Matrix metalloproteinase inhibitors: A structure-activity study

Journal of Medicinal Chemistry

Volumn 41, Issue 2, 1998, Pages 199-223

  Levy, Daniel E ^a,b   Lapierre, France ^a,b   Liang, Weisheng ^a   Ye, Wenqing ^a   Lange, Christopher W ^a   Li, Xiaoyuan ^a   Grobelny, Damian ^a   Casabonne, Marie ^a   Tyrrell, David ^a   Holme, Kevin ^a,b   Nadzan, Alex ^a   Galardy, Richard E ^a  

^a Glycomed Inc   (United States)

^b 30 Invincible Court ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; COLLAGENASE; GELATINASE; HYDROXAMIC ACID; MATRIX METALLOPROTEINASE INHIBITOR; STROMELYSIN;

AMINO ACID SEQUENCE; ARTICLE; CATALYSIS; COLLAGEN METABOLISM; DISEASE ASSOCIATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SUBSTRATE; EXTRACELLULAR SPACE; HYDROGEN BOND; HYDROPHOBICITY; MULTIPLE SCLEROSIS; PSORIASIS; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COLLAGENASES; DIPEPTIDES; GELATINASES; KINETICS; MATRIX METALLOPROTEINASE 2; MATRIX METALLOPROTEINASE 3; MATRIX METALLOPROTEINASE 8; MATRIX METALLOPROTEINASE 9; METALLOENDOPEPTIDASES; MODELS, CHEMICAL; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 15444343493     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970494j     Document Type: Article

References (58)

1. Levy, D. E.; Tang, P. C.; Musser, J. H. Cell Adhesion and Carbohydrates. Annu. Rep. Med. Chem. 1994, 29, 215-224.
2. Buisson, A. C.; Gilles, C.; Polette, M.; Zahm, J. M.; Birembaut, P.; Tournier, J. M. Wound Repair-Induced Expression of Stromelysins is Associated with the Acquisition of a Mesenchymal Phenotype in Human Respiratory Epithelial Cells. Lab. Invest. 1996, 74, 658-669.
3. Lafleur, M.; Underwood, J. L.; Rappolee, D. A.; Werb, Z. Basement Membrane and Repair of Injury to Peripheral Nerve: Defining a Potential Role for Macrophages, Matrix Metalloproteinases, and Tissue Inhibitor of Metalloproteinases-1. J. Exp. Med. 1996, 184, 2311-2326.
4. Fini, M. E.; Parks, W. C.; Rinehart, W. B.; Girard, M. T.; Matsubara, M.; Cook, J. R.; Westmays, J. A.; Sadow, P. M.; Burgeson, R. E.; Jeffrey, J. J.; Raizman, M. B.; Krueger, R. R.; Zieske, J. D. Role of Matrix Metalloproteinases in Failure to Re-Epithelialize after Corneal Injury. Am. J. Path. 1996, 149, 1287-1302.
5. Buisson, A. C.; Zahm, J. M.; Polette, M.; Pierrot, D.; Bellon, G.; Puchelle, E.; Birembaut, P.; Tournier, J. M. Gelatinase B is Involved in the in vitro Wound Repair of Human Respiratory Epithelium. J. Cell. Physiol. 1996, 166, 413-426.
6. Saarialhokere, U. K.; Vaalamo, M.; Puolakkainen, P.; Airola, K.; Parks, W. C.; Karjalainenlindsberg, M. L. Enhanced Expression of Matrilysin, Collagenase, and Stromelysin-1 in Gastrointestinal Ulcers. Am. J. Path. 1996, 148, 519-526.
7. Weckroth, M.; Vaheri, A.; Lauharanta, J.; Sorsa, T.; Konttinen, Y. T. Matrix Metalloproteinases, Gelatinase and Collagenase, in Chronic Leg Ulcers. J. Invest. Dermatol. 1996, 106, 1119-1124.
