Non-peptidic Inhibitors of Human Leukocyte Elastase. 4. Design, Synthesis, and in Vitro and in Vivo Activity of a Series of β-Carbolinone-Containing Trifluoromethyl Ketones

Journal of Medicinal Chemistry

Volumn 38, Issue 1, 1995, Pages 86-97

  Veale, Chris A ^a   Damewood, James R ^a   Steelman, Gary B ^a   Bryant, Craig ^a   Gomes, Bruce ^a   Williams, Joseph ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

[4 (4 BROMOPHENYLSULFONYLCARBAMOYL)BENZOYL]VALYLPROLINE N (2 METHYL 1 TRIFLUOROACETYLPROPYL)AMIDE; BETA CARBOLINE DERIVATIVE; CATHEPSIN G; CHYMOTRYPSIN; DIPEPTIDYL CARBOXYPEPTIDASE; ELASTASE INHIBITOR; KETONE DERIVATIVE; LEUKOCYTE ELASTASE; N [4 [(4 CHLOROPHENYLSULFONYL)AMINOCARBONYL]BENZOYL]VALYLPROLYLVALYL TRIFLUOROMETHYL KETONE; PANCREATIC ELASTASE; PAPAIN; THROMBIN; TRYPSIN;

ANIMAL MODEL; ARTICLE; CATTLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; EEL; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; HAMSTER; HUMAN; INFLAMMATION; INHIBITION KINETICS; MOLECULAR DYNAMICS; NEUTROPHIL; NONHUMAN; ORAL DRUG ADMINISTRATION; RABBIT; STRUCTURE ACTIVITY RELATION; SWINE;

AMINO ACID SEQUENCE; ANIMAL; CARBOLINES; HAMSTERS; HUMAN; HYDROCARBONS, FLUORINATED; KETONES; LEUKOCYTE ELASTASE; MOLECULAR SEQUENCE DATA; PANCREATIC ELASTASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029040711     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00001a014     Document Type: Article

References (46)

