Protease inhibitors: Current status and future prospects

Journal of Medicinal Chemistry

Volumn 43, Issue 3, 2000, Pages 305-341

  Leung, Donmienne ^a   Abbenante, Giovanni ^a   Fairlie, David P ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

[N [4 [(1 ACETIMIDOYL 4 PIPERIDYL)OXY]PHENYL] N [(7 AMIDINO 2 NAPHTHYL)METHYL]SULFAMOYL]ACETIC ACID; AMPRENAVIR; ARGATROBAN; BLOOD CLOTTING FACTOR 10; CALPAIN; CAMOSTAT MESILATE; CANDOXATRIL; CASPASE; CATHEPSIN B; CATHEPSIN L; CYSTEINE PROTEINASE INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EFEGATRAN; ELASTASE; INDINAVIR; LOPINAVIR; MARIMASTAT; METALLOPROTEINASE INHIBITOR; N (1 CARBOXY 3 PHENYLPROPYL)PHENYLALANYLISOSERINE; N (1 HYDROXY 2 NAPHTHOYL)ARGINYLPROLINAMIDE; N [1 (1,3 BENZODIOXOL 5 YL)BUTYL] 3,3 DIETHYL 2 [4 [(4 METHYL 1 PIPERAZINYL)CARBONYL]PHENOXY] 4 OXO 1 AZETIDINECARBOXAMIDE; PLASMEPSIN I; PROTEINASE INHIBITOR; RENIN; RITONAVIR; SEPINOSTAT; THROMBIN; TRYPTASE; TUMOR NECROSIS FACTOR; UNINDEXED DRUG;

DRUG STRUCTURE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PROTEINASE INHIBITION; REVIEW; VIRUS REPLICATION;

ANIMALS; ASPARTIC ENDOPEPTIDASES; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; HUMANS; METALLOENDOPEPTIDASES; MODELS, MOLECULAR; PROTEASE INHIBITORS; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS;

EID: 0034628448     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990412m     Document Type: Review

References (354)

1. Babine, R. E.; Bender, S. L. Molecular recognition of protein-ligand complexes: Applications to drug design. Chem. Rev. 1997, 97, 1359-1472.
2. Ripka, A. S.; Rich, D. H. Peptidomimetic design. Curr. Opin. Chem. Biol. 1998, 2, 441-52.
3. Craik, M. S.; Debouck, C. Proteases as Therapeutic Targets. In Perspectives in Drug Discovery and Design; McKerrow, J. H., James, M. N. G., Eds.; ESCOM: Leiden, 1995; Vol. 2, pp 1-125.
4. Shaw, E. Cysteinyl proteinases and their selective inactivation. Adv. Enzymol. Relat. Areas Mol. Biol. 1990, 63, 271-347.
5. Seife, C. Blunting nature's Swiss army knife [news]. Science 1997, 277, 1602-3.
6. Beckett, R. P.; Davidson, A. H.; Drummond, A. H.; Whittaker, M. Recent advances in matrix metalloproteinase inhibitor research. Drug Discov. Today 1996, 1, 16-26.
7. Johnson, L. L.; Dyer, R.; Hupe, D. J. Matrix metalloproteinases. Curr. Opin. Chem. Biol. 1998, 2, 466-71.
8. Yan, S.; Sameni, M.; Sloane, B. F. Cathepsin B and human tumor progression. Biol. Chem. 1998, 379, 113-23.
9. Becker, M. M.; Harrop, S. A.; Dalton, J. P.; Kalinna, B. H.; McManus, D. P.; Brindley, P. J. Cloning and characterization of the Schistosoma japonicum aspartic proteinase involved in hemoglobin degradation. J. Biol. Chem. 1995, 270, 24496-501.
10. Brindley, P. J.; Kalinna, B. H.; Dalton, J. P.; Day, S. R.; Wong, J. W.; Smythe, M. L.; McManus, D. P. Proteolytic degradation of host hemoglobin by schistosomes. Mol. Biochem. Parasitol. 1997, 89, 1-9.
11. Silva, A. M.; Lee, A. Y.; Gulnik, S. V.; Maier, P.; Collins, J.; Bhat, T. N.; Collins, P. J.; Cachau, R. E.; Luker, K. E.; Gluzman, I. Y.; Francis, S. E.; Oksman, A.; Goldberg, D. E.; Erickson, J. W. Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 10034-9.
12. Li, Z.; Chen, X.; Davidson, E.; Zwang, O.; Mendis, C.; Ring, C. S.; Roush, W. R.; Fegley, G.; Li, R.; Rosenthal, P. J.; et al. Anti-malarial drug development using models of enzyme structure. Chem. Biol. 1994, 1, 31-7.
13. Abad-Zapatero, C.; Goldman, R.; Muchmore, S. W.; Hutchins, C.; Stewart, K.; Navaza, J.; Payne, C. D.; Ray, T. L. Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents. Protein Sci. 1996, 5, 640-52.
14. Abad-Zapatero, C.; Goldman, R.; Muchmore, S. W.; Hutchins, C.; Oie, T.; Stewart, K.; Cutfield, S. M.; Cutfield, J. F.; Foundling, S. I.; Ray, T. L. Structure of secreted aspartic proteinases from Candida - Implications for the design of antifungal agents. Adv. Exp. Med. Biol. 1998, 436, 297-313.
15. Wlodawer, A.; Erickson, J. W. Structure-based inhibitors of HIV-1 protease. Annu. Rev. Biochem. 1993, 62, 543-85.
16. Darke, P. L.; Huff, J. R. HIV protease as an inhibitor target for the treatment of AIDS. Adv. Pharmacol. (San Diego) 1994, 5, 399-454.
17. West, M. L.; Fairlie, D. P. Targeting HIV-1 protease: a test of drug-design methodologies. Trends Pharmacol. Sci. 1995, 16, 67-75.
18. Kim, J. L.; Morgenstern, K. A.; Lin, C.; Fox, T.; Dwyer, M. D.; Landro, J. A.; Chambers, S. P.; Markland, W.; Lepre, C. A.; O'Malley, E. T.; Harbeson, S. L.; Rice, C. M.; Murcko, M. A.; Caron, P. R.; Thomson, J. A. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide [published erratum appears in Cell 1997, 89, 159]. Cell 1996, 87, 343-55.
19. Love, R. A.; Parge, H. E.; Wickersham, J. A.; Hostomsky, Z.; Habuka, N.; Moomaw, E. W.; Adachi, T.; Hostomska, Z. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 1996, 87, 331-42.
20. Gibson, W.; Hall, M. R. Assemblin, an essential herpesvirus proteinase. Drug Des. Discov. 1997, 15, 39-47.
21. Shieh, H. S.; Kurumbail, R. G.; Stevens, A. M.; Stegeman, R. A.; Sturman, E. J.; Pak, J. Y.; Wittwer, A. J.; Palmier, M. O.; Wiegand, R. C.; Holwerda, B. C.; Stallings, W. C. Three-dimensional structure of human cytomegalovirus protease [published erratum appears in Nature 1996, 384, 288]. Nature 1996, 383, 279-82.
22. Bernstein, P. R.; Edwards, P. D.; Williams, J. C. Inhibitors of human leukocyte elastase. Prog. Med. Chem. 1994, 31, 59-120.
23. Hugli, T. E. Protease inhibitors: novel therapeutic application and development. Trends Biotechnol. 1996, 14, 409-12.
24. Fath, M. A.; Wu, X.; Hileman, R. E.; Linhardt, R. J.; Kashem, M. A.; Nelson, R. M.; Wright, C. D.; Abraham, W. M. Interaction of secretory leukocyte protease inhibitor with heparin inhibits proteases involved in asthma. J. Biol. Chem. 1998, 273, 13563-9.
25. Tanaka, R. D.; Clark, J. M.; Warne, R. L.; Abraham, W. M.; Moore, W. R. Mast cell tryptase: a new target for therapeutic intervention in asthma. Int. Arch. Allergy Immunol. 1995, 107, 408-9.
26. Stubbs, M. T.; Bode, W. A player of many parts: the spotlight falls on thrombin's structure. Thromb. Res. 1993, 69, 1-58.
27. Vassar, R.; Bennett, B. D.; Babu-Kahn, S.; Kahn, S.; Mendiaz, E. A.; et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999, 286, 735-41.
28. Vacca, J. P.; Dorsey, B. D.; Schleif, W. A.; Levin, R. B.; McDaniel, S. L.; Darke, P. L.; Zugay, J.; Quintaro, J. C.; Blahy, O. M.; Roth, E.; et al. L-735,524: an orally bio-available human immunodeficiency virus type 1 protease inhibitor. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 4096-100.
29. Kempf, D. J.; Sham, H. L. HIV protease inhibitors. Curr. Pharm. Des. 1996, 2, 225-46.
30. Molla, A.; Granneman, G. R.; Sun, E.; Kempf, D. J. Recent developments in HIV protease inhibitor therapy. Antiviral Res. 1998, 39, 1-23.
31. March, D. R.; Fairlie, D. P. Designing new antiviral drugs for AIDS: HIV-1 Protease and its inhibitors; R. G. Landes Co.: Austin, TX, 1996.
32. Kim, E. E.; Baker, C. T.; Dwyer, M. D.; Murcko, M. A.; Rao, B. G.; Tung, R. D.; Navia, M. A. Crystal structure of HIV-1 protease in complex with VX-478, a potent and orally bioavailable inhibitor of the enzyme. J. Am. Chem. Soc. 1995, 117, 1181-2.
33. Schlechter, I.; Berger, A. On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 1967, 27, 157-62.
34. Fairlie, D. P.; Tyndall, J. D. A.; Reid, R. C.; Wong, A. K.; Abbenante, G.; Scanlon, M. J.; March, D. R.; Bergman, D. A.; Chai, C. L. L.; Burkett, B. A. Conformational selection of inhibitors and substrates by proteolytic enzymes. Implications for drug design and polypeptide processing. J. Med. Chem. 1999, accepted for publication.
35. Tyndall, J. D. A.; Fairlie, D. P. Conformational Homogeneity in Molecular Recognition by Proteolytic enzymes. J. Mol. Recognit. 1999, 12, 1-8.
36. James, M. N. G.; Sielecki, A. R. Aspartic proteases and their catalytic pathway inhibitors. In Biological macromolecules and assemblies: Active sites of enzymes; Jurnak, F. A., McPherson, A., Eds.; John Wiley & Sons: New York, 1987; Vol. 3, p 413.
37. Martin, J. L.; Begun, J.; Schindeler, A.; Wickramasinghe, W. A.; Alewood, D.; Alewood, P. F.; Bergman, D. A.; Brinkworth, R. I.; Abbenante, G.; March, D. R.; Reid, R. C.; Fairlie, D. P. Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease. Biochemistry 1999, 38, 7978-88.
38. Chatfield, D. C.; Brooks, B. R. HIV-1 Protease cleavage mechanism eluciated with molecular-dynamics simulation. J. Am. Chem. Soc. 1995, 117, 5561-72.
39. PDB: www.rcsb.org/pdb.
40. Patick, A. K.; Potts, K. E. Protease inhibitors as antiviral agents. Clin. Microbiol. Rev. 1998, 11, 614-27.
41. Pakyz, A.; Israel, D. Overview of protease inhibitors. J. Am. Pharm. Assoc. (Washington) 1997, NS37, 543-51.
42. Wacher, V. J.; Silverman, J. A.; Zhang, Y.; Benet, L. Z. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 1998, 87, 1322-30.
43. Kempf, D. J.; Marsh, K. C.; Kumar, G.; Rodrigues, A. D.; Denissen, J. F.; McDonald, E.; Kukulka, M. J.; Hsu, A.; Granneman, G. R.; Baroldi, P. A.; Sun, E.; Pizzuti, D.; Plattner, J. J.; Norbeck, D. W.; Leonard, J. M. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob. Agents Chemother. 1997, 41, 654-60.
44. Lea, A. P.; Faulds, D. Ritonavir. Drugs 1996, 52, 541-6 (discussion 547-8).
45. Lacy, M. K.; Abriola, K. P. Indinavir: a pharmacologic and clinical review of a new HIV protease inhibitor. Conn. Med. 1996, 60, 723-7.
46. Shetty, B. V.; Kosa, M. B.; Khalil, D. A.; Webber, S. Preclinical pharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob. Agents Chemother. 1996, 40, 110-4.
47. Adkins, J. C.; Faulds, D. Amprenavir. Drugs 1998, 55, 837-42 (discussion 843-4).
48. Sham, H. L.; Kempf, D. J.; Molla, A.; Marsh, K. C.; Kumar, G. N.; Chen, C. M.; Kati, W.; Stewart, K.; Lal, R.; Hsu, A.; Betebenner, D.; Korneyeva, M.; Vasavanonda, S.; McDonald, E.; Saldivar, A.; Wideburg, N.; Chen, X.; Niu, P.; Park, C.; Jayanti, V.; Grabowski, B.; Granneman, G. R.; Sun, E.; Japour, A. J.; Norbeck, D. W.; et al. ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob. Agents Chemother. 1998, 42, 3218-24.
