Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I

Journal of Medicinal Chemistry

Volumn 40, Issue 23, 1997, Pages 3820-3828

  Chatterjee, Sankar ^a   Ator, Mark A ^a   Bozyczko Coyne, Donna ^a   Josef, Kurt ^a   Wells, Gregory ^a   Tripathy, Rabindranath ^a   Iqbal, Mohamed ^a   Bihovsky, Ron ^a   Senadhi, Shobha E ^a   Mallya, Satish ^a   O'Kane, Teresa M ^a   McKenna, Beth Ann ^a   Siman, Robert ^a   Mallamo, John P ^a  

^a CEPHALON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALPAIN I; CALPASTATIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CELL KILLING; CELL SURVIVAL; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; FLUORINATION; NERVE DEGENERATION; NONHUMAN; STROKE;

CALPAIN; CATHEPSIN B; CATHEPSINS; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; DIPEPTIDES; ENDOPEPTIDASES; HUMANS; HYDROCARBONS, FLUORINATED; KETONES; LEUKEMIA, T-CELL; RECOMBINANT PROTEINS; TUMOR CELLS, CULTURED;

EID: 9844229891     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970197e     Document Type: Article

References (33)

1. Barinaga, M. Finding New Drugs to Treat Stroke. Science 1996, 272, 664-666.
2. Brennan, M. B. Stroke Drugs Send Researchers Back to the Drawing Board. Chem. Eng. News 1996, May 13, 41-45.
3. Koroshetz, W. J.; Moskowitz, M. A. Emerging Treatments for Stroke in Humans. Trends Pharmacol. Sei. 1996,17, 227-233.
4. (a) 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. E.; 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, 7,539-544.
5. (b) Mehdi, S. Cell-Penetrating Inhibitors of Calpain. Trends Biol. Sei. 1991, 16, 150-153.
6. Harbeson, S. L.; Abelleira, S. M.; Akiyama, A.; Barrett, R., Ill; Carroll, R. M.; Straub, J. A.; Tkacz, J. N.; Wu, C.; Musso, G. F. Stereospecific Synthesis of Peptidyl α-Keto Amides as Inhibitors of Calpain. J. Med. Chem. 1994,37,2918-2929.
7. Li, Z.; Patil, G.; Golubski, Z. E.; Hori, H.; Tehrani, K.; Foreman, J. E.; Eveleth, D. D.; Bartus, R. T.; Powers, J. C. Peptide α-Keto Ester, α-Keto Amide, and α-Keto Acid Inhibitors of Calpains and Other Cysteine Proteases. J. Med. Chem. 1993, 36, 3472-3480.
8. (e) Li, Z.; Ortega-Vilain, A.; Patil, G. S.; Chu, D.; Foreman, J. E.; Eveleth, D. D.; Powers, J. C. Novel Peptidyl α-Keto Amide Inhibitors of Calpains and Other Cysteine Proteases. J. Med. Chem. 1996, 39, 4089-4098.
9. (a) Crawford, C.; Mason, R. W.; Wickstrom, P.; Shaw, E. The Design of Peptidyldiazomethane Inhibitors to Distinguish between the Cysteine Proteinases Calpain II, Cathepsin L, and Cathepsin B. Biochem. J. 1988, 253, 751-758.
10. (b) McGowan, E. B.; Becker, E.; Detwiler, T. C. Inhibition of Calpain in Intact Platelets by the Thiol Protease Inhibitor E-64d. Biochem. Biophys. Res. Commun. 1989, 158, 432-435.
11. Huang, Z.; McGowan, E. B.; Detwiler, T. C. Ester and Amide Derivatives of E64c as Inhibitors of Platelet Calpains. J. Med. Chem. 1992, 35, 2048-2054.
12. Harris, A. L.; Gregory, J. S.; Maycock, A. L.; Graybill, T. L.; Osifo, I. K.; Schmidt, S. L.; Dolle, R. E. Characterization of a Continuous Fluorogenic Assay for Calpain I. Kinetic Evaluation of Peptide Aldehydes, Halomethyl Ketones and (Acyloxy)Methyl Ketones as Inhibitors of the Enzyme. Bioorg. Med. Chem. Lett. 1995, 5, 393-398.
13. Angliker, H.; Anagli, J.; Shaw, E. Inactivation of Calpain by Peptidyl Fluoromethyl Ketones. J. Med. Chem. 1992, 35, 216-220.
14. Chatterjee, S.; Josef, K; Wells, G.; Iqbal, M.; Bihovsky, R.; Mallamo, J. P.; Ator, M. A.; Bozyczko-Coyne, D.; Mallya, S.; Senadhi, S.; Siman, S. Potent Fluoromethyl Ketone Inhibitors of Recombinant Human Calpain I. Bioorg. Med. Chem. Lett. 1996, 6, 1237-1240.