8. Galardy, R. E.; Cassabonne, M. E.; Giese, C. C.; Gilbert, J. H.; LaPierre, F.; Lopez, H.; Schaefer, M. E.; Stack, R.; Sullivan, M.; Summers, B.; Tressler, R.; Tyrrell, D.; Wee, J.; Allen, S. D.; Castellot, J. J.; Barletta, J. P.; Schultz, G. X.; Fernandez, L. A.; Fisher, S.; Cui, T.-Y.; Foellmer, H. G.; Grobelny, D.; Holleran, W. M. Low Molecular Weight Inhibitors in Corneal Ulceration. Ann. N.Y. Acad. Sci. 1994, 732, 315-323.
9. Holleran, W. M.; Galardy, R. E.; Gao, W. N.; Levy, D.; Tang, P. C.; Elias, P. M. Matrix Metalloproteinase Inhibitors Reduce Phorbol Ester-Induced Cutaneous Inflammation and Hyperplasia. Arch. Dermatol. Res. 1997, 289, 138-144.
10. Hewson, A. K.; Smith, T.; Leonard, J. P.; Cuzner, M. L. Suppression of Experimental Allergic Encephalomyelitis in the Lewis Rat by the Matrix Metalloproteinase Inhibitor Ro31-9790. Inflamm. Res. 1995, 44, 345-349.
11. Maeda, A.; Sobel, R. A. Matrix Metalloproteinases in the Normal Human Central Nervous System, Microglial Nodules, and Multiple Sclerosis Lesions. J. Neuropathol. Exp. Neurol. 1996, 55, 300-309.
12. Chandler, S.; Coates, R.; Gearing, A.; Lury, J.; Wells, G.; Bone, E. Matrix Metalloproteinases Degrade Myelin Basic Protein. Neurosci. Lett. 1995, 201, 223-226.
13. Ahrens, D.; Koch, A. E.; Pope, R. M.; Steinpicarella, M.; Niedbala, M. J. Expression of Matrix Metalloproteinase 9 (96-kd Gelatinase B) in Human Rheumatoid Arthritis. Arthritis Rheumatism 1996, 39, 1576-1587.
14. Blaser, J.; Triebel, S.; Maasjosthusmann, U.; Romisch, J.; Krahlmateblowski, U.; Freudenberg, W.; Fricke, R.; Tschesche, H. Determination of Metalloproteinases, Plasminogen-Activators and their Inhibitors in the Synovial Fluids of Patients with Rheumatoid Arthritis During Chemical Synoviorthesis. Clin. Chim. Acta 1996, 244, 17-33.
15. Ohishi, K.; Fujita, N.; Morinaga, Y.; Tsuruo, T. H-31 Human Breast Cancer Cells Stimulate Type I Collagenase Production in Osteoblast-Like Cells and Induce Bone Resorption. Clin. Exp. Metastasis 1995, 13, 287-295.
16. Witty, J. P.; Foster, S. A.; Stricklin, G. P.; Matrisian, L. M.; Stern, P. H. Parathyroid Hormone-Induced Resorption in Fetal Rat Limb Bones is Associated with Production of the Metalloproteinases Collagenase and Gelatinase B. J. Bone Mineral Res. 1996, 11, 72-78.
17. Folkman, J.; Shing, Y. Angiogenesis. J. Biol. Chem. 1992, 267, 10931-10934.
18. Zucker, S.; Lysik, R. M.; Zarrabi, H. M.; Moll, U.; Tickle, S. P.; Stetter-Stevenson, W.; Baker, T. S.; Docherty, A. J. P. Plasma Assay of Matrix Metalloproteinases (MMPs) and MMP-Inhibitor Complexes in Cancer. Ann. N.Y. Acad. Sci. 1994, 732, 248-262.
19. Levy, D. E.; Ezrin, A. M. Matrix Metalloproteinase Inhibitor Drugs. Emerging Drugs: The Prospects for Improved Medicines 1997, 2, 205-230.
20. Morphy, J. R.; Millican, T. A.; Porter, J. R. Matrix Metalloproteinase Inhibitors: Current Status. Curr. Med. Chem. 1995, 2, 743-762.
21. Dhanaraj, V.; Ye, Q. Z.; Johnson, L. L.; Hupe, D. J.; Ortwine, D. F.; Dubar, J. B.; Rubin, J. R.; Pavlovsky, A.; Humblet, C.; Blundell, T. L. X-ray Structure of a Hydroxamate Inhibitor Complex of the Stromelysin Catalytic Domain and its Comparison with Members of the Zinc Metalloproteinase Superfamily. Structure 1996, 4, 375-386.