49. Bold, G.; Fassler, A.; Capraro, H. G.; Cozens, R.; Klimkait, T.; Lazdins, J.; Mestan, J.; Poncioni, B.; Rosel, J.; Stover, D.; Tintelnot-Blomley, M.; Acemoglu, F.; Beck, W.; Boss, E.; Eschbach, M.; Hurlimann, T.; Masso, E.; Roussel, S.; Ucci-Stoll, K.; Wyss, D.; Lang, M. New aza-dipeptide analogues as potent and orally absorbed HIV-1 protease inhibitors: candidates for clinical development. J. Med. Chem. 1998, 41, 3387-401.
50. Lamarre, D.; Croteau, G.; Wardrop, E.; Bourgon, L.; Thibeault, D.; Clouette, C.; Vaillancourt, M.; Cohen, E.; Pargellis, C.; Yoakim, C.; Anderson, P. C. Antiviral properties of palinavir, a potent inhibitor of the human immunodeficiency virus type 1 protease. Antimicrob. Agents Chemother. 1997, 41, 965-71.
51. Kleinert, H. D.; Stein, H. H.; Boyd, S.; Fung, A. K.; Baker, W. R.; Verburg, K. M.; Polakowski, J. S.; Kovar, P.; Barlow, J.; Cohen, J.; et al. Discovery of a well-absorbed, efficacious renin inhibitor, A-74273. Hypertension 1992, 20, 768-75.
52. Menard, J.; Boger, R. S.; Moyse, D. M.; Guyene, T. T.; Glassman, H. N.; Kleinert, H. D. Dose-dependent effects of the renin inhibitor zankiren HCl after a single oral dose in mildly sodium-depleted normotensive subjects. Circulation 1995, 91, 330-8.
53. Sunman, W.; Sever, P. S. Nonangiotensin effects of angiotensin-converting enzyme inhibitors [editorial]. Clin. Sci. (Colch) 1993, 85, 661-70.
54. Rosenberg, S. H. Renin Inhibitors. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier Science: New York, 1995; Vol. 32, pp 37-115.
55. Kleinert, H. D. Renin inhibition. Cardiovasc. Drugs Ther. 1995, 9, 645-55.
56. de Gasparo, M.; Cumin, F.; Nussberger, J.; Guyenne, T. T.; Wood, J. M.; Menard, J. Pharmacological investigations of a new renin inhibitor in normal sodium-unrestricted volunteers. Br. J. Clin. Pharmacol. 1989, 27, 587-96.
57. Kleinbloesem, C. H.; Weber, C.; Fahrner, E.; Dellenbach, M.; Welker, H.; Schroter, V.; Belz, G. G. Hemodynamics, biochemical effects, and pharmacokinetics of the renin inhibitor remikiren in healthy human subjects. Clin. Pharmacol. Ther. 1993, 53, 585-92.
58. Hoover, D. J.; Lefker, B. A.; Rosati, R. L.; Wester, R. T.; Kleinman, E. F.; Bindra, J. S.; Holt, W. F.; Murphy, W. R.; Mangiapane, M. L.; Hockel, G. M.; et al. Discovery of inhibitors of human renin with high oral bioavailability. Adv. Exp. Med. Biol. 1995, 362, 167-80.
59. Simoneau, B.; Lavallee, P.; Anderson, P. C.; Bailey, M.; Bantle, G.; Berthiaume, S.; Chabot, C.; Fazal, G.; Halmos, T.; Ogilvie, W. W.; Poupart, M. A.; Thavonekham, B.; Xin, Z.; Thibeault, D.; Bolger, G.; Panzenbeck, M.; Winquist, R.; Jung, G. L. Discovery of nonpeptidic P2-P3 butanediamide renin inhibitors with high oral efficacy. Bioorg. Med. Chem. 1999, 7, 489-508.
60. Buhlmayer, P.; Caselli, A.; Fuhrer, W.; Goschke, R.; Rasetti, V.; Rueger, H.; Stanton, J. L.; Criscione, L.; Wood, J. M. Synthesis and biological activity of some transition-state inhibitors of human renin. J. Med. Chem. 1988, 31, 1839-46.
61. Plummer, M. S.; Shahripour, A.; Kaltenbronn, J. S.; Lunney, E. A.; Steinbaugh, B. A.; Hamby, J. M.; Hamilton, H. W.; Sawyer, T. K.; Humblet, C.; Doherty, A. M.; et al. Design and synthesis of renin inhibitors: incorporation of transition-state isostere side chains that span from the S1 to the S3 binding pockets and examination of PS-modified renin inhibitors. J. Med. Chem. 1995, 38, 2893-905.
62. Goschke, R.; Cohen, N. C.; Wood, J. M.; Maibaum, J. Novel 2,7-dialkyl substituted 5(S)-amino-4(S)hydroxy-8-phenyl-octanecarboxamides as in vitro potent peptidomimetic inhibitors of human renin. Bioorg. Med. Chem. Lett. 1997, 7, 2735-40.
63. Guller, R.; Binggeli, A.; Breu, V.; Bur, D.; Fischli, W.; Hirth, G.; Jenny, C.; Kansy, M.; Montavon, F.; Muller, M.; Oefner, C.; Stadler, H.; Vieira, E.; Wilhelm, M.; Wostl, W.; Marki, H. P. Piperidine-renin inhibitors compounds with improved physicochemical properties. Bioorg. Med. Chem. Lett. 1999, 9, 1403-8.
64. Vieira, E.; Binggeli, A.; Breu, V.; Bur, D.; Fischli, W.; Guller, R.; Hirth, G.; Marki, H. P.; Muller, M.; Oefner, C.; Scalone, M.; Stadler, H.; Wilhelm, M.; Wostl, W. Substituted piperidines -highly potent renin inhibitors due to induced fit adaptation of the active site. Bioorg. Med. Chem. Lett. 1999, 9, 1397-402.
65. Francis, S. E.; Sullivan, D. J., Jr.; Goldberg, D. E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol. 1997, 51, 97-123.
66. Francis, S. E.; Gluzman, I. Y.; Oksman, A.; Knickerbocker, A.; Mueller, R.; Bryant, M. L.; Sherman, D. R.; Russell, D. G.; Goldberg, D. E. Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase. EMBO J. 1994, 13, 306-17.
67. Carroll, C. D.; Patel, H.; Johnson, T. O.; Guo, T.; Orlowski, M.; He, Z. M.; Cavallaro, C. L.; Guo, J.; Oksman, A.; Gluzman, I. Y.; Connelly, J.; Chelsky, D.; Goldberg, D. E.; Dolle, R. E. Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library. Bioorg. Med. Chem. Lett. 1998, 8, 2315-20.
68. Haque, T. S.; Skillman, A. G.; Lee, C. E.; Habashita, H.; Gluzman, I. Y.; Ewing, T. J.; Goldberg, D. E.; Kuntz, I. D.; Ellman, J. A. Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II. J. Med. Chem. 1999, 42, 1428-40.
69. Semenov, A.; Olson, J. E.; Rosenthal, P. J. Antimalarial synergy of cysteine and aspartic protease inhibitors. Antimicrob. Agents Chemother. 1998, 42, 2254-8.
70. Rochefort, H.; Liaudet-Coopman, E. Cathepsin D in cancer metastasis: a protease and a ligand. APMIS 1999, 107, 86-95.
71. Papassotiropoulos, A.; Bagli, M.; Feder, O.; Jessen, F.; Maier, W.; Rao, M. L.; Ludwig, M.; Schwab, S. G.; Heun, R. Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease. Neurosci. Lett. 1999, 262, 171-4.
72. Wolfe, M. S.; Xia, W.; Moore, C. L.; Leatherwood, D. D.; Ostaszewski, B.; Rahmati, T.; Donkor, I. O.; Selkoe, D. J. Peptidomimetic probes and molecular modeling suggest that Alzheimer's gamma-secretase is an intramembrane-cleaving aspartyl protease. Biochemistry 1999, 38, 4720-7.
73. Baldwin, E. T.; Bhat, T. N.; Gulnik, S.; Hosur, M. V.; Sowder, R. C. d.; Cachau, R. E.; Collins, J.; Silva, A. M.; Erickson, J. W. Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6796-800.
74. Majer, P.; Collins, J. R.; Gulnik, S. V.; Erikson, J. W. Substrate-based subsite specificity mapping of human cathepsin D using statine-based inhibitors. Protein Sci. 1997, 6, 1458-66.
75. Whitesitt, C. A.; Simon, R. L.; Reel, J. K.; Sigmund, S. K.; Phillips, M. L.; Shadle, J. K.; Heinz, L. J.; Koppel, G. A.; Hunden, D. C.; Lifer, S. L.; Berry, D.; Ray, J.; Little, S. P.; Liu, X. D.; Marshall, W. S.; Panetta, J. A. Synthesis and structure - activity relationships of benzophenones as inhibitors of cathepsin D. Bioorg. Med. Chem. Lett. 1996, 6, 2157-62.
76. Kick, E. K.; Roe, D. C.; Skillman, A. G.; Liu, G.; Ewing, T. J.; Sun, Y.; Kuntz, I. D.; Ellman, J. A. Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D. Chem. Biol. 1997, 4, 297-307.
77. Lee, C. E.; Kick, E. K.; Ellman, J. A. General solid-phase synthesis approach to prepare mechanism-based aspartyl protease inhibitor libraries. Identification of potent cathepsin D inhibitors. J. Am. Chem. Soc. 1998, 120, 9735-47.
78. Gruber, A.; Speth, C.; Lukasser-Vogl, E.; Zangerle, R.; Borg-von Zepelin, M.; Dierich, M. P.; Wurzner, R. Human immunodeficiency virus type 1 protease inhibitor attenuates Candida albicans virulence properties in vitro. Immunopharmacology 1999, 41, 227-34.
79. De Bernardis, F.; Arancia, S.; Morelli, L.; Hube, B.; Sanglard, D.; Schafer, W.; Cassone, A. Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis. J. Infect. Dis. 1999, 179, 201-8.
80. Naglik, J. R.; Newport, G.; White, T. C.; Fernandes-Naglik, L. L.; Greenspan, J. S.; Greenspan, D.; Challacombe, S. J.; Agabian, N. In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis. Infect. Immun. 1999, 67, 2482-90.
81. Hube, B.; Sanglard, D.; Odds, F. C.; Hess, D.; Monod, M.; Schafer, W.; Brown, A. J. P.; Gow, N. A. R. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect. Immun. 1997, 65, 3529-38.
82. Sanglard, D.; Hube, B.; Monod, M.; Odds, F. C.; Gow, N. A. A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. Infect. Immun. 1997, 65, 3539-46.
83. Monod, M.; Hube, B.; Hess, D.; Sanglard, D. Differential regulation of SAP8 and SAP9, which encode two new members of the secreted aspartic proteinase family in Candida albicans. Microbiology 1998, 144, 2731-7.
84. Cutfield, S. M.; Dodson, E. J.; Anderson, B. F.; Moody, P. C.; Marshall, C. J.; Sullivan, P. A.; Cutfield, J. F. The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors. Structure 1995, 3, 1261-71.
85. Symersky, J.; Monod, M.; Foundling, S. I. High-resolution structure of the extracellular aspartic proteinase from Candida tropicalis yeast. Biochemistry 1997, 36, 12700-10.
86. Rich, D. H. Pepstatin-derived inhibitors of aspartic proteinases. A close look at an apparent transition-state analogue inhibitor. J. Med. Chem. 1985, 28, 263-73.
87. Powers, J. C.; Harper, J. W. Inhibitors of serine proteases. Proteinase Inhib. 1986, 55-152.
88. Rawlings, N. D.; Barrett, A. J. Families of serine peptidases. Methods Enzymol. 1994, 244, 19-61.
89. Barrett, A. J.; Rawlings, N. D. Families and clans of serine peptidases. Arch. Biochem. Biophys. 1995, 318, 247-50.
90. Verstraete, M. Modulating platelet function with selective thrombin inhibitors. Haemostasia 1996, 26, 70-7.
91. Sanderson, P. E. J.; NaylorOlsen, A. M. Thrombin inhibitor design. Curr. Med. Chem. 1998, 5, 289-304.
92. Vacca, J. P. Thrombosis and coagulation. Annu. Rep. Med. Chem. 1998, 33, 81-90.
93. Rawson, T. E.; VanGorp, K. A.; Yang, J.; Kogan, T. P. Separation of 21-(R)-and 21-(S)-argatroban: solubility and activity of the individual diastereoisomers [letter]. J. Pharm. Sci. 1993, 82, 672-3.
94. Schwartz, R. P.; Becker, J.-C. P.; Brooks, R. L.; Hursting, M. J.; Joffrion, J. L.; Knappenberger, G. D.; Kogan, T. P.; Kogan, P. W.; McKinney, A. A. The preclinical and clinical pharmacology of Novastan (Argatroban): A small-molecule, direct thrombin inhibitor. Clin. Appl. Thromb. Hemost. 1997, 3, 1-15.
95. Hilpert, K.; Ackermann, J.; Banner, D. W.; Gast, A.; Gubernator, K.; Hadvary, P.; Labler, L.; Muller, K.; Schmid, G.; Tschopp, T. B.; et al. Design and synthesis of potent and highly selective thrombin inhibitors. J. Med. Chem. 1994, 37, 3889-901.