1. Travis, J.; Dumbin, A.; Potempa, J.; Watorek, W.; Kurdowska, A. Neutrophil Proteinases. Ann. N. Y. Acad. Sci. 1991, 624, 81-86.
2. Homebeck, W.; Soleilhac, J. M.; fixier, J. M.; Moczar, E.; Robert, L. Inhibition by Elastase Inhibitors of the Formyl Met Leu Phe-Induced Chemotaxis of Rat Polymorphonuclear Leukocytes. Cell Biochem. Funct. 1987, 5, 113-122.
3. Banda, M. J.; Rice, A. G.; Griffin, G. L.; Senior, R. M. α1-Proteinase Inhibitor Is a Neutrophil Chemoattractant after Proteolytic Inactivation by Macrophage Elastase. J. Biol. Chem. 1988, 263, 4481-4484.
4. Sandhaus, R. A. Elastase May Play A Central Role in Neutrophil Migration Through Connective Tissue. In Pulmonary Emphysema and Proteolysis; 1986; Taylor, J. C., Mittman, C., Eds.; Academic Press Inc.: New York, 1987; pp 227-234.
5. Sommerhoff, C. P.; Nadel, J. A.; Basbaum, C. B.; Caughey, G. H. Neutrophil Elastase and Cathepsin G Stimulate Secretion from Cultered Bovine Airway Gland Serous Cells. J. Clin. Invest. 1990, 85, 682-689.
6. Sommerhoff, C. P.; Krell, R. D.; Williams, J. C.; Gomes, B. C.; Strimpler, A. M.; Nadel, J. A. Inhibition of Human Neutrophil Elastase by ICI-200, 355. Eur. J. Pharmacol. 1991, 193, 153-158.
7. Gadsek, J. E.; Fells, G. A.; Zimmerman, R. L.; Rennard, S. I.; Crystal, R. G. Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. J. Clin. Invest. 1981, 68, 889-898.
8. Vogelmeier, C.; Hubbard, R. C.; Fells, G. A.; Schnebli, H. P.; Thompson, R. C.; Fritz, H.; Crystal, R. G. Anti-Neutrophil Elastase Defense of the Normal Human Respiratory Epithelial Surface Provided by the Secretory Leukoprotease Inhibitor. J. Clin. Invest. 1991, 87, 482-488.
9. Eriksson, S. The Potential Role of Elastase Inhibitors in Emphysema Treatment. Eur. Respir. J. 1991, 4, 1041-1043.
10. Nadel, J. Role of Mast Cell and Neutrophil Proteases in Airway Secretion. Am. Rev. Respir. Dis. 1991, 144, S48-S51.
11. Jackson, A. H.; Hill, S. L.; Afford, S. C.; Stockley, R. A. Sputum Soluble Phase Proteins and Elastase Activity in Patents with Cystic Fibrosis. J. Respir. Dis. 1984, 65, 114-124.
12. Tosi, M. F.; Zakem, H.; Berger, M. Neutrophil Elastase Cleaves C3bi on Opsonized Pseudomonas as well as CR1 on Neutrophils to Create a Functionally Important Opsonin Receptor Mismatch. J. Clin. Invest. 1990, 86, 300-308.
13. Edwards, P. D.; Bernstein, P. R. Synthetic Inhibitors of Elastase. Med. Res. Rev. 1994, 14, 127-194.
14. Bernstein, P. R.; Edwards, P. D.; Williams, J. C. Inhibitors of Human Leukocyte Elastase. Prog. Med. Chem. 1994, 31, 59-120.
15. Peet, N. P.; Burkhart, J. P.; Angelastro, M. R.; Giroux, E. L.; Mehdi, S.; Bey, P.; Kolb, M.; Neises, B.; Schirlin, D. Synthesis of Peptidyl Fluoromethyl Ketones and Peptidyl α Keto Esters as Inhibitors of Porcine Pancreatic Elastase, Human Neutrophil Elastase, and Rat and Human Neutrophil Cathepsin G. J. Med. Chem. 1990, 33, 394-407.
16. Angelastro, M. R.; Bey, P.; Mehdi, S.; Janusz, M. J.; Peet, N. P. Janus Compounds: Dual Inhibitors of Proteinases Bioorg. Med. Chem. Lett. 1993, 3, 525-530.
17. Doherty, J. B.; Shah, S. K.; Finke, P. E.; Dorn, C. P.; Hagmann, W. K.; Hale, J. J.; Kissinger, A. L.; Thompson, K. R.; Brause, K.; Chandler, G. O.; Knight, W. B.; Matcock, A. L.; Ashe, B. M.; Weston, H.; Gale, P.; Mumford, R. A.; Anderson, O. F.; Williams, H. R.; Nolan, T. E.; Frankenfield, D. L.; Underwood, D.; Vyas, K. P.; Kari, P. H.; Dahlgren, M. E.; Mao, J.; Fletcher, D. S.; Dellea, P. S.; Hand, K. M.; Osinga, D. G.; Peterson, L. B.; Williams, D. T.; Metzger, J. M.; Bonney, R. J.; Humes, J. L.; Pacholok, S. P.; Hanlon, W. A.; Opas, E.; Stolk, J.; Davies, P. Chemical, biochemical, pharmacokinetic, and biological properties of L-680, 833: A potent, orally active monocyclic β-lactam inhibitor of human polymorphonuclear leukocyte elastase Proc. Natl. Acad. Sci. U. SA. 1993, 90, 8727-8731.
