Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors

Journal of Medicinal Chemistry

Volumn 42, Issue 22, 1999, Pages 4547-4562

  Almstead, Neil G ^a   Bradley, Rimma S ^a   Pikul, Stanislaw ^a   De, Biswanath ^a   Natchus, Michael G ^a   Taiwo, Yetunde O ^a   Gu, Fei ^a   Williams, Lisa E ^a   Hynd, Barbara A ^a   Janusz, Michael J ^a   Dunaway, C Michelle ^a   Mieling, Glen E ^a  

^a PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CGS 27023A; COLLAGENASE; MARIMASTAT; MATRIX METALLOPROTEINASE INHIBITOR; N HYDROXY 4 [(4 METHOXYPHENYL)SULFONYL] 2,2 DIMETHYLHEXAHYDRO 1,4 THIAZEPINECARBOXAMIDE 1,1 DIOXIDE; N HYDROXY 4 [(METHOXYPHENYL)SULFONYL] 2,2 DIMETHYLHEXAHYDRO 1,4 THIAZEPINECARBOXAMIDE; N1 [2,2 DIMETHYL 1 [(METHYLAMINO)CARBONYL]PROPYL] N4 HYDROXY 2 (2 METHYLPROPYL)BUTANEDIAMIDE; PRINOMASTAT; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; X RAY CRYSTALLOGRAPHY;

EID: 0033523954     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990330y     Document Type: Article

References (41)