96. Bounameaux, H.; Ehringer, H.; Hulting, J.; Rasche, H.; Rapold, H. J.; Zultak, M. An exploratory trial of two dosages of a novel synthetic thrombin inhibitor (napsagatran, Ro 46-6240) compared with unfractionated heparin for treatment of proximal deep-vein thrombosis - - results of the European multicenter ADVENT trial. Thromb. Haemost. 1997, 78, 997-1002.
97. Roux, S.; Tschopp, T.; Baumgartner, H. R. Effects of napsagatran (Ro 46-6240), a new synthetic thrombin inhibitor and of heparin in a canine model of coronary artery thrombosis: comparison with an ex vivo annular perfusion chamber model. J. Pharmacol. Exp. Ther. 1996, 277, 71-8.
98. Teger-Nilsson, A. C.; Bylund, R.; Gustafsson, D.; Gyzander, E.; Eriksson, U. In vitro effects of inogatran, a selective low molecular weight thrombin inhibitor. Thromb. Res. 1997, 85, 133-45.
99. Preville, P.; He, J. X.; Tarazi, M.; Siddiqui, M. A.; Cody, W. L.; Doherty, A. M. An efficient preparation of the potent and selective pseudopeptide thrombin inhibitor, inogatran. Bioorg. Med. Chem. Lett. 1997, 7, 1563-6.
100. Eriksson, U. G.; Renberg, L.; Bredberg, U.; Teger-Nilsson, A. C.; Regardh, C. G. Animal pharmacokinetics of inogatran, a low-molecular-weight thrombin inhibitor with potential use as an antithrombotic drug. Biopharm. Drug Dispos. 1998, 19, 55-64.
101. Jackson, C. V.; Satterwhite, J.; Roberts, E. Preclinical and clinical pharmacology of efegatran (LY294468): A novel antithrombin for the treatment of acute coronary syndromes. Clin. Appl. Thromb. Hemost. 1996, 2, 258-67.
102. Rebello, S. S.; Miller, B. V.; Basler, G. C.; Lucchesi, B. R. CVS-1123, a direct thrombin inhibitor, prevents occlusive arterial and venous thrombosis in a canine model of vascular injury. J. Cardiovasc. Pharmacol. 1997, 29, 240-9.
103. Cousins, G. R.; Friedrichs, G. S.; Sudo, Y.; Rebello, S. S.; Rote, W. E.; Vlasuk, G. P.; Nolan, T. G.; Mendoza, C.; Lucchesi, B. R. Orally effective CVS-1123 prevents coronary artery thrombosis in the conscious dog. Circulation 1996, 94, 1705-12.
104. Kettner, C.; Mersinger, L.; Knabb, R. The selective inhibition of thrombin by peptides of boroarginine. J. Biol. Chem. 1990, 265, 18289-97.
105. Knabb, R. M.; Kettner, C. A.; Timmermans, P. B.; Reilly, T. M. In vivo characterization of a new synthetic thrombin inhibitor. Thromb. Haemost. 1992, 67, 56-9.
106. Quan, M. L.; Wityak, J.; Dominguez, C.; Duncia, J. V.; Kettner, C. A.; Ellis, C. D.; Liauw, A. Y.; Park, J. M.; Santella, J. B.; Knabb, R. M.; Thoolen, M. J.; Weber, P. C.; Wexler, R. R. Biaryl substituted alkylboronate esters as thrombin inhibitors. Bioorg. Med. Chem. Lett. 1997, 7, 1595-600.
107. Allen, M.; Abel, S. M.; Barber, C. G.; Cussans, N. J.; Danilewicz, J. C.; Elliss, D.; Hawkeswood, E.; Herron, M.; Holland, S.; Fox, D. N. A.; James, K.; Kobylecki, R. J.; Overington, J. P.; Pandit, J.; Parmer, H.; Powling, M.; Rance, D. J.; Taylor, W.; Shepperson, N. B. 215th ACS National Meeting, Dallas, TX, Mar 29-Apr 2, 1998; Abstr. MEDI 200.
108. Tucker, T. J.; Lumma, W. C.; Lewis, S. D.; Gardell, S. J.; Lucas, B. J.; Baskin, E. P.; Woltmann, R.; Lynch, J. J.; Lyle, E. A.; Appleby, S. D.; Chen, I. W.; Dancheck, K. B.; Vacca, J. P. Potent noncovalent thrombin inhibitors that utilize the unique amino acid D-dicyclohexylalanine in the P3 position. Implications on oral bioavailability and antithrombotic efficacy. J. Med. Chem. 1997, 40, 1565-9.
109. Brady, S. F.; Stauffer, K. J.; Lumma, W. C.; Smith, G. M.; Ramjit, H. G.; Lewis, S. D.; Lucas, B. J.; Gardell, S. J.; Lyle, E. A.; Appleby, S. D.; Cook, J. J.; Holahan, M. A.; Stranieri, M. T.; Lynch, J. J.; Lin, J. H.; Chen, I. W.; Vastag, K.; NaylorOlsen, A. M.; Vacca, J. P. Discovery and development of the novel potent orally active thrombin inhibitor N-(9-hydroxy-9-fluorenecarboxy)prolyl trans-4-aminocyclohexylmethyl amide (L-372,460): Coapplication of structure-based design and rapid multiple analogue synthesis on solid support. J. Med. Chem. 1998, 41, 401-6.
110. Malley, M. F.; Tabernero, L.; Chang, C. Y.; Ohringer, S. L.; Roberts, D. G.; Das, J.; Sack, J. S. Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090. Protein Sci. 1996, 5, 221-8.
111. Chirgadze, N. Y.; Sall, D. J.; Klimkowski, V. J.; Clawson, D. K.; Briggs, S. L.; Hermann, R.; Smith, G. F.; Gifford-Moore, D. S.; Wery, J. P. The crystal structure of human alpha-thrombin complexed with LY178550, a nonpeptidyl, active site-directed inhibitor. Protein Sci. 1997, 6, 1412-7.
112. Gustafsson, D.; Antonsson, T.; Bylund, R.; Eriksson, U.; Gyzander, E.; Nilsson, I.; Elg, M.; Mattsson, C.; Deinum, J.; Pehrsson, S.; Karlsson, O.; Nilsson, A.; Sorensen, H. Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thromb. Haemost. 1998, 79, 110-8.
113. Mehta, J. L.; Chen, L. Y.; Nichols, W. W.; Mattsson, C.; Gustafsson, D.; Saldeen, T. G. P. Melagatran, an oral activesite inhibitor of thrombin, prevents or delays formation of electrically induced occlusive thrombus in the canine coronary artery. J. Cardiovasc. Pharmacol. 1998, 31, 345-51.
114. Lila, C.; Gloanec, P.; Cadet, L.; Herve, Y.; Fournier, J.; Leborgne, F.; Verbeuren, T. J.; DeNanteuil, G. Large scale preparation of protected 4-aminomethylbenzamidine. Application to the synthesis of the thrombin inhibitor, melagatran. Synth. Commun. 1998, 28, 4419-29.
115. Kaiser, B. Factor Xa versus factor IIa inhibitors. Clin. Appl. Thromb. Hemost. 1997, 3, 16-24.
116. Hara, T.; Yokoyama, A.; Ishihara, H.; Yokoyama, Y.; Nagahara, T.; Iwamoto, M. Dx-9065a, a New Synthetic, Potent Anticoagulant and Selective Inhibitor For Factor-Xa. Thromb. Haemost. 1994, 71, 314-9.
117. Hara, T.; Yokoyama, A.; Tanabe, K.; Ishihara, H.; Iwamoto, M. DX-9065a, an orally active, specific inhibitor of factor Xa, inhibits thrombosis without affecting bleeding time in rats. Thromb. Haemost. 1995, 74, 635-9.
118. Herbert, J. M.; Bernat, A.; Dol, F.; Herault, J. P.; Crepon, B.; Lormeau, J. C. DX 9065A, a novel, synthetic, selective and orally active inhibitor of factor xa: In vitro and in vivo studies. J. Pharm. Exp. Ther. 1996, 276, 1030-8.
119. Katakura, S.; Nagahara, T.; Hara, T.; Iwamoto, M. A novel factor Xa inhibitor: structure-activity relationships and selectivity between factor Xa and thrombin. Biochem. Biophys. Res. Commun. 1993, 197, 965-72.
120. Katakura, S.; Nagahara, T.; Hara, T.; Kunitada, S.; Iwamoto, M. Molecular model of an interaction between factor Xa and DX-9065a, a novel factor Xa inhibitor: Contribution of the acetimidoylpyrrolidine moiety of the inhibitor to potency and selectivity for serine proteases. Eur. J. Med. Chem. 1995, 30, 387-94.
121. Brandstetter, H.; Kuhne, A.; Bode, W.; Huber, R.; vonderSaal, W.; Wirthensohn, K.; Engh, R. A. X-ray structure of active site-inhibited clotting factor Xa - Implications for drug design and substrate recognition. J. Biol. Chem. 1996, 271, 29988-92.
122. Morishima, Y.; Tanabe, K.; Terada, Y.; Hara, T.; Kunitada, S. Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective factor Xa inhibitor: Comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants. Thromb. Haemost. 1997, 78, 1366-71.
123. Taniuchi, Y.; Sakai, Y.; Hisamichi, N.; Kayama, M.; Mano, Y.; Sato, K.; Hirayama, F.; Koshio, H.; Matsumoto, Y.; Kawasaki, T. Biochemical and pharmacological characterization of YM-60828, a newly synthesized and orally active inhibitor of human factor Xa. Thromb. Haemost. 1998, 79, 543-8.
124. Kawasaki, T.; Sato, K.; Sakai, Y.; Hirayama, F.; Koshio, H.; Taniuchi, Y.; Matsumoto, Y. Comparative studies of an orally active factor Xa inhibitor, YM-60828, with other antithrombotic agents in a rot model of arterial thrombosis. Thromb. Haemost. 1998, 79, 410-6.
125. Sato, K.; Kawasaki, T.; Hisamichi, N.; Taniuchi, Y.; Hirayama, F.; Koshio, H.; Matsumoto, Y. Antithrombotic effects of YM-60828, a newly synthesized factor Xa inhibitor, in rat thrombosis models and its effects on bleeding time. Br. J. Pharmacol. 1998, 123, 92-6.
126. Kamata, K.; Kawamoto, H.; Honma, T.; Iwama, T.; Kim, S. H. Structural basis for chemical inhibition of human blood coagulation factor Xa. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 6630-5.
127. Klein, S. I.; Czekaj, M.; Gardner, C. J.; Guertin, K. R.; Cheney, D. L.; Spada, A. P.; Bolton, S. A.; Brown, K.; Colussi, D.; Heran, C. L.; Morgan, S. R.; Leadley, R. J.; Dunwiddie, C. T.; Perrone, M. H.; Chu, V. Identification and initial structure-activity relationships of a novel class of nonpeptide inhibitors of blood coagulation factor Xa. J. Med. Chem. 1998, 41, 437-50.
128. Kucznierz, R.; Grams, F.; Leinert, H.; Marzenell, K.; Engh, R. A.; von der Saal, W. Tetrahydro-isoquinoline-based factor Xa inhibitors. J. Med. Chem. 1998, 41, 4983-94.
129. Edwards, P. D.; Bernstein, P. R. Synthetic inhibitors of elastase. Med. Res. Rev. 1994, 14, 127-94.
130. Williams, J. C.; Stein, R. L.; Giles, R. E.; Krell, R. D. Biochemistry and pharmacology of ICI 200,880, a synthetic peptide inhibitor of human neutrophil elastase. Ann. N. Y. Acad. Sci. 1991, 624, 230-43.
131. Sommerhoff, C. P.; Krell, R. D.; Williams, J. L.; Gomes, B. C.; Strimpler, A. M.; Nadel, J. A. Inhibition of human neutrophil elastase by ICI 200,355. Eur. J. Pharmacol. 1991, 193, 153-8.
132. O'Riordan, T. G.; Otero, R.; Mao, Y.; Lauredo, I.; Abraham, W. M. Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways. Am. J. Respir. Crit. Care Med. 1997, 155, 1522-8.
133. Williams, J. C.; Falcone, R. C.; Knee, C.; Stein, R. L.; Strimpler, A. M.; Reaves, B.; Giles, R. E.; Krell, R. D. Biologic characterization of ICI 200,880 and ICI 200,355, novel inhibitors of human neutrophil elastase. Am. Rev. Respir. Dis. 1991, 144, 875-83.
134. Anderson, G. P.; Shinagawa, K. Neutrophil elastase inhibitors as treatments for emphysema and chronic bronchitis. Curr. Opin. Anti-inflam. Immun. Invest. Drugs 1999, 1, 29-38.
135. Luisetti, M.; Sturani, C.; Sella, D.; Madonini, E.; Galavotti, V.; Bruno, G.; Peona, V.; Kucich, U.; Dagnino, G.; Rosenbloom, J.; Starcher, B.; Grassi, C. MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial. Eur. Respir. J. 1996, 9, 1482-6.