22. Grams, F.; Crimmin, M.; Hinnes, L.; Huxley, P.; Pieper, M.; Tschesche, H.; Bode W. Structure Determination and Analysis of Human Neutrophil Collagenase Complexed with a Hydroxamate Inhibitor. Biochemistry 1995, 34, 14012-14020.
23. Borkakoti, N.; Winkler, F. K.; Williams, D. H.; D'Arcy, A.; Broadhurst, M. J.; Brown, P. A.; Johnson, W. H.; Murray, E. J. Structure of the Catalytic Domain of Human Fibroblast Collagenase Complexed with an Inhibitor. Struct. Biol. 1994, 7, 106-110.
24. Stams, T.; Spurlino, J. C.; Smith, D. L.; Wahl, R. C.; Ho, T. F.; Qoronfleh, M. W.; Banks, T. M.; Rubin, B. Structure of Human Neutrophil Collagenase Reveals Large S1′ Specificity Pocket. Struct. Biol. 1994, 1, 119-123.
25. Chen, J. J.; Zhang, Y. P.; Hammond, S.; Dewdney, N.; Ho, T.; Lin, X. H.; Browner M. F.; Castelhano, A. L. Design, Synthesis, Activity, and Structure of a Novel Class of Matrix Metalloproteinase Inhibitors Containing a Heterocyclic P-2′-P-3′ Amide Bond Isostere. Bioorg. Med. Chem. Lett. 1996, 6, 1601-1606.
26. Esser, C. K.; Bugianesi, R. L.; Caldwell, C. G.; Chapman, K. T.; Durette, P. L.; Girotra N. N.; Kopka, I. E.; Lanza, T. J.; Levorse, D. A.; Maccross, M.; Owens K. A.; Ponpipom, M. M.; Simeone, J. P.; Harrison, R. K.; Niedzwiecki, L.; Becker J. W.; Marcy, A. I.; Axel, M. G.; Christen, A. J.; Mcdonnell, J.; Moore V. L.; Olszewski, J. M.; Saphos, C.; Visco, D. M.; Shen, F.; Colletti A.; Krieter, P. A.; Hagmann, W. K. Inhibition of Stromelysin-1 (MMP-3) by P-l′-Biphenylylethyl Carboxyalkyl Dipeptides. J. Med. Chem. 1997, 40, 1026-1040.
27. Tamaki, K.; Tanzawa, K.; Kurihara, S.; Oikawa, T.; Monma, S.; Shimada, K.; Sugimura Y. Synthesis and Structure-Activity Relationships of Gelatinase Inhibitors Derived from Matlystatins. Chem. Pharm. Bull. 1995, 43, 1883-1893.
28. Galardy, R. E. Galardin. Drugs Future 1993, 18, 1109-1111.
29. Compound 6a was prepared according to published procedures. (See ref 28.)
30. BOC-protected L-tryptophan, D-tryptophan, and L-phenylalanine were obtained from Aldrich or Sigma.
31. L-Abrine was obtained from Indofine Chemicals and subsequently protected with the BOC group. BOC-protected L-benzothienylalanine, L-1-naphthylalanine, L-2-naphthylalanine, L-4,4′-biphenylalanine, L-3-pyridylalanine, and L-4-pyridylalanine were obtained from Synthetech. Racemic N-methyltryptophan was obtained from Aldrich and subsequently protected with the BOC group. Resolution of BOC-N-methyltryptophan was accomplished on coupling with compound 4a. L-tert-leucine was obtained from Aldrich and subsequently protected with the BOC group.
32. BOC-L-3-quinolylalanine and BOC-L-8-quinolylalanine were prepared according to literature procedures or variations thereof. (a) Fitzi, R.; Seebach, D. Resolution and Use in α-Amino Acid Synthesis of Imidazolidinone Glycine Derivatives. Tetrahedron 1988, 44, 5277-5292. (b) Krippner, G. Y.; Harding, M. M. Intercalator Amino Acids: Synthesis of Heteroaryl Alanines. Tetrahedron: Asymmetry 1994, 5, 1793-1804. Daumas, P.; Benamar, D.; Heitz, F.; Ranjalahy-Rasoloarijao, L.; Mouden, R.; Lazaro, R.; Pullman, A. How Can the Aromatic Side-Chains Modulate the Conductance of the Gramicidin Channel? Int. J. Pept. Protein Res. 1991, 38, 218-228. Acosta, C. K.; Bahr, M. L.; Burdett, J. E., Jr.; Cessac, J. W.; Martinez, R. A.; Rao, P. N.; Kim, H. K. Synthesis of Unnatural Amino Acids. J. Chem. Res. Synop. 1991, 110-111.