18. Bergeson, S.; Schwartz, J. A.; Stein, M. M.; Wildonger, R. A.; Edwards, P. D.; Shaw, A.; Trainor, D. A.; Wolanin, D. J. U. S. Patent 4, 910, 190, 1990; Chem. Abstr. 1991, 114, 123085m.
19. Stein, M. M.; Wildonger, R. A.; Trainor, D. A.; Edwards, P. D.; Yee, Y. K.; Lewis, J. J.; Zottola, M. A.; Williams, J. C.; Strimpler, A. M. In Vitro and In Vivo Inhibition of Human Leukocyte Elastase (HLE) by Two Series of Electrophilic Carbonyl Containing Peptides. In Peptides: Chemistry, Structure, and Biology (Proceedings of the Eleventh American Peptide Symposium); ESCOM Science: Lieden, The Netherlands, 1990; p 369.
20. Williams, J. C.; Falcone, R. C.; Knee, C.; Stein, R. L.; Strimple, A. M.; Reaves, B.; Giles, R. E.; Krell, R. D. Biologie Characterization of ICI-200, 880 and ICI-200, 355, Novel Inhibitors of Human Neutrophil Elastase. Am. Rev. Respir. Dis. 1991, 144, 875-883.
21. Auger, W. R.; Moser, K. M.; Comito, R. M.; Kerr, K. M.; Bernardi, J. L.; Spragg, R. G. Efficacy of ICI 200, 880, in the Prevention of Adult Respiratory Distress Syndrome (ARDS) in Patients undergoing Pulmonary Thromboendarterectomy, (abstract). Am. Respir. Crit. Care Med. 1994, 149 (4), 1032.
22. Gottlieb, J. E.; Elmer, M.; Steiner, R.; Sailer, L.; Minkwitz, M.; Glass, M. Efficacy of Intravenious ICI 200, 880, A Neutrophil Elastase Inhibitor in the Treatment of Adult Respiratory Distress Syndrome (ARDS). Chest 1994, in press.
23. Brown, F. J.; Andisik, D. W.; Bernstein, P. B.; Bryant, C. B.; Ceccarelli, C.; Damewood, J. R., Jr.; Edwards, P. D.; Earley, R. A.; Feeney, S.; Green, R. C.; Gomes, B. C.; Kosmider, B. J.; Krell, R. D.; Shaw, A.; Steelman, G. B.; Thomas, R. M.; Vacek, E. P.; Veale, C. A.; Tuthill, P. A.; Warner, P.; Williams, J. C.; Wolanin, D. J.; Woolson, S. A. The Design of Orally Active, Nonpeptidic Inhibitors of Human Leukocyte Elastase. J. Med. Chem. 1994, 37, 1259-1261.
24. Warner, P.; Green, R. C.; Gomes, B. C.; Williams, J. C. Nonpeptidic Inhibitors of Human Leukocyte Elastase. 1. The Design and Synthesis of Pyridone-Containing Inhibitors. J. Med. Chem. 1994, 37, 3090-3099.
25. Damewood, J. R., Jr.; Edwards, P. D., Feeney, S.; Gomes, B. C.; Steelman, G. B.; Tuthill, P. A.; Williams, J. C.; Warner, P.; Woolson, S. A.; Wolanin, D. J.; Veale, C. A. Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and In Vitro Activity of a Series of 3-Amino-6-arylpyridin-2-one-trifluoromethylke-tones. J. Med. Chem. 1994, 37, 3303-3312.
26. Bernstein, P. B.; Andisik, D.; Bradley, P. K.; Bryant, C. B.; Ceccarelli, C.; Damewood, J. R., Jr.; Earley, R.; Feeney, S.; Gomes, B. C.; Kosmider, B. J.; Steelman, G. B.; Thomas, R. M.; Vacek, E. P.; Veale, C. A.; Williams, J. C.; Wolanin, D. J.; Woolson, S. A. Nonpeptidic Inhibitors of Human Leukocyte Elastase. 3. Design, Synthesis, X-Ray Crystallographic Analysis, and Structure-Activity Relationships for a Series of Orally Active 3-Amino-6-phenylpyridin-2-ones. J. Med. Chem. 1994, 37, 3313-3326.
27. Skiles, J. W.; Sorcek, R.; Jacober, S.; Miao, C.; Mui, P. W.; McNeil, D.; Rosenthal, A. S. Elastase Inhibitors Containing Conformationally Restricted Lactams As P3-P2 Dipeptide Replacements. Bioorg. Med. Chem. Lett. 1993, 3, 773-778.