136. Luisetti, M.; Piccioni, P. D.; Donnini, M.; Peona, V.; Pozzi, E.; Grassi, C. Studies of MR 889, a new synthetic proteinase inhibitor. Biochem. Biophys. Res. Commun. 1989, 165, 568-73.
137. Baici, A.; Pelloso, R.; Horler, D. The kinetic mechanism of inhibition of human leukocyte elastase by MR889, a new cyclic thiolic compound. Biochem. Pharmacol. 1990, 39, 919-24.
138. Kawabata, K.; Suzuki, M.; Sugitani, M.; Imaki, K.; Toda, M.; Miyamoto, T. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem. Biophys. Res. Commun. 1991, 177, 814-20.
139. Iwamura, H.; Moore, A. R.; Willoughby, D. A. Interaction between neutrophil-derived elastase and reactive oxygen species in cartilage degradation. Biochim. Biophys. Acta 1993, 1156, 295-301.
140. Kakimoto, K.; Matsukawa, A.; Yoshinaga, M.; Nakamura, H. Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis. Cell. Immunol. 1995, 165, 26-32.
141. Inada, M.; Yamashita, J.; Ogawa, M. Neutrophil elastase inhibitor (ONO-5046-Na) inhibits the growth of human lung cancer cell lines transplanted into severe combined immunodeficiency (scid) mice. Res. Commun. Mol. Pathol. Pharmacol. 1997, 97, 229-32.
142. Kobayashi, J.; Kitamura, S. How can we monitor and treat patients with acute exacerbations of idiopathic interstitial pneumonia. Nihon Kyobu Shikkan Gakkai Zasshi 1996, 34, 195-9.
143. Watanabe, F.; Sato, M.; Kato, A.; Murakami, T.; Higashi, Y.; Yata, N. First-pass metabolism of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl]aminoacetic acid), a novel elastase inhibitor, in rats. Biol. Pharm. Bull. 1997, 20, 392-6.
144. Finke, P. E.; Shah, S. K.; Ashe, B. M.; Ball, R. G.; Blacklock, T. J.; Bonney, R. J.; Brause, K. A.; Chandler, G. O.; Cotton, M.; Davies, P.; et al. Inhibition of human leukocyte elastase. 4. Selection of a substituted cephalosporin (L-658,758) as a topical aerosol. J. Med. Chem. 1992, 35, 3731-44.
145. Pacholok, S. G.; Davies, P.; Dorn, C.; Finke, P.; Hanlon, W. A.; Mumford, R. A.; Humes, J. L. Formation of polymorphonuclear leukocyte elastase: alpha 1 proteinase inhibitor complex and A alpha (1-21) fibrinopeptide in human blood stimulated with the calcium ionophore A23187. A model to characterize inhibitors of polymorphonuclear leukocyte elastase. Biochem. Pharmacol. 1995, 49, 1513-20.
146. Thompson, K. R.; Finke, P. E.; Shah, S. K.; Ashe, B. M.; Dahlgren, M. E.; Maycock, A. L.; Doherty, J. B. Inhibition of human leukocyte elastase. 6. Inhibiton by 6-substituted penicillin esters. Bioorg. Med. Chem. Lett. 1993, 3, 2283-8.
147. Thompson, K. R.; Finke, P. E.; Shah, S. K.; Ashe, B. M.; Dahlgren, M. E.; Dellea, P. S.; Fletcher, D. S.; Hand, K. M.; Maycock, A. L.; Doherty, J. B. Inhibition of human leukocyte elastase. 7. Inhibiton by 6-substituted penicillin amides. Bioorg. Med. Chem. Lett. 1993, 3, 2289-94.
148. Finke, P. E.; Dahlgren, M. E.; Weston, H.; Maycock, A. L.; Doherty, J. B. Inhibition of human leukocyte elastase. 5. Inhibiton by 6-alkyl substituted penem benzyl esters. Bioorg. Med. Chem. Lett. 1993, 3, 2277-82.
149. Maillard, J. L.; Favreau, C.; Reboud-Ravaux, M.; Kobaiter, R.; Joyeau, R.; Wakselman, M. Biological evaluation of the inhibition of neutrophil elastase by a synthetic beta-lactam derivative. Eur. J. Cell Biol. 1990, 52, 213-8.
150. Knight, W. B.; Green, B. G.; Chabin, R. M.; Gale, P.; Maycock, A. L.; Weston, H.; Kuo, D. W.; Westler, W. M.; Dorn, C. P.; Finke, P. E.; et al. Specificity, stability, and potency of monocyclic beta-lactam inhibitors of human leucocyte elastase. Biochemistry 1992, 31, 8160-70.
151. Kerrigan, J. E.; Oleksyszyn, J.; Kam, C. M.; Selzler, J.; Powers, J. C. Mechanism-based isocoumarin inhibitors for human leukocyte elastase. Effect of the 7-amino substituent and 3-alkoxy group in 3-alkoxy-7-amino-4-chloroisocoumarins on inhibitory potency. J. Med. Chem. 1995, 38, 544-52.
152. Hlasta, D. J.; Ackerman, J. H.; Court, J. J.; Farrell, R. P.; Johnson, J. A.; Kofron, J. L.; Robinson, D. T.; Talomie, T. G.; Dunlap, R. P.; Franke, C. A. A novel class of cyclic beta-dicarbonyl leaving groups and their use in the design of benzisothiazolone human leukocyte elastase inhibitors. J. Med. Chem. 1995, 38, 4687-92.
153. Hlasta, D. J.; Subramanyam, C.; Bell, M. R.; Carabateas, P. M.; Court, J. J.; Desai, R. C.; Drozd, M. L.; Eickhoff, W. M.; Ferguson, E. W.; Gordon, R. J.; et al. Orally bioavailable benzisothiazolone inhibitors of human leukocyte elastase. J. Med. Chem. 1995, 38, 739-44.
154. Finke, P. E.; Shah, S. K.; Fletcher, D. S.; Ashe, B. M.; Brause, K. A.; Chandler, G. O.; Dellea, P. S.; Hand, K. M.; Maycock, A. L.; Osinga, D. G.; et al. Orally active beta-lactam inhibitors of human leukocyte elastase. 3. Stereospecific synthesis and structure-activity relationships for 3,3-dialkylazetidin-2-ones. J. Med. Chem. 1995, 38, 2449-62.
155. Macdonald, S. J.; Belton, D. J.; Buckley, D. M.; Spooner, J. E.; Anson, M. S.; Harrison, L. A.; Mills, K.; Upton, R. J.; Dowle, M. D.; Smith, R. A.; Molloy, C. R.; Risley, C. Syntheses of trans-5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles and trans-5-oxo-hexahydrofuro[3,2-b]pyrroles (pyrrolidine trans-lactams and trans-lactones): new pharmacophores for elastase inhibition. J. Med. Chem. 1998, 41, 3919-22.
156. Cregge, R. J.; Durham, S. L.; Farr, R. A.; Gallion, S. L.; Hare, C. M.; Hoffman, R. V.; Janusz, M. J.; Kim, H. O.; Koehl, J. R.; Mehdi, S.; Metz, W. A.; Peet, N. P.; Pelton, J. T.; Schreuder, H. A.; Sunder, S.; Tardif, C. Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones. J. Med. Chem. 1998, 41, 2461-80.
157. Angelastro, M. R.; Baugh, L. E.; Bey, P.; Burkhart, J. P.; Chen, T. M.; Durham, S. L.; Hare, C. M.; Huber, E. W.; Janusz, M. J.; Koehl, J. R.; et al. Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones. J. Med. Chem. 1994, 37, 4538-53.
158. Burkhart, J. P.; Koehl, J. R.; Mehdi, S.; Durham, S. L.; Janusz, M. J.; Huber, E. W.; Angelastro, M. R.; Sunder, S.; Metz, W. A.; Shum, P. W.; et al. Inhibition of human neutrophil elastase. 3. An orally active enol acetate prodrug. J. Med. Chem. 1995, 38, 223-33.
159. Veale, C. A.; Bernstein, P. R.; Bohnert, C. M.; Brown, F. J.; Bryant, C.; Damewood, J. R., Jr.; Earley, R.; Feeney, S. W.; Edwards, P. D.; Gomes, B.; Hulsizer, J. M.; Kosmider, B. J.; Krell, R. D.; Moore, G.; Salcedo, T. W.; Shaw, A.; Silberstein, D. S.; Steelman, G. B.; Stein, M.; Strimpler, A.; Thomas, R. M.; Vacek, E. P.; Williams, J. C.; Wolanin, D. J.; Woolson, S. Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase. J. Med. Chem. 1997, 40, 3173-81.
160. Edwards, P. D.; Andisik, D. W.; Bryant, C. A.; Ewing, B.; Gomes, B.; Lewis, J. J.; Rakiewicz, D.; Steelman, G.; Strimpler, A.; Trainor, D. A.; Tuthill, P. A.; Mauger, R. C.; Veale, C. A.; Wildonger, R. A.; Williams, J. C.; Wolanin, D. J.; Zottola, M. Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase. J. Med. Chem. 1997, 40, 1876-85.
161. Bernstein, P. R.; Gomes, B. C.; Kosmider, B. J.; Vacek, E. P.; Williams, J. C. Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone. J. Med. Chem. 1995, 38, 212-5.
162. Veale, C. A.; Damewood, J. R., Jr.; Steelman, G. B.; Bryant, C.; Gomes, B.; Williams, J. Nonpeptidic inhibitors of human leukocyte elastase. 4. Design, synthesis, and in vitro and in vivo activity of a series of beta-carbolinone-containing trifluoromethyl ketones. J. Med. Chem. 1995, 38, 86-97.
163. Veale, C. A.; Bernstein, P. R.; Bryant, C.; Ceccarelli, C.; Damewood, J. R., Jr.; Earley, R.; Feeney, S. W.; Gomes, B.; Kosmider, B. J.; Steelman, G. B.; et al. Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, synthesis, and X-ray crystallography of a series of orally active 5-aminopyrimidin-6-one-containing trifluoromethyl ketones. J. Med. Chem. 1995, 38, 98-108.
164. Brown, F. J.; Andisik, D. W.; Bernstein, P. R.; Bryant, C. B.; Ceccarelli, C.; Damewood, J. R., Jr.; Edwards, P. D.; Earley, R. A.; Feeney, S.; Green, R. C.; et al. Design of orally active, nonpeptidic inhibitors of human leukocyte elastase. J. Med. Chem. 1994, 37, 1259-61.
165. Edwards, P. D.; Andisik, D. W.; Strimpler, A. M.; Gomes, B.; Tuthill, P. A. Nonpeptidic inhibitors of human neutrophil elastase. 7. Design, synthesis, and in vitro activity of a series of pyridopyrimidine trifluoromethyl ketones. J. Med. Chem. 1996, 39, 1112-24.
166. Portevin, B.; Lonchampt, M.; Canet, E.; De Nanteuil, G. Dual inhibition of human leukocyte elastase and lipid peroxidation: in vitro and in vivo activities of azabicyclo[2.2.2]octane and perhydroindole derivatives. J. Med. Chem. 1997, 40, 1906-18.
167. 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, 1729-40.
168. 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, 539-44.
169. Guy, L.; Vidal, J.; Collet, A.; Amour, A.; Reboud-Ravaux, M. Design and synthesis of hydrazinopeptides and their evaluation as human leukocyte elastase inhibitors. J. Med. Chem. 1998, 41, 4833-43.
170. Schwartz, L. B. Tryptase: a mast cell serine protease. Methods Enzymol. 1994, 244, 88-100.
171. Walls, A. F. The roles of neutral proteases in asthma and rhinitis. In Asthma and rhinitis; Busse, W. W., Holgate, S. T., Eds.; Blackwell: Oxford, 1995; pp 801-825.
172. Matsumoto, R.; Sali, A.; Ghildyal, N.; Karplus, M.; Stevens, R. L. Packaging of proteases and proteoglycans in the granules of mast cells and other hematopoietic cells. A cluster of histidines on mouse mast cell protease 7 regulates its binding to heparin serglycin proteoglycans. J. Biol. Chem. 1995, 270, 19524-31.
173. Stubbs, M. T.; Morenweiser, R.; Sturzebecher, J.; Bauer, M.; Bode, W.; Huber, R.; Piechottka, G. P.; Matschiner, G.; Sommerhoff, C. P.; Fritz, H.; Auerswald, E. A. The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition. J. Biol. Chem. 1997, 272, 19931-7.
174. Rice, K. D.; Tanaka, R. D.; Katz, B. A.; Numerof, R. P.; Moore, W. R. Inhibitors of tryptase for the treatment of mast cell-mediated diseases. Curr. Pharm. Des. 1998, 4, 381-96.
175. Katz, B. A.; Clark, J. M.; FinerMoore, J. S.; Jenkins, T. E.; Johnson, C. R.; Ross, M. J.; Luong, C.; Moore, W. R.; Stroud, R. M. Design of potent selective zinc-mediated serine protease inhibitors. Nature 1998, 391, 608-12.
