Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors

Journal of Medicinal Chemistry

Volumn 42, Issue 9, 1999, Pages 1525-1536

  Jacobsen, E Jon ^a   Mitchell, Mark A ^a   Hendges, Susan K ^a   Belonga, Kenneth L ^a   Skaletzky, Louis L ^a   Stelzer, Lindsay S ^a   Lindberg, Thomas J ^a   Fritzen, Edward L ^a   Schostarez, Heinrich J ^a   O'Sullivan, Theresa J ^a   Maggiora, Linda L ^a   Stuchly, Christopher W ^a   Laborde, Alice L ^a   Kubicek, Marc F ^a   Poorman, Roger A ^a   Beck, Joan M ^a   Miller, Henry R ^a   Petzold, Gary L ^a   Scott, Pam S ^a   Truesdell, Scott E ^a   Wallace, Tanya L ^a   Wilks, John W ^a   Fisher, Christopher ^a   Goodman, Linda V ^a   Kaytes, Paul S ^a   Ledbetter, Stephen R ^a   Powers, Elaine A ^a   Vogeli, Gabriel ^a   Mott, John E ^a   Trepod, Catherine M ^a   Staples, Douglas J ^a   Baldwin, Eric T ^a   Finzel, Barry C ^a   more..

^a Chemical Process Research and Development   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GELATINASE; MATRIX METALLOPROTEINASE INHIBITOR; STROMELYSIN; THIADIAZOLE DERIVATIVE; UREA DERIVATIVE;

ARTICLE; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; HYDROGEN BOND; STRUCTURE ACTIVITY RELATION; TISSUE REPAIR;

BINDING SITES; FLUORESCENCE; HUMANS; MATRIX METALLOPROTEINASE 3; MODELS, MOLECULAR; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THIADIAZOLES; UREA;

EID: 0033529047     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9803222     Document Type: Article

References (42)

