitzberg, M.; Wendt, M.; Rockway, T.; Zhao, X.; Hulkower, K. I.; Giranda, V. L. Species Specificity of Amidine-Based Urokinase Inhibitors. Biochemistry. 2001, 40, 9125-9131.
114. Kaplan, K. L.; Francis, C. W. Direct Thrombin Inhibitors. Semin. Hematol. 2002, 39, 187-196.
115. Zhu, B-Y.; Scarborough, R. M. Factor Xa Inhibitors: Recent Advances in Anticoagulant Agents. Ann. Rep. Med. Chem. 2000, 35, 83-102.
116. Burgess, L. E.; Newhouse, B. J.; Ibrahim, P.; Rizzi, J.; Kashem, M. A.; Hartman, A.; Brandhuber, B. J.; Wright, C. D.; Thomson, D. S.; Vigers, G. P. A.; Koch, K. Potent Selective Nonpeptidic Inhibitors of Human Lung Tryptase. Proc. Natl. Acad. Sci. USA. 1999, 96, 8348-8352.
117. Yawalkar, N.; Schmid, S.; Braathen, L. R.; Pichler, W. J. Perforin and Granzyme B May Contribute to Skin Inflammation in Atopic Dermatitis and Psoriasis. Brit. J. Dermatol. 2001, 144, 1133-1139.
118. Trapani, J. A. Granzymes: a Family of Lymphocyte Granule Serine Proteases. Genome Biology. 2001, 2, 3014.1-3014.7.
119. Concha, N. O.; Abdel-Meguid, S. S. Controlling Apoptosis by Inhibition of Caspases. Curr. Med. Chem. 2002, 9, 713-726.
120. Oberholzer, C.; Oberholzwer, A.; Clare-Salzler, M.; Moldawer, L. L. Apoptosis in Sepsis: A New Target for Therapeutic Exploration. FASEB J. 2001, 15, 879-892.
121. Guttenplan, N.; Lee, C.; Frishman, W. H. Inhibition of Myocardial Apoptosis as a Therapeutic Target in Cardiovascular Disease Prevention. Heart Dis. 2001, 3, 313-318.
122. Olson, R. E.; Thomson, L. A. Secretase Inhibitors as Therapeutics for Alzheimer's Disease. Ann. Rep. Med. Chem. 2000, 35, 31-40.
123. Inhibition of Matrix Metalloproteinases; Greenwald, R. A.; Zucker, S.; Golub, L. M.; Eds.; New York Academy of Sciences: 1999; Vol. 878.
124. Supuran, C. T.; Scozzafava, A.; Clare, B. W. Bacteria Protease Inhibitors. Med. Res. Rev. 2002, 22, 329-372.
125. Woster, P. M. New Therapies for Parasitic Infection. Ann. Rep. Med. Chem. 2001, 36, 99-108.
126. Thomson, L. A.; Tebben, A. J. Pharmacokinetics and Design of Aspartyl Protease Inhibitors. Ann. Rep. Med. Chem. 2001, 36, 247-256.
127. Wang, Q. M. Protease Inhibitors as Potential Antiviral Agents for the Treatment of Picornaviral Infections. Prog. Drug Res. 2001, 229-253.
128. Dragovich, P. S.; Prins, T. J.; Zhou, R.; Brown, E. L.; Maldonado, F. C.; Fuhrman, S. A.; Zalman, L. S.; Tuntland, T.; Lee, C. A.; Patick, A. K.; Matthews, D. A.; Hendrickson, T. F.; Kosa, M. B.; Liu, B.; Batugo, M. R.; Gleeson, J. P.; Sakata, S. K.; Chen. An, M. C.; Meador, J. W.; Ferre, R. A.; Worland, S. T. Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Inhibitors. Structure-Activity Relationship Studies of Orally Bioavailable, 2-Pyridone-Containing Peptidomimetics. J. Med. Chem. 2002, 45, 1607-1623 and references cited therein.
129. Steinkuhler, C.; Koch, U.; Narjes, F.; Matassa, V. G. Hepatitis C Virus Serine Protease Inhibitors: Current Progress and Future Changes. Curr. Med. Chem. 2001, 8, 919-932.
130. Lall, S. L.; Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. Serine and Threonine β-Lactones: A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors. J. Org. Chem. 2002, 67, 1536-1547 and references cited therein.
131. Holwerda, B. C. Herpesvirus Proteases: Targets for Novel Antiviral Drugs. Antiviral Res. 1997, 35, 1-21.
132. Qiu, X.; Janson, C. A.; Culp, J. S.; Richardson, S. B.; Debouck, C.; Smith, W. W.; Abdel-Meguid, S. S. Crystal Structure of Varicella-Zoster Virus Protease. Proc. Natl. Acad. Sci. USA. 1997, 94, 2874-2879.
133. Krishna Murthy, H. M.; Clum, S.; Padmanabhan, R. Dengue Virus NS3 Serine Protease. J. Biol. Chem. 1999, 274, 5573-5580.
134. Curtis, M. A.; Aduse-Opoku, J.; Rangarajan, M. Cysteine Proteases of Porphyromonas Gingivalis. Crit. Rev. Biol. Med. 2001, 12, 192-216.
135. Eichinger, A.; Beisel, H-G.; Jacob, U.; Huber, R.; Medrano, F-J.; Banbula, A.; Potempa, J.; Travis, J.; Bode, W. Crystal Structure of Gingipain R: An Arg-Specific Bacteria Cysteine Proteinase with a Caspase-like Fold. The EMBO J. 1999, 18, 5453-5462.
136. Engel, L. S.; Hill, J. M.; Caballero, A. R.; Green, L. C.; O'Callaghan, R. J. Protease IV, a Unique Extracellular Protease and Virulence Factor from Pseudonomas Aeruginosa. J. Biol. Chem. 1998, 273, 16792-16797.
137. Powers, R. A.; Morandi, F.; Shoichet, B. K. Structure-Based Discovery of a Novel, Non-Covalent Inhibitor of AmpC β-Lactamase. Structure. 2002, 10, 1013-1023.
138. Hernandez, A. A.; Roush, W. R. Recent Advances in the Synthesis, Design and Selection of Cysteine Protease Inhibitors. Curr. Opin. Chem. Biol. 2002, 6, 459-465.
139. Huang, L.; Lee, A.; Ellman, J. A. Identification of Potent and Selective Mechanism-Based Inhibitors of the Cysteine Protease Cruzain Using Solid-Parallel Synthesis. J. Med. Chem. 2002, 45, 676-684 and references cited therein.
140. Schechter, I.; Berger, A. On the Size of the Active Site in Proteases. Biochem. Biophys. Res. Comm. 1967, 255, 3931-3934.