176. Clark, J. M.; Abraham, W. M.; Fishman, C. E.; Forteza, R.; Ahmed, A.; Cortes, A.; Warne, R. L.; Moore, W. R.; Tanaka, R. D. Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep. Am. J. Respir. Crit. Care Med. 1995, 152, 2076-83.
177. Molinari, J. F.; Scuri, M.; Moore, W. R.; Clark, J.; Tanaka, R.; Abraham, W. M. Inhaled tryptase causes bronchoconstriction in sheep via histamine release. Am. J. Respir. Crit. Care Med. 1996, 154, 649-53.
178. Van Noorden, J. F. IBC's 2nd International Conference on Protease Inhibitors: Novel Therapeutic Applications and Development, Washington DC, 24-26 February. Acta Histochem. 1997, 249-55.
179. Combrink, K. D.; Gulgeze, H. B.; Meanwell, N. A.; Pearce, B. C.; Zulan, P.; Bisacchi, G. S.; Roberts, D. G.; Stanley, P.; Seiler, S. M. 1,2-Benzisothiazol-3-one 1,1-dioxide inhibitors of human mast cell tryptase. J. Med. Chem. 1998, 41, 4854-60.
180. Whaley, K. Complement in health and disease; MTP Press Ltd.: Lancaster, 1987.
181. Sim, E. The natural immune system: Humoral factors; Oxford University Press: Oxford, 1993.
182. Ember, J. A.; Hugli, T. E. Complement factors and their receptors. Immunopharmacology 1997, 38, 3-15.
183. Gerard, C.; Gerard, N. P. C5A anaphylatoxin and its seven transmembrane-segment receptor. Annu. Rev. Immunol. 1994, 12, 775-808.
184. Oda, M.; Ino, Y.; Nakamura, K.; Kuramoto, S.; Shimamura, K.; Iwaki, M.; Fujii, S. Pharmacological studies on 6-amidino-2-naphthyl[4-(4,5-dmydro-1H-imidazol-2-yl)amino] benzoate dimethane sulfonate (FUT-187). I: Inhibitory activities on various kinds of enzymes in vitro and anticomplement activity in vivo. Jpn. J. Pharmacol. 1990, 52, 23-34.
185. Nakamura, K.; Johmura, A.; Oda, M.; Ino, Y.; Uchiyama, H.; Ohtani, H.; Miyazaki, H.; Kurumi, M.; Akizawa, Y.; Oka, T. Inhibitory effects of sepimostat mesilate (FUT-187) on the activities of trypsin-like serine proteases in vitro. Yakugaku Zasshi 1995, 115, 201-12.
186. Sepimostat Mesilate. Drugs Future 1997, 22, 502-7.
187. Abe, O.; Yoshino, K.; Kimura, K.; Suzuki, H.; Aoki, T.; Hiki, Y.; Mitomi, T.; Makuuchi, H. Early phase II study of FUT-187 (sepimostat mesilate) on reflux esophagitis - mainly on postgastrectomy reflux esophagitis. Gan To Kagaku Ryoho 1994, 21, 845-52.
188. Shiozaki, H.; Inoue, M.; Tamura, S.; Iwanaga, T.; Imaoka, M.; Furukawa, H.; Hiratsuka, M.; Kikkawa, N.; Kobayashi, K.; Okamura, J.; Takada, N.; Ogawa, Y.; Yamada, T.; Takami, M.; Takada, T.; Okuda, H.; Yano, T.; Satomi, T.; Kawasaki, T.; Oshima, S.; Yamasaki, K.; Imamoto, H.; Noguchi, S.; Fujimoto, N.; Mori, T.; et al. Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant. Gan To Kagaku Ryoho 1996, 23, 1971-9.
189. Makuuchi, H.; Kanno, K.; Mitomi, T. Clinical usefulness of FUT-187 (sepimostat mesilate) on reflux esophagitis and gastritis after gastrectomy. Gan To Kagaku Ryoho 1995, 22, 777-83.
190. Ikari, N.; Sakai, Y.; Hitomi, Y.; Fujii, S. New synthetic inhibitor to the alternative complement pathway. Immunology 1983, 49, 685-91.
191. Inagi, R.; Miyata, T.; Maeda, K.; Sugiyama, S.; Miyama, A.; Nakashima, I. FUT-175 as a potent inhibitor of C5/C3 convertase activity for production of C5a and C3a. Immunol. Lett. 1991, 27, 49-52.
192. Fujita, Y.; Inoue, I.; Inagi, R.; Miyata, T.; Shinzato, T.; Sugiyama, S.; Miyama, A.; Maeda, K. Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia. Nippon Jinzo Gakkai Shi 1993, 35, 393-7.
193. Kitagawa, M.; Naruse, S.; Ishiguro, H.; Hayakawa, T. Pharmaceutical development for treating pancreatic diseases. Pancreas 1998, 16, 427-31.
194. Love, R. A.; Parge, H. E.; Wickersham, J. A.; Hostomsky, Z.; Habuka, N.; Moomaw, E. W.; Adachi, T.; Margosiak, S.; Dagostino, E.; Hostomska, Z. The conformation of hepatitis C virus NS3 proteinase with and without NS4A: a structural basis for the activation of the enzyme by its cofactor. Clin. Diagn. Virol. 1998, 10, 151-6.
195. Yan, Y.; Li, Y.; Munshi, S.; Sardana, V.; Cole, J. L.; Sardana, M.; Steinkuehler, C.; Tomei, L.; De Francesco, R.; Kuo, L. C.; Chen, Z. Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form. Protein Sci. 1998, 7, 837-47.
196. Koch, J. O.; Bartenschlager, R. Determinants of substrate specificity in the NS3 serine proteinase of the hepatitis C virus. Virology 1997, 237, 78-88.
197. Zhang, R.; Durkin, J.; Windsor, W. T.; McNemar, C.; Ramanathan, L.; Le, H. V. Probing the substrate specificity of hepatitis C virus NS3 serine protease by using synthetic peptides. J. Virol. 1997, 71, 6208-13.
198. Sudo, K.; Matsumoto, Y.; Matsushima, M.; Fujiwara, M.; Konno, K.; Shimotohno, K.; Shigeta, S.; Yokota, T. Novel hepatitis C virus protease inhibitors: thiazolidine derivatives. Biochem. Biophys. Res. Commun. 1997, 238, 643-7.
199. Kakiuchi, N.; Komoda, Y.; Komoda, K.; Takeshita, N.; Okada, S.; Tani, T.; Shimotohno, K. Non-peptide inhibitors of HCV serine proteinase. FEBS Lett. 1998, 421, 217-20.
200. Steinkuhler, C.; Biasiol, G.; Brunetti, M.; Urbani, A.; Koch, U.; Cortese, R.; Pessi, A.; De Francesco, R. Product inhibition of the hepatitis C virus NS3 protease. Biochemistry 1998, 37, 8899-905.
201. Llinas-Brunet, M.; Bailey, M.; Fazal, G.; Goulet, S.; Halmos, T.; Laplante, S.; Maurice, R.; Poirier, M.; Poupart, M. A.; Thibeault, D.; Wernic, D.; Lamarre, D. Peptide-based inhibitors of the hepatitis C virus serine protease. Bioorg. Med. Chem. Lett. 1998, 8, 1713-8.
202. Llinas-Brunet, M.; Bailey, M.; Deziel, R.; Fazal, G.; Gorys, V.; Goulet, S.; Halmos, T.; Maurice, R.; Poirier, M.; Poupart, M. A.; Rancourt, J.; Thibeault, D.; Wernic, D.; Lamarre, D. Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease. Bioorg. Med. Chem. Lett. 1998, 8, 2719-24.
203. Ingallinella, P.; Altamura, S.; Bianchi, E.; Taliani, M.; Ingenito, R.; Cortese, R.; De Francesco, R.; Steinkuhler, C.; Pessi, A. Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by optimizing the cleavage products. Biochemistry 1998, 37, 8906-14.
204. Davis, R.; Whittington, R. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery. Drugs 1995, 49, 954-83.
205. Robert, S.; Wagner, B. K. J.; Boulanger, M.; Richer, M. Aprotinin. Ann. Pharmacother. 1996, 30, 372-80.
206. Smith, C. R. Management of bleeding complications in redo cardiac operations. Ann. Thorac. Surg. 1998, 65 (Suppl. S), S2-S8.
207. Pouard, P. Review of efficacy parameters. Ann. Thorac. Surg. 1998, 65 (Suppl. S), S40-S43.
208. Dobkowski, W. B.; Murkin, J. M. A risk-benefit assessment of aprotinin in cardiac surgical procedures. Drug Saf. 1998, 18, 21-41.
209. Royston, D. Aprotinin versus lysine analogues: The debate continues. Ann. Thorac. Surg. 1998, 65 (Suppl. S), S9-S19.
210. Rich, J. B. The efficacy and safety of aprotinin use in cardiac surgery. Ann. Thorac. Surg. 1998, 66, S6-11 (discussion S25-8).
211. Llamas, P.; Cabrera, R.; Gomez-Arnau, J.; Fernandez, M. N. Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin. Haematologica 1998, 83, 338-46.
212. Pezzilli, R.; Barakat, B.; MorselliLabate, A. M. Evaluation of the immunomodulatory effect of gabexate mesilate in patients with severe acute pancreatitis. Curr. Ther. Res. Clin. Exp. 1998, 59, 710-6.
213. Okumura, Y.; Inoue, H.; Fujiyama, Y.; Bamba, T. Effects of serine protease inhibitors on accumulation of polymorphonuclear leukocytes in the lung induced by acute pancreatitis in rats. J. Gastroenterol. 1995, 30, 379-86.
214. Parodi, F.; Cordero, G.; DeGasperis, C.; Minola, P.; Dellora, C.; Innocenti, P. Gabexate mesilate, a new synthetic serine protease inhibitor: A pilot clinical trial in valvular heart surgery. J. Cardiothorac. Vasc. Anesth. 1996, 10, 235-7.
215. Shibata, T.; Yamamoto, F.; Suchiro, S.; Kinoshita, H. Effects of protease inhibitors on postischemic recovery of the heart. Cardiovasc. Drugs Ther. 1997, 11, 547-56.
216. Lee, S. L.; Alexander, R. S.; Smallwood, A.; Trievel, R.; Mersinger, L.; Weber, R. C.; Kettner, C. New inhibitors of thrombin and other trypsin-like proteases: hydrogen bonding of an aromatic cyano group with a backbone amide of the P1 binding site replaces binding of a basic side chain. Biochemistry 1997, 36, 13180-6.
217. Sanderson, P. E. Small, noncovalent serine protease inhibitors. Med. Res. Rev. 1999, 19, 179-97.
218. Tucker, T. J.; Brady, S. F.; Lumma, W. C.; Lewis, S. D.; Gardell, S. J.; Naylor-Olsen, A. M.; Yan, Y.; Sisko, J. T.; Stauffer, K. J.; Lucas, B. J.; Lynch, J. J.; Cook, J. J.; Stranieri, M. T.; Holahan, M. A.; Lyle, E. A.; Baskin, E. P.; Chen, I. W.; Dancheck, K. B.; Krueger, J. A.; Cooper, C. M.; Vacca, J. P. Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position. J. Med. Chem. 1998, 41, 3210-9.
219. Lyle, T. A.; Chen, Z.; Appleby, S. D.; Freidinger, R. M.; Gardell, S. J.; Lewis, S. D.; Li, Y.; Lyle, E. A.; Lynch, J. J. J.; Mulichak, A. M.; Ng, A. S.; Naylor-Olsen, A. M.; Sanders, W. M. Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor. Bioorg. Med. Chem. Lett. 1997, 7, 67-72.
220. Otto, H.-H.; Schirmeister, T. Cysteine proteases and their inhibitors. Chem. Rev. 1997, 97, 133-71.
221. Rasnick, D. Small synthetic inhibitors of cysteine proteases. Perspect. Drug Discov. Des. 1996, 6, 47-63.
222. Rawlings, N. D.; Barrett, A. J. Families of cysteine peptidases. Methods Enzymol. 1994, 244, 461-86.
223. Rotonda, J.; Nicholson, D. W.; Fazil, K. M.; Gallant, M.; Gareau, Y.; Labelle, M.; Peterson, E. P.; Rasper, D. M.; Ruel, R.; Vaillancourt, J. P.; Thornberry, N. A.; Becker, J. W. The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat. Struct. Biol. 1996, 3, 619-25.
224. Drake, F. H.; Dodds, R. A.; James, I. E.; Connor, J. R.; Debouck, C.; Richardson, S.; LeeRykaczewski, E.; Coleman, L.; Rieman, D.; Barthlow, R.; Hastings, G.; Gowen, M. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J. Biol. Chem. 1996, 271, 12511-6.
225. Votta, B. J.; Levy, M. A.; Badger, A.; Bradbeer, J.; Dodds, R. A.; James, I. E.; Thompson, S.; Bossard, M. J.; Carr, T.; Connor, J. R.; Tomaszek, T. A.; Szewczuk, L.; Drake, F. H.; Veber, D. F.; Gowen, M. Peptide aldehyde inhibitors of cathepsin K inhibit bone resorption both in vitro and in vivo. J. Bone Miner. Res. 1997, 12, 1396-406.