1. Docherty, A. J. P.; Murphy, G. The tissue metalloproteinase family and the inhibitor TIMP: A study using cDNAs and recombinant proteins. Ann. Rheum. Dis. 1990, 49, 469-479.
2. (a) Cawston, T. E.; Murphy, G.; Mercer, E.; Galloway, W. A.; Hazelman, B. L.; Reynolds, J. J. The interaction of purified rabbit bone collagenase with purified rabbit bone metalloproteinase inhibitor. Biochem. J. 1983, 211, 313-318.
3. (b) Stelter-Stephenson, W. G.; Krutzsch, H. C.; Liotta, L. A. Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J. Biol. Chem. 1889, 264, 17374-17378.
4. Henderson, B.; Docherty, A. J. P.; Beeley, N. R. A. Design of inhibitors of articular cartilage destruction. Drugs Future 1990, 15, 495-508.
5. (a) Birkedal-Hansen, H. From tadpole collagenase to a family of matrix metalloproteinases. J. Oral Pathol. 1988, 17, 445-451
6. (b) Emonard, H.; Grimaud, H. Matrix metalloproteinases. A review. Cell. Mol. Biol. 1990, 36, 131-153.
7. (c) Matrisian, L. M. The matrix-degrading metalloproteinases. BioEssays 1992, 14, 455-463.
8. (d) Murphy, G. J. P.; Murphy, G.; Reynolds, J. J. The origin of matrix metalloproteinases and their familial relationships. FEBS Lett. 1991, 289, 4-7.
9. (a) Walakovits, L. A.; Moore, V. L.; Bhardwaj, N.; Gallick, G. S.; Lark, M. W. Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and post-traumatic knee injury. Arthr. Rheum. 1992, 35, 35-42.
10. (b) Okada, Y.; Shinmei, M.; Tanaka, O.; Naka, K.; Kimura, A.; Nakanishi, I.; Bayliss, M. T.; Iwata, K.; Nagase, H. Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. Lab. Invest. 1992, 66, 680-690.
11. McCachren, S. S.; Haynes, B. F.; Niedel, J. E. Localization of collagenase mRNA in rheumatoid arthritis synovium by in situ hybridization histochemistry. J. Clin. Immunol. 1990, 10, 19-27.
12. Engle, G.; Heselmeyer, K.; Auer, G.; Backdahl, M.; Eriksson, E.; Linder, S. Correlation between stromelysin-3 mRNA level and outcome of human breast cancer. Int. J. Cancer 1994, 58, 830-835.
13. Zeng, Z. S.; Haung, Y.; Cohen, A. M.; Guillem, J. G. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J. Clin. Oncol. 1996, 14, 3133-3140.
14. Overall, C. M.; Wiebkin, O. W.; Thonard, J. C. Demonstration of tissue collagenase activity in vivo and its relationship to inflammation severity in human gingiva. J. Periodontal Res. 1987, 22, 81-88.
15. Henney, A. M.; Wakeley, P. R.; Davies, M. J.; Foster, K.; Hembry, R.; Murphy, G.; Humphries, S. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 8154-8158.
16. Vine, N.; Powell, J. T. Metalloproteinases in degenerative aortic diseases. Clin. Sci. 1991, 81, 233-239.
17. Gearing, A. J. H.; Beckett, P.; Christodoulou, M.; Churchill, M.; Clements, J.; Davidson, A. H.; Drummond, A. H.; Galloway, W. A.; Gilbert, R.; Gordon, J. L.; Leber, T. M.; Mangan, M.; Miller, K.; Nayee, P.; Owen, K.; Patel, S.; Thomas, W.; Wells, G.; Wood, L. M.; Woolley, K. Processing of tumor necrosis factor-α precursor by metalloproteinases. Nature 1994, 370, 555-557.
18. 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.; Kronheim, S. R.; Petersen, M.; Gerhart, M.; Kozlosky, C. J.; March, C. J.; Black, R. A. Protection against a lethal dose of endotoxin by an inhibitor of tumor necrosis factor processing. Nature 1994, 370, 218-220.
19. Vilcek, J.; Lee, T. H. Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions. J. Biol. Chem. 1991, 266, 7313-7316.
20. Schwartz, M. A.; VanWart, H. E. Synthetic inhibitors of bacterial and mammalian interstitial collagenases. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier Science Publishers B.V.: The Netherlands, 1992; Vol. 9.
21. For recent reviews see: (a) Porter, J. R.; Millican, T. A.; Morphy, J. R. Recent developments in matrix metalloproteinase inhibitors. Exp. Opin. Ther. Patents 1995, 5, 1287-1296.
22. (b) Brown, P. D. Matrix metalloproteinase inhibitors: A new class of anticancer agent. Curr. Opin. Invest. Drugs 1993, 2, 617-626.
23. Beckett, R. P.; Davidson, A. H.; Drummond, A. H.; Huxley, P.; Whittaker, M. Recent advances in matrix metalloproteinase inhibitor research. Drug Discovery Today 1996, 1, 16-26.