33. BOC-L-3-quinolylalanine and BOC-L-8-quinolylalanine were prepared according to literature procedures or variations thereof. (a) Fitzi, R.; Seebach, D. Resolution and Use in α-Amino Acid Synthesis of Imidazolidinone Glycine Derivatives. Tetrahedron 1988, 44, 5277-5292. (b) Krippner, G. Y.; Harding, M. M. Intercalator Amino Acids: Synthesis of Heteroaryl Alanines. Tetrahedron: Asymmetry 1994, 5, 1793-1804. Daumas, P.; Benamar, D.; Heitz, F.; Ranjalahy-Rasoloarijao, L.; Mouden, R.; Lazaro, R.; Pullman, A. How Can the Aromatic Side-Chains Modulate the Conductance of the Gramicidin Channel? Int. J. Pept. Protein Res. 1991, 38, 218-228. Acosta, C. K.; Bahr, M. L.; Burdett, J. E., Jr.; Cessac, J. W.; Martinez, R. A.; Rao, P. N.; Kim, H. K. Synthesis of Unnatural Amino Acids. J. Chem. Res. Synop. 1991, 110-111.
34. BOC-L-3-quinolylalanine and BOC-L-8-quinolylalanine were prepared according to literature procedures or variations thereof. (a) Fitzi, R.; Seebach, D. Resolution and Use in α-Amino Acid Synthesis of Imidazolidinone Glycine Derivatives. Tetrahedron 1988, 44, 5277-5292. (b) Krippner, G. Y.; Harding, M. M. Intercalator Amino Acids: Synthesis of Heteroaryl Alanines. Tetrahedron: Asymmetry 1994, 5, 1793-1804. Daumas, P.; Benamar, D.; Heitz, F.; Ranjalahy-Rasoloarijao, L.; Mouden, R.; Lazaro, R.; Pullman, A. How Can the Aromatic Side-Chains Modulate the Conductance of the Gramicidin Channel? Int. J. Pept. Protein Res. 1991, 38, 218-228. Acosta, C. K.; Bahr, M. L.; Burdett, J. E., Jr.; Cessac, J. W.; Martinez, R. A.; Rao, P. N.; Kim, H. K. Synthesis of Unnatural Amino Acids. J. Chem. Res. Synop. 1991, 110-111.
35. BOC-L-3-quinolylalanine and BOC-L-8-quinolylalanine were prepared according to literature procedures or variations thereof. (a) Fitzi, R.; Seebach, D. Resolution and Use in α-Amino Acid Synthesis of Imidazolidinone Glycine Derivatives. Tetrahedron 1988, 44, 5277-5292. (b) Krippner, G. Y.; Harding, M. M. Intercalator Amino Acids: Synthesis of Heteroaryl Alanines. Tetrahedron: Asymmetry 1994, 5, 1793-1804. Daumas, P.; Benamar, D.; Heitz, F.; Ranjalahy-Rasoloarijao, L.; Mouden, R.; Lazaro, R.; Pullman, A. How Can the Aromatic Side-Chains Modulate the Conductance of the Gramicidin Channel? Int. J. Pept. Protein Res. 1991, 38, 218-228. Acosta, C. K.; Bahr, M. L.; Burdett, J. E., Jr.; Cessac, J. W.; Martinez, R. A.; Rao, P. N.; Kim, H. K. Synthesis of Unnatural Amino Acids. J. Chem. Res. Synop. 1991, 110-111.
36. Evans, D. A.; Ennis, M. D.; Mathre, D. J. Asymmetric Alkylation Reactions of Chiral Imide Enolates. A Practical Approach to the Enantioselective Synthesis of a-Substituted Carboxylic Acid Derivatives. J. Am. Chem. Soc. 1982, 104, 1737-1739.