226. Yamashita, D. S.; Smith, W. W.; Zhao, B. G.; Janson, C. A.; Tomaszek, T. A.; Bossard, M. J.; Levy, M. A.; Oh, H. J.; Carr, T. J.; Thompson, S. K.; Ijames, C. F.; Carr, S. A.; McQueney, M.; Dalessio, K. J.; Amegadzie, B. Y.; Hanning, C. R.; AbdelMeguid, S.; DesJarlais, R. L.; Gleason, J. G.; Veber, D. F. Structure and design of potent and selective cathepsin K inhibitors. J. Am. Chem. Soc. 1997, 119, 11351-2.
227. Thompson, S. K.; Halbert, S. M.; Bossard, M. J.; Tomaszek, T. A.; Levy, M. A.; Zhao, B. G.; Smith, W. W.; AbdelMeguid, S. S.; Janson, C. A.; Dalessio, K. J.; McQueney, M. S.; Amegadzie, B. Y.; Hanning, C. R.; DesJarlais, R. L.; Briand, J.; Sarkar, S. K.; Huddleston, M. J.; Ijames, C. F.; Carr, S. A.; Garnes, K. T.; Shu, A.; Heys, J. R.; Bradbeer, J.; Zembryki, D.; LeeRykaczewski, L.; James, I. E.; Lark, M. W.; Drake, F. H.; Gowen, M.; Gleason, J. G.; Veber, D. F. Design of potent and selective human cathepsin K inhibitors that span the active site. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 14249-54.
228. DesJarlais, R. L.; Yamashita, D. S.; Oh, H. J.; Uzinskas, I. N.; Erhard, K. F.; Allen, A. C.; Haltiwanger, R. C.; Zhao, B. G.; Smith, W. W.; AbdelMeguid, S. S.; Dalessio, K.; Janson, C. A.; McQueney, M. S.; Tomaszek, T. A.; Levy, M. A.; Veber, D. F. Use of X-ray cocrystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin K. J. Am. Chem. Soc. 1998, 120, 9114-5.
229. Marquis, R. W.; Yamashita, D. S.; Ru, Y.; LoCastro, S. M.; Oh, H. J.; Erhard, K. F.; DesJarlais, R. L.; Head, M. S.; Smith, W. W.; Zhao, B. G.; Janson, C. A.; AbdelMeguid, S. S.; Tomaszek, T. A.; Levy, M. A.; Veber, D. F. Conformationally constrained 1,3-diamino ketones: A series of potent inhibitors of the cysteine protease cathepsin K. J. Med. Chem. 1998, 41, 3563-7.
230. Palmer, J. T.; Rasnick, D.; Klaus, J. L.; Bromme, D. Vinyl sulfones as mechanism-based cysteine protease inhibitors. J. Med. Chem. 1995, 38, 3193-6.
231. Linnevers, C. J.; McGrath, M. E.; Armstrong, R.; Mistry, F. R.; Barnes, M. G.; Klaus, J. L.; Palmer, J. T.; Katz, B. A.; Bromme, D. Expression of human cathepsin K in Pichia pastoris and preliminary crystallographic studies of an inhibitor complex. Protein Sci. 1997, 6, 919-21.
232. Shaw, E.; Wikstrom, P.; Ruscica, J. An exploration of the primary specificity site of cathepsin B. Arch. Biochem. Biophys. 1983, 222, 424-9.
233. Krantz, A.; Copp, L. J.; Coles, P. J.; Smith, R. A.; Heard, S. B. Peptidyl (acyloxy)methyl ketones and the quiescent affinity label concept: the departing group as a variable structural element in the design of inactivators of cysteine proteinases. Biochemistry 1991, 30, 4678-87.
234. Krantz, A. Peptidyl (acyloxy)methanes as quiescent affinity labels for cysteine proteinases. Methods Enzymol. 1994, 244, 656-71.
235. Wagner, B. M.; Smith, R. A.; Coles, P. J.; Copp, L. J.; Ernest, M. J.; Krantz, A. In vivo inhibition of cathepsin B by peptidyl (acyloxy)methyl ketones. J. Med. Chem. 1994, 37, 1833-40.
236. Feng, M. H.; Chan, S. L.; Xiang, Y.; Huber, C. P.; Lim, C. The binding mode of an E-64 analogue to the active site of cathepsin B. Protein Eng. 1996, 9, 977-86.
237. Navab, R.; Mort, J. S.; Brodt, P. Inhibition of carcinoma cell invasion and liver metastases formation by the cysteine proteinase inhibitor E-64. Clin. Exp. Metast. 1997, 15, 121-9.
238. Gour-Salin, B. J.; Lachance, P.; Plouffe, C.; Storer, A. C.; Menard, R. Epoxysuccinyl dipeptides as selective inhibitors of cathepsin B. J. Med. Chem. 1993, 36, 720-5.
239. Tsuchiya, K.; Kohda, Y.; Yoshida, M.; Zhao, L.; Ueno, T.; Yamashita, J.; Yoshioka, T.; Kominami, E.; Yamashima, T. Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors. Exp. Neurol. 1999, 155, 187-94.
240. Yamashima, T.; Kohda, Y.; Tsuchiya, K.; Ueno, T.; Yamashita, J.; Yoshioka, T.; Kominami, E. Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'. Eur. J. Neurosci. 1998, 10, 1723-33.
241. Hill, P. A.; Buttle, D. J.; Jones, S. J.; Boyde, A.; Murata, M.; Reynolds, J. J.; Meikle, M. C. Inhibition of bone resorption by selective inactivators of cysteine proteinases. J. Cell. Biochem. 1994, 56, 118-30.
242. Woo, J. T.; Sigeizumi, S.; Yamaguchi, K.; Sugimoto, K.; Kobori, T.; Tsuji, T.; Kondo, K. Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L. Bioorg. Med. Chem. Lett. 1995, 5, 1501-4.
243. Kirschke, H.; Shaw, E. Rapid interaction of cathepsin L by Z-Phe-PheCHN12 and Z-Phe-AlaCHN2. Biochem. Biophys. Res. Commun. 1981, 101, 454-8.
244. Rifkin, B. R.; Vernillo, A. T.; Kleckner, A. P.; Auszmann, J. M.; Rosenberg, L. R.; Zimmerman, M. Cathepsin B and L activities in isolated osteoclasts. Biochem. Biophys. Res. Commun. 1991, 179, 63-9.
245. Yasuma, T.; Oi, S.; Choh, N.; Nomura, T.; Furuyama, N.; Nishimura, A.; Fujisawa, Y.; Sohda, T. Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption. J. Med. Chem. 1998, 41, 4301-8.
246. Thornberry, N. A.; Rano, T. A.; Peterson, E. P.; Rasper, D. M.; Timkey, T.; Garcia-Calvo, M.; Houtzager, V. M.; Nordstrom, P. A.; Roy, S.; Vaillancourt, J. P.; Chapman, K. T.; Nicholson, D. W. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J. Biol. Chem. 1997, 272, 17907-11.
247. Talanian, R. V.; Quinlan, C.; Trautz, S.; Hackett, M. C.; Mankovich, J. A.; Banach, D.; Ghayur, T.; Brady, K. D.; Wong, W. W. Substrate specificities of caspase family proteases. J. Biol. Chem. 1997, 272, 9677-82.
248. Margolin, N.; Raybuck, S. A.; Wilson, K. P.; Chen, W.; Fox, T.; Gu, Y.; Livingston, D. J. Substrate and inhibitor specificity of interleukin-1 beta-converting enzyme and related caspases. J. Biol. Chem. 1997, 272, 7223-8.
249. Thornberry, N. A. Caspases: key mediators of apoptosis. Chem. Biol. 1998, 5, R97-103.
250. Alnemri, E. S.; Livingston, D. J.; Nicholson, D. W.; Salvesen, G.; Thornberry, N. A.; Wong, W. W.; Yuan, J. Human ICE/CED-3 protease nomenclature [letter]. Cell 1996, 87, 171.
251. Cerretti, D. P.; Kozlosky, C. J.; Mosley, B.; Nelson, N.; Van Ness, K.; Greenstreet, T. A.; March, C. J.; Kronheim, S. R.; Druck, T.; Cannizzaro, L. A.; et al. Molecular cloning of the interleukin-1 beta converting enzyme. Science 1992, 256, 97-100.
252. Talanian, R. V.; Allen, H. J. Roles of caspases in inflammation and apoptosis: Prospects as drug discovery targets. Annu. Rep. Med. Chem. 1998, 33, 273-82.
253. Thornberry, N. A.; Bull, H. G.; Calaycay, J. R.; Chapman, K. T.; Howard, A. D.; Kostura, M. J.; Miller, D. K.; Molineaux, S. M.; Weidner, J. R.; Aunins, J.; et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 1992, 356, 768-74.
254. Chapman, K. T. Synthesis of a potent, reversible inhibitor of interleukin-1β converting enzyme. Bioorg. Med. Chem. Lett. 1992, 2, 613-8.
255. Rano, T. A.; Timkey, T.; Peterson, E. P.; Rotonda, J.; Nicholson, D. W.; Becker, J. W.; Chapman, K. T.; Thornberry, N. A. A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE). Chem. Biol. 1997, 4, 149-55.
256. Dolle, R. E.; Singh, J.; Rinker, J.; Hoyer, D.; Prasad, C. V.; Graybill, T. L.; Salvino, J. M.; Helaszek, C. T.; Miller, R. E.; Ator, M. A. Aspartyl alpha-((1-phenyl-3-(trifluoromethyl)-pyrazol-5-yl)oxy)methyl ketones as interleukin-1 beta converting enzyme inhibitors. Significance of the P1 and P3 amido nitrogens for enzyme-peptide inhibitor binding. J. Med. Chem. 1994, 37, 3863-6.
257. Ku, G.; Faust, T.; Lauffer, L. L.; Livingston, D. J.; Harding, M. W. Interleukin-1 beta converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine 1996, 8, 377-86.
258. Norman, J.; Yang, J.; Fink, G.; Carter, G.; Ku, G.; Denham, W.; Livingston, D. Severity and mortality of experimental pancreatitis are dependent on interleukin-1 converting enzyme (ICE). J. Interferon Cytokine Res. 1997, 17, 113-8.
259. Dolle, R. E.; Prouty, C. P.; Prasad, C. V.; Cook, E.; Saha, A.; Ross, T. M.; Salvino, J. M.; Helaszek, C. T.; Ator, M. A. First examples of peptidomimetic inhibitors of interleukin-1 beta converting enzyme. J. Med. Chem. 1996, 39, 2438-40.
260. Golec, J. M.; Mullican, M. D.; Murcko, M. A.; Wilson, K. P.; Kay, D. P.; Jones, S. D.; Murdoch, R.; Bemis, G. W.; Raybuck, S. A.; Luong, Y. P.; Livingston, D. J. Structure-based design of nonpeptidic pyridone aldehydes as inhibitors of interleukin-1β converting enzyme. Bioorg. Med. Chem. Lett. 1997, 7, 2181-6.
261. Semple, G.; Ashworth, D. M.; Baker, G. R.; Batt, A. R.; Baxter, A. J.; Benzies, D. W.; Elliot, L. H.; Evans, D. M.; Franklin, R. J.; Hudson, P.; Jenkins, P. D.; Pitt, G. R.; Rooker, D. P.; Sheppard, A.; Szelke, M.; Yamamoto, S.; Isomura, Y. Pyridone-based peptidomimetic inhibitors of interleukin-1β-converting enzyme (ICE). Bioorg. Med. Chem. Lett. 1997, 7, 1337-42.
262. Semple, G.; Ashworth, D. M.; Batt, A. R.; Baxter, A. J.; Benzies, D. W.; Elliot, L. H.; Evans, D. M.; Franklin, R. J.; Hudson, P.; Jenkins, P. D.; Pitt, G. R.; Rooker, D. P.; Yamamoto, S.; Isomura, Y. Peptidomimetic aminomethylene ketone inhibitors of interleukin-1 beta-converting enzyme (ICE). Bioorg. Med. Chem. Lett. 1998, 8, 959-64.
263. Dolle, R. E.; Prasad, C. V.; Prouty, C. P.; Salvino, J. M.; Awad, M. M.; Schmidt, S. J.; Hoyer, D.; Ross, T. M.; Graybill, T. L.; Speier, G. J.; Uhl, J.; Miller, B. E.; Helaszek, C. T.; Ator, M. A. Pyridazinodiazepines as a high-affinity, P2-P3 peptidomimetic class of interleukin-1 beta-converting enzyme inhibitor. J. Med. Chem. 1997, 40, 1941-6.
264. Karanewsky, D. S.; Bai, X.; Linton, S. D.; Krebs, J. F.; Wu, J.; Pham, B.; Tomaselli, K. J. Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain). Bioorg. Med. Chem. Lett. 1998, 8, 2757-62.
265. Chinnaiyan, A. M.; Dixit, V. M. The cell-death machine. Curr. Biol. 1996, 6, 555-62.
266. Cohen, G. M. Caspases: the executioners of apoptosis. Biochem. J. 1997, 326, 1-16.
267. Garcia-Calvo, M.; Peterson, E. P.; Leiting, B.; Ruel, R.; Nicholson, D. W.; Thornberry, N. A. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J. Biol. Chem. 1998, 273, 32608-13.