24. Moderate to low bioavailability, depending on species, has been reported for BB-2516; see: Drummond, A. H.; Beckett, P.; Bone, E. A.; Brown, P. D.; Davis, M.; Galloway, W. A. BB-2516: An orally bioavailable matrix metalloproteinase inhibitor with efficacy in animal cancer models. 86th Annual Meeting of the American Association for Cancer Research, Toronto, Ontario, Canada, Mar 18-22, 1995.
25. Oleksyszyn, J.; Jacobsen, A. R. U.S. Patent 5,677282, Oct 14, 1997.
26. Schostarez, H. J.; Treiberg, J. A.; O'Sullivan, T. J.; Stockman, B. J.; Scahill, T. A.; Walden, D. J.; Magoria, L. L.; Lindberg, T. J.; Mitchell, M. A.; Harper, D. E.; Warpehoski, M. A.; Laborde, A.; Miller, H. R.; Stuchley, C. W. 5-Acylamino-1,3,4-thiadiazole-2-thiones: Synthesis and enzyme-inhibitor NMR spectroscopic studies of a novel class of zinc chelating matrix metalloproteinase (MMP) inhibitors. Unpublished results.
27. Gooley, P. R.; O'Connell, J. F.; Marcy, A. I.; Cuca, G. C.; Salowe, S. P.; Bush, B. L.; Hermes, J. F.; Esser, C. K.; Hagmann, W. K.; Springer, J. P.; Johnson, B. A. The NMR structure of the inhibited catalytic domain of human stromelysin-1. Nature Struct. Biol. 1994, 1, 111-118.
28. Becker, J. W.; Marcy, A. I.; Rokosz, L. L.; Axel, M. G.; Burbaum, J. J.; Fitzgerald, P. M. D.; Cameron, P. M.; Esser, C. K.; Hagmann, W. K.; Hermes, J. D.; Springer, J. P. Stromelysin-1: The three-dimensional structure of the inhibited catalytic domain and the C-truncated proenzyme. Protein Sci. 1995, 4, 1966-1976.
29. For reviews see: Kornis, G. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Ed.; Pergamon Press: Oxford, England, 1984; Vol. VI, p 545.
30. Ninomiya, K.; Shioiri, T.; Yamada, S. Phosphorus in organic synthesis-VII. Diphenyl phosphorazidate (DPPA). A new convenient reagent for a modified Curtius reaction. Tetrahedron 1974, 30, 2151-2157.
31. Jensen, K. A.; Anthoni, U.; Kagi, B.; Larsen, C.; Pedersen, C. T. Studies of thio acids and their derivatives. Acta Chem. Scand. 1968, 22, 1-50.
32. Nowick, J. S.; Powell, N. A.; Nguyen, T. M.; Noronha, G. An improved method for the synthesis of enatiomerically pure amino acid ester isocyanates. J. Org. Chem. 1992, 57, 7364-7366.
33. Manetta, J. V.; Lai, M.-H. T.; Osborne, H. E.; Dee, A.; Margolin, N.; Sportsman, J. R.; Vlahos, C. J.; Yan, S. B.; Heath, W. F. Design and implementation of a particle concentration fluorescence method for the detection of HIV-1 protease inhibitors. Anal. Biochem. 1992, 202, 10-15.
34. Moss, M. L.; Jin, S.-L. C.; Milla, M. E.; Burkhart, W.; Carter, H. L.; Chen, W.-J.; Clay, W. C.; Didsbury, J. R.; Hassler, D.; Hoffman, C. R.; Kost, T. A.; Lambert, M. H.; Leesnitzer, M. A.; McCauley, P.; McGeehan, G.; Mitchell, J.; Moyer, M.; Pahel, G.; Rocque, W.; Overton, L. K.; Schoenen, F.; Seaton, T.; Su, J.-L.; Warner, J.; Willard, D.; Becherer, J. D. Cloning of a disintegrin metalloproteinase that processes precursor tumor-necrosis factor-α. Nature 1997, 385, 733-736.
35. 14-16 when this work began. The potent effects of ester 51 against stromelysin were completely unexpected.
36. Stockman, B. J.; Waldon, D. J.; Gates, J. A.; Scahill, T. A.; Kloosterman, D. A.; Mizsak, S. A.; Jacobsen, E. J.; Belonga, K. L.; Mitchell, M. A.; Mao, B.; Petke, J. D.; Goodman, L.; Powers, E. A.; Ledbetter, S. R.; Kaytes, P. S.; Vogeli, G.; Marshall, V. P.; Petzold, G. L.; Poorman, R. A Solution structures of stromelysin complexed to thiadiazole inhibitors. Protein Sci. 1998, 7, 2281-2286.
37. Finzel, B. C.; Baldwin, E. T.; Bryant, G. L., Jr.; Hess, G. F.; Wilks, J. W.; Trepod, C. M.; Mott, J. E.; Marshall, V. P.; Petzold, G. L.; Poorman, R. A.; O'Sullivan, T. J.; Schostarez, H. J.; Mitchell, M. A. Structural characterization of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity. Protein Sci. 1998, 7, 2118-2126.
38. 2) to give the desired product.
39. (a) Saus, J.; Quinones, S.; Otani, Y.; Nagase, H.; Harris, E. D., Jr.; Kurkinen, M. The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin. J. Biol. Chem. 1988, 263, 6742-6745.
40. (b) Marcy, A. I.; Eiberger, L. L.; Harrison, R.; Chan, H. K.; Hutchinson, N. I.; Hagmann, W. K.; Cameron, P. M.; Boulton, D. A.; Hermes, J. D. Human fibroblast stromelysin catalytic domain: expression, purification, and characterization of a C-terminally truncated form. Biochemistry 1991, 30, 6476-6483.
41. Jentoft, N.; Dearborn, D. G. Labeling of proteins by reductive methylation using sodium cyanoborohydride. J. Biol. Chem. 1979, 254, 4359-4365.
42. 4-NH-biotin.