37. Evans, D. A.; Urpi, F.; Somers, T.; Clark, J. S.; Bilodeau, M. T. New Procedures fot the Direct Generation of Titanium Enolates. Diastereoselective Bond Constructions with Representative Electrophiles. J. Am. Chem. Soc. 1990, 112, 8215-8216.
38. Dugger, R. W.; Ralbovsky, J. L.; Bryant, D.; Commander, J.; Massett, S. S.; Sage, N.; Selvidio, J. R. A Novel Synthesis of Nor-C-Statine. Tetrahedron Lett. 1992, 33, 6763-6766.
39. Norman, B. H.; Morris, M. L. A Stereospecific Synthesis of (-)-Bestaun from L-Malic Acid. Tetrahedron Lett. 1992, 33, 6803-6806.
40. Miller, A.; Beckett, R. P.; Bone, E. A.; Crimmin, M. J.; Davidson, A. H.; Davis, M. H.; Davies, S. J.; Drummond, A. H.; Galloway, W. A.; Huxley, P.; Tan, P. S.; Whittaker, M. BB-2516: An Orally Active Matrix Metalloproteinase Inhibitor. The Royal Society of Chemistry. Bioorganic Subject group. Highland Meeting in Bioorganic Chemistry. September 12-15, 1996.
41. Knight, C. G.; Willenbrock, F.; Murphy, G. Fed. Eur. Biochem. Soc. 1992, 296, 263-266.
42. Jiracek, J.; Yiotakis, A.; Vincent, B.; Checler, F.; Dive, V. Development of the First Potent and Selective Inhibitor of the Zinc Endopeptidase Neurolysin using a Systematic Approach based on Combinatorial Chemistry of Phosphinic Peptides. J. Biol. Chem. 1996, 277, 19606-19611.
43. Hughes, I.; Harper, G. P.; Karran, E. H.; Markwell, R. E.; Miles-Williams, A. J. Synthesis of Thiophenol Derivatives as Inhibitors of Human Collagenase. Bioorg. Med. Chem. Lett. 1995, 5, 3039-3042.
44. Caldwell, C. G.; Sahoo, S. P.; Polo, S. A.; Eversole, R. R.; Lanza, T. J.; Mills, S. G.; Niedzwiecki, L. M.; Izquierdomartin, M.; Chang, B. C.; Harrison, R. K.; Kuo, D. W.; Lin, T. Y.; Stein, R. L.; Durette, P. L.; Hagmann, W. K. Phosphinic Acid Inhibitors of Matrix Metalloproteinases. Bioorg. Med. Chem. Lett. 1996, 6, 323-328.
45. Chapman, K. T.; Wales, J.; Sahoo, S. P.; Niedzwiecki, L. M.; Izquierdo-Martin, M.; Chang, B. C.; Harrison, R. K.; Stein, R. L.; Hagmann, W. K. Inhibition of Matrix Metalloproteinases by PI Substituted N-Carboxyalkyl Dipeptides. Bioorg. Med. Chem. Lett. 1996, 6, 329-332.
46. Chapman, K. T.; Durette, P. L.; Caldwell, C. G.; Sperow, K. M.; Niedzwiecki, L. M.; Harrison, R. K.; Saphos, C.; Christen, A. J.; Olszewski, J. M.; Moore, V. L.; Maccoss, M.; Hagmann, W. K. Orally Active Inhibitors of Stromelysin-1 (MMP-3) Bioorg. Med. Chem. Lett. 1996, 6, 803-806.
47. Sahoo, S. P.; Caldwell, C. G.; Chapman, K. T.; Durette, P. L.; Esser, C. K.; Kopka, I. E.; Polo, S. A.; Sperow, K. M.; Niedzwiecki, L. M.; Izquierdo-Martin, M.; Chang, B. C.; Harrison, R. K.; Stein, R. L.; MacCoss, M.; Hagmann, W. K. Inhibition of Matrix Metalloproteinases by N-Carboxyalkyl Dipeptides: Enhanced Potency and Selectivity with Substituted P1′ Homophenylalanines. Bioorg. Med. Chem. Lett. 1995, 5, 2441-2446.