1. Woessner, J. F., Jr. Matrix Metalloproteinases and Their Inhibitors in Connective Tissue Remodeling. FASEB J. 1991, 5, 2145-2154.
2. Lochter, A.; Sternlicht, M. D.; Werb, Z.; Bissell, M. J. The Significance of Matrix Metalloproteinases During Early Stages of Tumor Progression. Ann. N. Y. Acad. Sci. 1998, 857, 180-193.
3. Cawston, T. Metalloproteinase Inhibitors and the Prevention of Connective Tissue Breakdown. Pharmacol. Ther. 1996, 70, 163-182.
4. Yu, A. E.; Hewitt, R. E.; Connor, E. W.; Stetler-Stevenson, W. G. Matrix Metalloproteinases: Novel Targets for Directed Cancer Therapy. Drugs Aging 1997, 11, 229-244.
5. Chambers, A. F.; Matrisian, L. M. Changing Views of the Role of Matrix Metalloproteinases in Metastasis. J. Natl. Cancer Inst. 1997, 89, 1260-1270.
6. Brown, P. D. Matrix Metalloproteinases in Gastrointestinal Cancer. Gut 1998, 43, 161-163.
7. Bramhall, S. R. The Matrix Metalloproteinases and Their Inhibitors in Pancreatic Cancer. Int. J. Pancreat. 1997, 21, 1-12.
8. 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.
9. Yong, V. W. The Potential Use of MMP Inhibitors to Treat CNS Diseases. Exp. Opin. Invest. Drugs 1999, 8, 255-268.
10. Gijbels, K.; Galardy, R. E.; Steinman, L. Reversal of Experimental Autoimmune Encephalomyelitis with a Hydroxamate Inhibitor of Matrix Metalloproteinases. J. Clin. Invest. 1994, 94, 2177-2182.
11. Liedtke, W.; Cannella, B.; Mazzaccaro, R. J.; Clements, J. M.; Miller, K. M.; Wucherpfennig, K. W.; Gearing, A. J. H.; Raine, C, S. Effective Treatment of Models of Multiple Sclerosis by Matrix Metalloproteinase Inhibitors. Ann. Neurol. 1998, 44, 35-46.
12. Beckett, R. P.; Whittaker, M. Matrix Metalloproteinase Inhibitors 1998. Exp. Opin. Ther. Patents 1998, 8, 259-282.
13. Zask, A.; Levin, J. I.; Killar, L. M.; Skotnicki, J. S. Inhibition of Matrix Metalloproteinases: Structure Based Design. Curr. Pharm. Des. 1996, 2, 624-661.
14. White, A. D.; Bocan, T. M. A.; Boxer, P. A.; Peterson, J. T.; Schrier, D. Emerging Therapeutic Advances for the Development of Second Generation Matrix Metalloproteinase Inhibitors. Curr. Pharm. Des. 1997, 3, 45-58.
15. 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.
16. Broadhurst. M. J.; Brown, P. A.; Lawton, G.; Ballandtyne, N.; Boakakoti, N.; Bottomely, K. M. K.; Cooper, M. I.; Eatherton, A. J.; Kilford, I. R.; Malsher, P. J.; Nixon, J. S.; Lewis, E. J.; Sutton, B. M.; Johnson, W. H. Design and Synthesis of the Cartilage Protective Agent (CPA, Ro32-3555). Bioorg. Med. Chem. Lett. 1997, 7, 2299-2302.
17. 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 Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits. J. Med. Chem. 1997, 40, 2525-2532.
18. 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, 3568-3571.
19. Levin, J. I.; DiJoseph, J. F.; Killar, L. M.; Sung, A.; Walter, T.; Sharr, M. A.; Roth, C. E.; Skotnicki, J. S.; Albright, J. D. The Synthesis and Biological Activity of a Novel Series of Diazepine MMP Inhibitors. Bioorg. Med. Chem. Lett. 1998, 8, 2657-2662.
20. Zook, S. E.; Dagnino, R., Jr.; Deason, M. E.; Bender, S. L. PCT Int. Appl. WO 97/20824.
21. Mitsunobu, O. The Use of Diethyl Azodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products. Synthesis 1981, 1-28.
22. When the ester 3a was treated with aqueous hydroxide, some decomposition of the desired thiazepinecarboxylic acid was observed.
23. White, J. D.; Skeean, R. W.; Trammell, G. L. Lewis Acid and Photochemically Mediated Cyclization of Olefinic β-Keto Esters. J. Org. Chem. 1985, 50, 1939-1948.
24. Georg, G. I.; Guan, X.; Kant, J. Asymmetric Synthesis of α-Alkylated α-Amino Acid via Schmidt Rearrangement of α,α-Bisalkylated β-Keto Esters. Tetrahedron Lett. 1988, 29, 403-406.
25. Kawakami, Y.; Asai, T.; Umeyama, K.; Yamashita, Y. Selectively Deuterated and Optically Active Cyclic Ethers. J. Org. Chem. 1982, 47, 3581-3585.
26. Knight, C. G.; Willenbrock, F.; Murphy, G. A. A Novel Coumarin-labeled Peptide for Sensitive Continuous Assays of the Matrix Metalloproteinases. FEBS Lett. 1992, 296, 263-266.
27. Okada, Y.; Nagase, H.; Harris, E. D. A Metalloproteinase from Human Rheumatoid Synovial Fibroblasts that Digests Connective Tissue Matrix Components. Purification and Characterization. J. Biol. Chem. 1986, 261, 14245-14255.
28. Ohuchi, E.; Imai, K.; Fujii, Y.; Sato, H.; Seiki, M.; Okada, Y. Membrane Type 1 Matrix Metalloproteinase Digests Interstitial Collagens and other Extracellular Matrix Macromolecules. Cancer Res. 1997, 57, 2055-2060.
29. Cheng, M.; Pikul, S.; De, B.; Almstead, N. G.; Natchus, M. G. Unpublished results.
30. Compounds which possess the L-configuration were found to be at least 2 orders of magnitude less potent than the compounds from the corresponding D-series.
31. Sulphur-Containing Drugs and Related Organic Compounds: Chemistry, Biochemistry and Toxicology Vol. 1 Parts A and B, Metabolism of Sulphur Functional Groups; Damani, L. A., Ed.; Ellis Horwood Limited: London, 1989.
32. Protein Data Bank file name: 1D5J.
33. Gonella, N. C.; Li, Y.-C.; Zhang, X.; Paris, C. G. Bioactive Conformation of a Potent Stromelysin Inhibitor Determined by X-nucleus Filtered and Multidimensional NMR Spectroscopy. Bioorg. Med. Chem. 1997, 5, 2193-2201.
34. 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.; Chen, L.; Dunaway, C. M.; Gu, F.; Mieling, G. E. Design and Synthesis of Phosphinamide-Based Hydroxamic Acids as Inhibitors of Matrix Metalloproteinases. J. Med. Chem. 1999, 42, 87-94.
35. Babine, R. E.; Bender, S. L. Molecular Recognition of Protein-Ligand Complexes: Applications to Drug Design. Chem. Rev. 1997, 97, 1359-1472.
36. MT1-MMP (MMP-14) has been reported to mediate the activation of pro-gelatinase A: Sato, H.; Takino, T.; Okada, Y.; Cao, J.; Shinagawa, A.; Yamamoto, Y.; Seiki, M. A Matrix Metalloproteinase Expressed on the Surface of Invasive Tumor Cells. Nature 1994, 370, 61-65. Gelatinase A (MMP-2) is reported to be associated with tumor proliferation and metastasis in various human cancers: Stetler-Stevenson, W. G.; Aznavoorian, S.; Liotta, L. A. Tumor Cell Interactions with Extracellular Matrix During Invasion and Metastasis. Annu. Rev. Cell Biol. 1993, 9, 541-573.
37. MT1-MMP (MMP-14) has been reported to mediate the activation of pro-gelatinase A: Sato, H.; Takino, T.; Okada, Y.; Cao, J.; Shinagawa, A.; Yamamoto, Y.; Seiki, M. A Matrix Metalloproteinase Expressed on the Surface of Invasive Tumor Cells. Nature 1994, 370, 61-65. Gelatinase A (MMP-2) is reported to be associated with tumor proliferation and metastasis in various human cancers: Stetler-Stevenson, W. G.; Aznavoorian, S.; Liotta, L. A. Tumor Cell Interactions with Extracellular Matrix During Invasion and Metastasis. Annu. Rev. Cell Biol. 1993, 9, 541-573.
38. Shalinsky, D. R.; Brekken, J.; Zou, H.; McDermott, C. D.; Forsyth, P.; Edwards, D.; Margosiak, S.; Bender, S.; Truitt, G.; Wood, A.; Varki, N. M.; Appelt, K. Broad Antitumor and Antiangiogenic Activities of AG3340, a Potent and Selective MMP Inhibitor Undergoing Advanced Oncology Clinical Trials. Ann. N. Y. Acad. Sci. 1999, 878, 236-270.
39. Cremlyn, R. J.; Cronje, T.; Goulding, K. Some Phenoxybenzenesulfonyl Chlorides and Related Compounds. Aust. J. Chem. 1979, 32, 445-452.
40. Schraufstätter, E.; Schmidt-Kastner, G.; Wirth, W. Ger. Patent 1,078,129.
41. Pattenden, G.; Thom, S. M.; Jones, M. F. Enantioselective synthesis of 2-alkyl substituted cysteines. Tetrahedron 1993, 49, 2131-2138.