268. Nicholson, D. W.; Ali, A.; Thornberry, N. A.; Vaillancourt, J. P.; Ding, C. K.; Gallant, M.; Gareau, Y.; Griffin, P. R.; Labelle, M.; Lazebnik, Y. A.; et al. Identification and inhibition of the ICE/ CED-3 protease necessary for mammalian apoptosis. Nature 1995, 376, 37-43.
269. Mittl, P. R.; Di Marco, S.; Krebs, J. F.; Bai, X.; Karanewsky, D. S.; Priestle, J. P.; Tomaselli, K. J.; Grutter, M. G. Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone. J. Biol. Chem. 1997, 272, 6539-47.
270. Couch, R. B. Rhinoviruses. In Virology; Fields, B. N., Knipe, D. M., Eds.; Raven Press: New York, 1990; pp 607-629.
271. Rueckert, P. R. Piconaviridae and their replication. In Virology; Fields, B. N., Knipe, D. M., Eds.; Raven Press: New York, 1990; pp 507-548.
272. Diana, G. D.; Pevear, D. C. Antipicornavirus drugs: current status; International Medical Press Ltd.: London, 1997; pp 401-408.
273. Matthews, D. A.; Smith, W. W.; Ferre, R. A.; Condon, B.; Budahazi, G.; Sisson, W.; Villafranca, J. E.; Janson, C. A.; McElroy, H. E.; Gribskov, C. L.; et al. Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. Cell 1994, 77, 761-71.
274. Matthews, D.; Smith, W. W.; Ferre, R. A.; Condon, B.; Budahazi, G.; Sisson, W.; Villafranca, J. E.; Janson, C.; McElroy, H.; Gribskov, C.; Worland, S. Crystal-Structure Of Human Rhinovirus Type-14 3c-Protease. J. Cell. Biochem. 1994 (Suppl. 18D), 170.
275. Webber, S. E.; Okano, K.; Little, T. L.; Reich, S. H.; Xin, Y.; Fuhrman, S. A.; Matthews, D. A.; Love, R. A.; Hendrickson, T. F.; Patick, A. K.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Ford, C. E.; Binford, S. L.; Worland, S. T. Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: Design, synthesis, biological evaluation, and cocrystal structure solution of P-1 glutamine isosteric replacements. J. Med. Chem. 1998, 41, 2786-805.
276. Webber, S. E.; Tikhe, J.; Worland, S. T.; Fuhrman, S. A.; Hendrickson, T. F.; Matthews, D. A.; Love, R. A.; Patick, A. K.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; DeLisle, D. M.; Ford, C. E.; Binford, S. L. Design, synthesis, and evaluation of nonpeptidic inhibitors of human rhinovirus 3C protease. J. Med. Chem. 1996, 39, 5072-82.
277. Molla, A.; Hellen, C. U.; Wimmer, E. Inhibition of proteolytic activity of poliovirus and rhinovirus 2A proteinases by elastase-specific inhibitors. J. Virol. 1993, 67, 4688-95.
278. Venkatraman, S.; Kong, J.; Nimkar, S.; Wang, Q. M.; Aube, J.; Hanzlik, R. P. Design, synthesis, and evaluation of azapeptides as substrates and inhibitors for human rhinovirus 3C protease. Bioorg. Med. Chem. Lett. 1999, 9, 577-80.
279. Kati, W. M.; Sham, H. L.; McCall, J. O.; Montgomery, D. A.; Wang, G. T.; Rosenbrook, W.; Miesbauer, L.; Buko, A.; Norbeck, D. W. Inhibition of 3C protease from human rhinovirus strain 1B by peptidyl bromomethyl ketonehydrazides. Arch. Biochem. Biophys. 1999, 362, 363-75.
280. Kong, J. S.; Venkatraman, S.; Furness, K.; Nimkar, S.; Shepherd, T. A.; Wang, Q. M.; Aube, J.; Hanzlik, R. P. Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication. J. Med. Chem. 1998, 41, 2579-87.
281. Dragovich, P. S.; Zhou, R.; Skalitzky, D. J.; Fuhrman, S. A.; Patick, A. K.; Ford, C. E.; Meador, J. W., 3rd; Worland, S. T. Solid-phase synthesis of irreversible human rhinovirus 3C protease inhibitors. Part 1: Optimization of tripeptides incorporating N-terminal amides. Bioorg. Med. Chem. 1999, 7, 589-98.
282. Dragovich, P. S.; Webber, S. E.; Babine, R. E.; Fuhrman, S. A.; Patick, A. K.; Matthews, D. A.; Lee, C. A.; Reich, S. H.; Prins, T. J.; Marakovits, J. T.; Littlefield, E. S.; Zhou, R.; Tikhe, J.; Ford, C. E.; Wallace, M. B.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Binford, S. L.; Harr, J. E. V.; DeLisle, D. M.; Worland, S. T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies. J. Med. Chem. 1998, 41, 2806-18.
283. Dragovich, P. S.; Webber, S. E.; Babine, R. E.; Fuhrman, S. A.; Patick, A. K.; Matthews, D. A.; Reich, S. H.; Marakovits, J. T.; Prins, T. J.; Zhou, R.; Tikhe, J.; Littlefield, E. S.; Bleckman, T. M.; Wallace, M. B.; Little, T. L.; Ford, C. E.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Binford, S. L.; DeLisle, D. M.; Worland, S. T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure-activity studies. J. Med. Chem. 1998, 41, 2819-34.
284. Dragovich, P. S.; Prins, T. J.; Zhou, R.; Fuhrman, S. A.; Patick, A. K.; Matthews, D. A.; Ford, C. E.; Meador, J. W., 3rd; Ferre, R. A.; Worland, S. T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 3. Structure-activity studies of ketomethylene-containing peptidomimetics. J. Med. Chem. 1999, 42, 1203-12.
285. Dragovich, P. S.; Prins, T. J.; Zhou, R.; Webber, S. E.; Marakovits, J. T.; Fuhrman, S. A.; Patick, A. K.; Matthews, D. A.; Lee, C. A.; Ford, C. E.; Burke, B. J.; Rejto, P. A.; Hendrickson, T. F.; Tuntland, T.; Brown, E. L.; Meador, J. W., 3rd; Ferre, R. A.; Harr, J. E.; Kosa, M. B.; Worland, S. T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements. J. Med. Chem. 1999, 42, 1213-24.
286. Matthews, D. A.; Dragovich, P. S.; Webber, S. E.; Fuhrman, S. A.; Patick, A. K.; Zalman, L. S.; Hendrickson, T. F.; Love, R. A.; Prins, T. J.; Marakovits, J. T.; Zhou, R.; Tikhe, J.; Ford, C. E.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Binford, S. L.; Brothers, M. A.; DeLisle, D. M.; Worland, S. T. Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11000-7.
287. Patick, A. K.; Binford, S. L.; Brothers, M. A.; Jackson, R. L.; Ford, C. E.; Diem, M. D.; Maldonado, F.; Dragovich, P. S.; Zhou, R.; Prins, T. J.; Fuhrman, S. A.; Meador, J. W.; Zalman, L. S.; Matthews, D. A.; Worland, S. T. In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease [in process citation]. Antimicrob. Agents Chemother. 1999, 43, 2444-50.
288. Johnson, P. Calpains (intracellular calcium-activated cysteine proteinases): structure-activity relationships and involvement in normal and abnormal cellular metabolism. Int. J. Biochem. 1990, 22, 811-22.
289. Saido, T. C.; Sorimachi, H.; Suzuki, K. Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J. 1994, 8, 814-22.
290. Wang, K. K. Developing selective inhibitors of calpain. Trends Pharmacol. Sci. 1990, 11, 139-42.
291. Wang, K. K.; Yuen, P. W. Calpain inhibition: an overview of its therapeutic potential. Trends Pharmacol. Sci. 1994, 15, 412-9.
292. Iqbal, M.; Messina, P. A.; Freed, B.; Das, M.; Chatterjee, S.; Tripathy, R.; Tao, M.; Josef, K. A.; Dembofsky, B.; Dunn, D.; Griffith, E.; Siman, R.; Senadhi, S.; Biazzo, W.; Bozyczko-Coyne, D.; Meyer, S. L.; Ator, M. A.; Bihovsky, R. Subsite requirements for peptide aldehyde inhibitors of human calpain I. Bioorg. Med. Chem. Lett. 1997, 7, 539-44.
293. Mehdi, S.; Angelastro, M. R.; Wiseman, J. S.; Bey, P. Inhibition of the proteolysis of rat erythrocyte membrane proteins by a synthetic inhibitor of calpain [published erratum appears in Biochem. Biophys. Res. Commun. 1989, 759, 371]. Biochem. Biophys. Res. Commun. 1988, 157, 1117-23.
294. Ariyoshi, H.; Shiba, E.; Kambayashi, J.; Sakon, M.; Tsujinaka, T.; Uemura, Y.; Mori, T. Characteristics of various synthetic peptide calpain inhibitors and their application for the analysis of platelet reaction. Biochem. Int. 1991, 23, 1019-33.
295. Tripathy, R.; Gu, Z. Q.; Dunn, D.; Senadhi, S. E.; Ator, M. A.; Chatterjee, S. P2-proline-derived inhibitors of calpain I. Bioorg. Med. Chem. Lett. 1998, 8, 2647-52.
296. Angliker, H.; Anagli, J.; Shaw, E. Inactivation of calpain by peptidyl fluoromethyl ketones. J. Med. Chem. 1992, 35, 216-20.
297. Chatterjee, S.; Ator, M. A.; Bozyczko-Coyne, D.; Josef, K.; Wells, G.; Tripathy, R.; Iqbal, M.; Bihovsky, R.; Senadhi, S. E.; Mallya, S.; O'Kane, T. M.; McKenna, B. A.; Siman, R.; Mallamo, J. P. Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I. J. Med. Chem. 1997, 40, 3820-8.
298. Chatterjee, S.; Josef, K.; Wells, G.; Iqbal, M.; Bihovsky, R.; Mallamo, J. P.; Ator, M. A.; Bozyczko-Coyne, D.; Mallya, S.; Senadhi, S.; Siman, R. Potent fluoromethyl ketone inhibitors of recombinant human calpain I. Bioorg. Med. Chem. Lett. 1996, 6, 1237-40.
299. Bartus, R. T.; Hayward, N. J.; Elliott, P. J.; Sawyer, S. D.; Baker, K. L.; Dean, R. L.; Akiyama, A.; Straub, J. A.; Harbeson, S. L.; Li, Z.; et al. Calpain inhibitor AK295 protects neurons from focal brain ischemia. Effects of postocclusion intra-arterial administration. Stroke 1994, 25, 2265-70.
300. Li, Z.; Ortega-Vilain, A. C.; Patil, G. S.; Chu, D. L.; Foreman, J. E.; Eveleth, D. D.; Powers, J. C. Novel peptidyl alpha-keto amide inhibitors of calpains and other cysteine proteases. J. Med. Chem. 1996, 39, 4089-98.
301. Adang-Aep; Hermkens, P. H. H.; Linders, J. T. M.; Ottenheijm, H. C. J.; Vanstaveren, C. J. Case-histories of peptidomimetics - Progression from peptides to drugs. Recl. Trav. Chim. Pays Bas J. R. Netherlands Chem. Soc. 1994, 113, 63-78.
302. Gante, J. Peptidomimetics - Tailored Enzyme-Inhibitors. Angew. Chem. Int. Ed. Engl. 1994, 33, 1699-720.
303. Brogden, R. N.; Wiseman, L. R. Moexipril. A review of its use in the management of essential hypertension. Drugs 1998, 55, 845-60.
304. Peters, D. C.; Noble, S.; Plosker, G. L. Trandolapril. An update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs 1998, 56, 871-93.
305. Giusti, A.; Bertolotti, M.; Llabres, S.; Carre, A.; Casini, A. Comparison of the efficacy of zofenopril or enalapril in patients with mild to moderate hypertension. Am. J. Hypertens. 1999, 12, 26A-27A.
306. White, M. C. Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy 1998, 18, 588-99.
307. Pruitt, J. R.; Olson, R. E. Angiotensin II receptor antagonists: Design, SAR and development of Losartan. In Medicinal Chemistry of the Renin-Angiotensin System; Timmermans, P. B. M. W. M., Wexler, R. R., Eds.; Elsevier Science: New York, 1994; pp 121-155.
308. Gillis, J. C.; Markham, A. Irbesartan. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension. Drugs 1997, 54, 885-902.
309. McClellan, K. J.; Goa, K. L. Candesartan cilexetil. A review of its use in essential hypertension. Drugs 1998, 56, 847-69.
310. Vachharajani, N. N.; Shyu, W. C.; Chando, T. J.; Everett, D. W.; Greene, D. S.; Barbhaiya, R. H. Oral bioavailability and disposition characteristics of irbesartan, an angiotensin antagonist, in healthy volunteers. J. Clin. Pharmacol. 1998, 38, 702-7.