28. Takahashi, S.; Radhakrishnan, R.; Rosenfield, R. E.; Meyer, E. F., Jr.; Trainor, D. A.; Stein, M. X-ray Diffraction Analysis of the Inhibition of Porcine Pancreatic Elastase by a Peptidyl Trifluoromethylketone. J. Mol. Biol. 1988, 201, 423-428.
29. Takahashi, L. H.; Radhakrishnan, R.; Rosenfield, R. E.; Meyer, E. F., Jr.; Trainor, D. A. Crystal Structure of the Covalent Complex Formed by a Peptidyl α, α-Difluoro-β-keto Amide with Porcine Pancreatic Elastase at 1. 78-Å Resolution. J. Am. Chem. Soc. 1989, 111, 3368-3374.
30. Edwards, P. D.; Meyer, E. F., Jr.; Vijayalakshmi, J.; Tuthill, P. A.; Andisik, D. A.; Gomes, B. C.; Strimpler, A. Design, Synthesis, and Kinetic Evaluation of a Unique Class of Elastase Inhibitors, the Peptidyl α-Ketobenzoxazoles, and the X-ray Crystal Structure of the Covalent Complex between Porcine Pancreatic Elastase and Ac-Ala-Pro-Val-2-Benzoxazole. J. Am. Chem. Soc. 1992, 114, 1854-1863.
31. Bode, W.; Wei, A. Z.; Huber, R.; Meyer, E.; Travis, J.; Neumann, S. X-ray Crystal Structure of the Complex of Human Leukocyte Elastase (PMN Elastase) and the Third Domain of the Turkey Ovomucoid Inhibitor. EMBO J. 1986, 5, 2453-2458.
32. Wei, A.-Z.; Mayr, I.; Bode, W. The Refined 2. 3Å Crystal Structure of Human Leukocyte Elastase in a Complex with a Valine Chloromethylketone Inhibitor. FEBS Lett. 1988, 234, 367-373.
33. Navia, M. A.; McKeever, B. M.; Springer, J. P.; Lin, T. Y.; Williams, H. R.; Fluder, E. M.; Dom, C. D.; Hoogsteen, K. Structure of Human Neutrophil Elastase in Complex with a Peptide Chloromethyl Ketone Inhibitor at 1. 84Å Resolution. Proc. Natl. Acad. Sci. U. SA. 1989, 86, 7-11.
34. Bode, W.; Meyer, E., Jr.; Powers, J. C. Human Leukocyte and Porcine Pancreatic Elastase: X-ray Crystal Structures, Mechanism, Substrate Specificity, and Mechanism-Based Inhibitors. Biochemistry 1989, 28, 1951-1963.
35. Abramovitch, R. A.; Shapiro, D. Tryptamines, Carbolines, and Related Compounds. J. Chem. Soc. 1956, 4589-4592.
36. Bernstein, P. R.; Shaw, A.; Thomas, R. M.; Warner, P.; Wolanin, D. J. European Patent Appl. No. 509, 769 A2, 1992.
37. Murakami, Y.; Tani, M.; Ariyasu, T.; Nishiyama, C.; Watanabe, T.; Yokoyama, Y. The Friedel-Crafts Acylation of Ethyl Pyrrole-2-Carboxylate. Heterocycles 1988, 27 (8), 1855-1860.
38. Edwards, P. D.; Lewis, J. J.; Perkins, C. W.; Trainor, D. A.; Wildonger, R. A. European Patent Appl., Publication No. 0 291 234 A2, 1988.
39. Williams, J. C.; Stein, R. L.; Strimpler, A. M.; Reaves, B.; Krell, R. D. Exp. Lung Res. 1991, 17, 725-741.
40. Shaw, S. K.; Dom, C. P.; Finke, P. E.; Hale, J. J.; Hagmann, 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-1. Activity of 3, 3-Diethyl-2-azetidinones. J. Med. Chem. 1992, 35, 3745.
41. Nachbar, R., Jr.; Mislow, K. QCPE Bull. 1986, 6, 96.
42. McCammon, J. A.; Harvey, S. C. Dynamics of Proteins and Nucleic Acids; Cambridge University Press: New York, 1987.
43. Brooks, C. L., III; Karplus, M.; Pettitt, B. M. Proteins: A Theoretical Perspective of Dynamics, Structure and Thermodynamics; John Wiley & Sons: New York, 1988.
44. van Gunsteren, W. F.; Weiner, P. K. Computer Simulation of Biomolecular Systems. Theoretical and Experimental Applications; Escom: Leiden, 1989.
45. Singh, U. C.; Weiner, P.; Caldwell, J. C.; Kollman, P. A. AMBER 3. 0 Revision A.; University of California: San Francisco, 1989.
46. SPARTAN 2.0; Wavefunction, Inc., 18401 Von Karman, Suite 210, Irvine, CA 92715.