48. Dhanaraj, V.; Ye, Q.-Z.; Johnson, L. L.; Hupe, D. J.; Ortwine, D. F.; Dunbar, J. B., Jr.; Rubin, J. R.; Pavlovsky, A.; Humblet, C.; Blundell, T. L. X-Ray Structure of a Hydroxamate Inhibitor Complex of Stromelysin Catalytic Domain and its Comparison with Members of the Zinc Metalloproteinase Superfamily. Structure 1996, 4, 375-386.
49. 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: Three-Dimensional Structure of the Inhibited Catalytic Domain and of the C-Truncated Proenzyme. Protein Sci. 1995, 4, 1966-1976.
50. Van Doren, S. R.; Kurochkin, A. V.; Hu, W.; Ye, Q.-Z.; Johnson, L. L.; Hupe, D. J.; Zuiderweg, E. R. P. Solution Structure of the Catalytic Domain of Human Stromelysin Complexed with a Hydrophobic Inhibitor. Protein Sci. 1995, 4, 2487-2498.
51. Chander, S. K.; Antoniw, P.; Beeley, N. R. A.; Boyce, B.; Crabbe, T.; Docherty, A. J. P.; Leonard, J.; Mason, B.; Mular, K.; Millican, A. T.; Morphy, R.; Mountain, A.; O'Connell, J.; Porter, J. R.; Willmott, N. An in Vivo Model for Screening Peptidomimetic Inhibitors of Gelatinase A. J. Pharm. Sci. 1995, 84, 404-409.
52. Gowravaram, M. R.; Tomczuk, B. E.; Johnson, J. S.; Delecki, D.; Cook, E. R.; Ghose, A. K.; Mathiowetz, A. M.; Spurlino, J. C.; Rubin, B.; Smith, D. L.; Pulvino, T.; Wahl, R. C. Inhibition of Matrix Metalloproteinases by Hydroxamates Containing Heteroatom-Based Modifications of the P1′ Group. J. Med. Chem. 1995, 35, 2570-2581.
53. Foley, M. A.; Hassman, A. S.; Drewry, D. H.; Greer, D. G.; Wagner, C. D.; Feldman, P. L.; Bickett, D. M.; McGeehan, G. M.; Lambert, M. H.; Green, M. Rapid Syntheis of Novel Dipeptide Inhibitors of Human Collagenase and Gelatinase using Solid-Phase Chemistry, Bioorg. Med. Chem. Lett. 1996, 6, 1905-1910.
54. Singh, J.; Conzentino, P.; Cundy, K.; Earley, W.; Gainor, J.; Gilliam, C.; Gordon, T.; Johnson, C.; Johnson, J.; Morgan, B.; Schneider, E.; Seger, N.; Wahl, R.; Whipple, D. Relationship Between Structure and Bio-Availability in a Series of Hydroxamate Based Metalloprotease Inhibitors. Proceedings of the 13th American Peptide Symposium, Edmonton, Canada, 1988, pp 864-866.
55. Castelhano, A. L.; Billedeau, R.; Dewdney, N.; Donnelly, S.; Horne, S.; Kurz, L. J.; Liak, T. J.; Martin, R.; Uppington, R.; Yuan, Z.; Krantz, A. Novel Indolactam-Based Inhibitors of Matrix Metalloproteinases. Bioorg. Med. Chem. Lett. 1995, 5, 1415-1420.
56. Monocarboxybenzyloxy ethylenediamine was prepared according to published procedures. Lawson, W. B.; Leafer, M. D., Jr.; Tewes, A.; Rao, G. J. S. Alkylation of Serine at the Active Site of Trypsin. Z. Physiol. Chem. 1968, 349, 251-262.
57. 2-Aminomethylthiazole was prepared according to published procedures. Irako, N.; Hamada, Y.; Shioiri, T. A New Asymmetric Synthesis of (S)-Dolaphenine and its Heteroaromatic Congeners Utilizing (+)-3-Hydroxy-2-Caranone as Chiral Auxiliaries. Tetrahedron 1995, 51, 12731-12744.
58. Levy, D. E.; Tang, P. C.; Sweet, K.; Summers, B.; LaPierre, F.; Ezrin, A M. A Hydroxamic Acid Matrix Metalloprotease Inhibitor Blocks the Activity of Endothelin Converting Enzyme in Anesthetized Rats. Med. Chem. Res. 1994, 4, 547-553.