311. Pylypchuk, G. B. ACE inhibitor-versus angiotensin II blocker-induced cough and angioedema. Ann. Pharmacother. 1998, 32, 1060-6.
312. Roques, B. P.; Noble, F.; Dauge, V.; Fournie-Zaluski, M. C.; Beaumont, A. Neutral endopeptidase 24.11; structure, inhibition, and experimental and clinical pharmacology. Pharmacol. Rev. 1993, 45, 87-146.
313. Schwartz, J. C.; Gros, C.; Lecomte, J. M.; Bralet, J. Enkephalinase (EC 3.4.24.11) inhibitors: protection of endogenous ANF against inactivation and potential therapeutic applications. Life Sci. 1990, 47, 1279-97.
314. Richards, A. M.; Wittert, G. A.; Crozier, I. G.; Espiner, E. A.; Yandle, T. G.; Ikram, H.; Frampton, C. Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angiotensin II. J. Hypertens. 1993, 11, 407-16.
315. Flynn, G. A.; French, G. F.; Dage, R. C. Dual inhibitors of angiotensin converting enzyme and neutral endopeptidase: Design and therapeutic rationale. In Hypertension: Pathology, Diagnosis, and Management; Laragh. J. H., Brenner, B. M., Eds.; Raven Press: New York, 1995; pp 3099-114.
316. French, J. F.; Anderson, B. A.; Downs, T. R.; Dage, R. C. Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase in rats with hypertension. J. Cardiovasc. Pharmacol. 1995, 26, 107-13.
317. Gros, C.; Noel, N.; Souque, A.; Schwartz, J. C.; Danvy, D.; Plaquevent, J. C.; Duhamel, L.; Duhamel, P.; Lecomte, J. M.; Bralet, J. Mixed inhibitors of angiotensin-converting enzyme (EC 3.4.15.1) and enkephalinase (EC 3.4.24.11): rational design, properties, and potential cardiovascular applications of glycopril and alatriopril. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 4210-4.
318. Marie, C.; Mossiat, C.; Lecomte, J. M.; Bralet, J. Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral endopeptidase and angiotensin I-converting enzyme, in rats with heart failure. Pharmacology 1998, 56, 291-6.
319. Wallis, E. J.; Ramsay, L. E.; Hettiarachchi, J. Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension. Clin. Pharmacol. Ther. 1998, 64, 439-49.
320. Robl, J. A.; Sun, C. Q.; Stevenson, J.; Ryono, D. E.; Simpkins, L. M.; Cimarusti, M. P.; Dejneka, T.; Slusarchyk, W. A.; Chao, S.; Stratton, L.; Misra, R. N.; Bednarz, M. S.; Asaad, M. M.; Cheung, H. S.; Abboa-Offei, B. E.; Smith, P. L.; Mathers, P. D.; Fox, M.; Schaeffer, T. R.; Seymour, A. A.; Trippodo, N. C. Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase. J. Med. Chem. 1997, 40, 1570-7.
321. Trippodo, N. C.; Robl, J. A.; Asaad, M. M.; Fox, M.; Panchal, B. C.; Schaeffer, T. R. Effects of omapatrilat in low, normal, and high renin experimental hypertension. Am. J. Hypertens. 1998, 11, 363-72.
322. Burnett, J. C., Jr. Vasopeptidase inhibition: a new concept in blood pressure management. J. Hypertens. Suppl. 1999, 17, S37-43.
323. Robl, J. A.; Sulsky, R.; Sieber-McMaster, E.; Ryono, D. E.; Cimarusti, M. P.; Simpkins, L. M.; Karanewsky, D. S.; Chao, S.; Asaad, M. M.; Seymour, A. A.; Fox, M.; Smith, P. L.; Trippodo, N. C. Vasopeptidase inhibitors: incorporation of geminal and spirocyclic substituted azepinones in mercaptoacyl dipeptides. J. Med. Chem. 1999, 42, 305-11.
324. Arner, E. C.; Pratta, M. A.; Trzaskos, J. M.; Decicco, C. P.; Tortorella, M. D. Generation and characterization of aggrecanase. A soluble, cartilage-derived aggrecan-degrading activity. J. Biol. Chem. 1999, 274, 6594-601.
325. Arner, E. C.; Pratta, M. A.; Decicco, C. P.; Xue, C. B.; Newton, R. C.; Trzaskos, J. M.; Magolda, R. L.; Tortorella, M. D. Aggrecanase. A target for the design of inhibitors of cartilage degradation [in process citation]. Ann. N. Y. Acad. Sci. 1999, 878, 92-107.
326. Bode, W.; Fernandez-Catalan, C.; Tschesche, H.; Grams, F.; Nagase, H.; Maskos, K. Structural properties of matrix metalloproteinases. Cell. Mol. Life Sci. 1999, 55, 639-52.
327. Whittaker, M.; Brown, P. Recent advances in matrix metalloproteinase inhibitor research and development. Curr. Opin. Drug Discov. Dev. 1998, 1, 157-64.
328. Summers, J. B.; Davidsen, S. K. Matrix metalloproteinase inhibitors and cancer. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: Michigan, 1998; Vol. 33, pp 131-40.
329. Becker, J. W.; Marcy, A. I.; Rokosz, L. L.; Axel, M. G.; Burbaum, J. J.; Fitzgerald, P. M.; Cameron, P. M.; Esser, C. K.; Hagmann, W. K.; Hermes, J. D.; et al. Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme. Protein Sci. 1995, 4, 1966-76.
330. Nelson, N. J. Inhibitors of angiogenesis enter phase III testing [news]. J. Natl. Cancer Inst. 1998, 90, 960-3.
331. MacPherson, L. J.; Bayburt, E. K.; Capparelli, M. P.; Carroll, B. J.; Goldstein, R.; Justice, M. R.; Zhu. L.; Hu, S.; Melton, R. A.; Fryer, L.; Goldberg, R. L.; Doughty, J. R.; Spirito, S.; Blancuzzi, V.; Wilson, D.; O'Byrne, E. M.; Ganu, V.; Parker, D. T. Discovery of CGS 27023A, a nonpeptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits. J. Med. Chem. 1997, 40, 2525-32.
332. Santos, O.; McDermott, C. D.; Daniels, R. G.; Appelt, K. Rodent pharmacokinetic and antitumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases. Clin. Exp. Metast. 1997, 15, 499-508.
333. Brewster, M.; Lewis, E. J.; Wilson, K. L.; Greenham, A. K.; Bottomley, K. M. Ro 32-3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis. Arthritis Rheum. 1998, 47, 1639-44.
334. Lewis, E. J.; Bishop, J.; Bottomley, K. M.; Bradshaw, D.; Brewster, M.; Broadhurst, M. J.; Brown, P. A.; Budd, J. M.; Elliott, L.; Greenham, A. K.; Johnson, W. H.; Nixon, J. S.; Rose, F.; Sutton, B.; Wilson, K. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo. Br. J. Pharmacol. 1997, 121, 540-6.
335. Pikul, S.; McDow Dunham, K. L.; Almstead, N. G.; De, B.; Natchus, M. G.; Anastasio, M. V.; McPhail, S. J.; Snider, C. E.; Taiwo, Y. O.; Rydel, T.; Dunaway, C. M.; Gu, F.; Mieling, G. E. Discovery of potent, achiral matrix metalloproteinase inhibitors. J. Med. Chem. 1998, 41, 3568-71.
336. Cherney, R. J.; Wang, L.; Meyer, D. T.; Xue, C. B.; Arner, E. C.; Copeland, R. A.; Covington, M. B.; Hardman, K. D.; Wasserman, Z. R.; Jaffee, B. D.; Decicco. C. P. Macrocyclic hydroxamate inhibitors of matrix metalloproteinases and TNF-alpha production [in process citation]. Bioorg. Med. Chem. Lett. 1999, 9, 1279-84.
337. Reiter, L. A.; Rizzi, J. P.; Pandit, J.; Lasut, M. J.; McGahee, S. M.; Parikh, V. D.; Blake, J. F.; Danley, D. E.; Laird, E. R.; Lopez-Anaya, A.; Lopresti-Morrow, L. L.; Mansour, M. N.; Martinelli, G. J.; Mitchell, P. G.; Owens, B. S.; Pauly, T. A.; Reeves, L. M.; Schulte, G. K.; Yocum, S. A. Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket. Bioorg. Med. Chem. Lett. 1999, 9, 127-32.
338. Jacobsen, E. J.; Mitchell, M. A.; Hendges, S. K.; Belonga, K. L.; Skaletzky, L. L.; Stelzer, L. S.; Lindberg, T. J.; Fritzen, E. L.; Schostarez, H. J.; O'Sullivan, T. J.; Maggiora, L. L.; Stuchly, C. W.; Laborde, A. L.; Kubicek, M. F.; Poorman, R. A.; Beck, J. M.; Miller, H. R.; Petzold, G. L.; Scott, P. S.; Truesdell, S. E.; Wallace, T. L.; Wilks, J. W.; Fisher, C.; Goodman, L. V.; Kaytes, P. S.; et al. Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J. Med. Chem. 1999, 42, 1525-36.
339. Burnouf, C.; Pruniaux, M. P.; Szilagyi, C. M. Phosphodiesterase 4 inhibitors. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: Michigan, 1998; Vol. 33, pp 91-109.
340. Groneberg, R. D.; Burns, C. J.; Morrissette, M. M.; Ullrich, J. W.; Morris, R. L.; Darnbrough, S.; Djuric, S. W.; Condon, S. M.; McGeehan, G. M.; Labaudiniere, R.; Neuenschwander, K.; Scotese, A. C.; Kline, J. A. Dual inhibition of phosphodiesterase 4 and matrix metalloproteinases by an (arylsulfonyl)hydroxamic acid template. J. Med. Chem. 1999, 42, 541-4.
341. Black, R. A.; Rauch, C. T.; Kozlosky, C. J.; Peschon, J. J.; Slack, J. L.; Wolfson, M. F.; Castner, B. J.; Stocking, K. L.; Reddy, P.; Srinivasan, S.; Nelson, N.; Boiani, N.; Schooley, K. A.; Gerhart, M.; Davis, R.; Fitzner, J. N.; Johnson, R. S.; Paxton, R. J.; March, C. J.; Cerretti, D. P. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 1997, 385, 729-33.
342. Vassalli, P. The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 1992, 10, 411-52.
343. Firestein, G. S. Cytokine networks in rheumatoid arthritis: implications for therapy. Agents Actions Suppl. 1995, 47, 37-51.
344. Maini, R. N.; Elliott, M. J.; Brennan, F. M.; Feldmann, M. Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in rheumatoid arthritis (RA) [published erratum appears in Clin. Exp. Immunol. 1995, 702, 443]. Clin. Exp. Immunol. 1995, 101, 207-12.
345. Elliott, M. J.; Maini, R. N.; Feldmann, M.; Long-Fox, A.; Charles, P.; Bijl, H.; Woody, J. N. Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis. Lancet 1994, 344, 1125-7.
346. Newton, R. C.; Decicco, C. P. Therapeutic potential and strategies for inhibiting tumor necrosis factor-alpha. J. Med. Chem. 1999, 42, 2295-314.
347. Maskos, K.; Fernandez-Catalan, C.; Huber, R.; Bourenkov, G. P.; Bartunik, H.; Ellestad, G. A.; Reddy, P.; Wolfson, M. F.; Rauch, C. T.; Castner, B. J.; Davis, R.; Clarke, H. R.; Petersen, M.; Fitzner, J. N.; Cerretti, D. P.; March, C. J.; Paxton, R. J.; Black, R. A.; Bode, W. Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3408-12.
348. Cerretti, D. P. Characterization of the tumour necrosis factor alpha-converting enzyme, TACE/ADAM17. Biochem. Soc. Trans. 1999, 27, 219-23.
349. Mohler, K. M.; Sleath, P. R.; Fitzner, J. N.; Cerretti, D. P.; Alderson, M.; Kerwar, S. S.; Torrance, D. S.; Otten-Evans, C.; Greenstreet, T.; Weerawarna, K.; et al. Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature 1994, 370, 218-20.
350. McGeehan, G. M.; Becherer, J. D.; Bast, R. C., Jr.; Boyer, C. M.; Champion, B.; Connolly, K. M.; Conway, J. G.; Furdon, P.; Karp, S.; Kidao, S.; et al. Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 1994, 370, 558-61.
351. Smithkline Beecham. Hydroxamic acid based inhibitors of the formation of CD23 and TNF. WO-09743250, 1997.
352. Yamazaki, T.; Hinck, A. P.; Wang, Y. X.; Nicholson, L. K.; Torchia, D. A.; Wingfield, P.; Stahl, S. J.; Kaufman, J. D.; Chang, C. H.; Domaille, P. J.; Lam, P. Y. Three-dimensional solution structure of the HIV-1 protease complexed with DMP323, a novel cyclic urea-type inhibitor, determined by nuclear magnetic resonance spectroscopy. Protein Sci. 1996, 5, 495-506.
353. Lam, P. Y.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; et al. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science 1994, 263, 380-4.
354. Erickson, J. W. The not-so-great escape. Nature Struct. Biol. 1995, 2, 523-9.