15. 2F to be an inhibitor of chicken gizzard calpain II; see ref 6.
16. (b) Peptidyl fluoromethyl ketones were first reported in the literature by Rasnick; see: Rasnick, D. Synthesis of Peptide Fluoromethyl Ketones and the Inhibition of Human Cathepsin B. Anal. Biochem. 1985, 149, 461-465.
17. Wegler, R.; Bodenbenner, K. N,N-Dialkylamidosulfonyl Chlorides. Ann. Chem. 1959, 624, 25-29.
18. Majer, P.; Randad, R. S. A Safe and Efficient Method for Preparation of N,N′-Unsymmetrically Disubstituted Ureas Utilizing Triphosgene. J. Org. Chem. 1994, 59, 1937-1938.
19. Imperialo, B.; Abeles, R. H. A Versatile Synthesis of Peptidyl Fluoromethyl Ketones. Tetrahedron Lett. 1986, 27, 135-138.
20. Revesz, L.; Briswalter, C.; Heng, R.; Leutwiler, A.; Mueller, R.; Wuethrich, H-J. Synthesis of PI Aspartate-Based Peptide Acyloxymethyl and Fluoromethyl Ketones as Inhibitors of Interleukin-1β-Converting Enzyme. Tetrahedron Lett. 1994, 35, 9693-9696.
21. Lai, G. S. Site-Selective Fluorination of Organic Compounds Using 1-Alkyl-4-fluoro-1,4-diazabicyclo(2,2,2)octane Salts (Selectflur Reagents). J. Org. Chem. 1993, 58, 2791-2796.
22. Meyer, S. L.; Bozyczko-Coyne, D.; Mallya, S. K.; Spais, C. M.; Bihovsky, R.; Kawooya, J. K.; Lang, D. M.; Scott, R. W; Siman, R. Biologically-Active Monomeric and Heterodimeric Recombinant Human Calpain I Produced Using the Baculovirus Expression System. Biochem. J. 1996, 314, 511-519.
23. 7 "the discrepancy may arise due to methodological differences in the analysis of progress curves at multiple inhibitor concentrations employed in this study and the preincubation experiments performed at a single inhibitor concentration by Shaw et al." One of the reviewers, however, commenting on the greater reactvity of the THP-protected serine fluoromethyl ketone than of the corresponding unprotected serine analog, stated that "It seems that these differences could be explained by the large differences in the structure of the two compounds without considering the contribution of the serine hydroxyl group."
24. Pliura, D. H.; Bonaventura, B. J.; Smith, R. A.; Coles, P. J.; Krantz, A. Comparative Behaviour of Calpain and Cathepsin B toward Peptidyl Acyloxymethyl Ketones, Sulphonium Methyl Ketones and other Potential Inhibitors of Cysteine Proteinases. Biochem. J. 1992, 288, 759-762.
25. Parkes, C.; Kembhavi, A. A.; Barrett, A. J. Calpain Inhibition by Peptide Epoxides. Biochem. J. 1985, 230, 509-516.
26. Baki, A.; Tompa, P.; Alexa, A.; Molnar, O.; Friedrich, P. Autolysis Parallels Activation of mu-Calpain. Biochem. J. 1996,318,897-901.
27. Mehdi, S.; Angejastro, M. R.; Wiseman, J. S.; Bey, P. Inhibition of the Proteolysis of Rat Erythrocyte Membrane Proteins by a Synthetic Inhibitor of Calpain. Biochem. Biophys. Res. Commun. 1988,157, 1117-1123.
28. (a) Thomberry, N. A.; Peterson, E. P.; Zhao, J. J.; Howard, A. D.; Griffin, P. R.; Chapman, K. T. Inactivation of Interleukin-1β Converting Enzyme by Peptide (Acyloxy)methyl Ketones. Biochemistry 1994, 33, 3934-3940.
29. (b) 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, 4678-4687.
30. Laemmli, U. K. Cleavage of Structural Proteins During the Assembly of the Head of Bacteriophage T4. Nature 1970, 227, 680-685.
31. Towbin, H.; Staehelin, T.; Gordon, J. Electrophoretic Transfer of Proteins from Polyacrylamide Gels to Nitrocellulose Sheets: Procedure and Some Applications. Proc. Natl. Acad. Sei. U.SA. 1979, 76, 4350-4354.
32. Mason, R. W.; Green, G. D. J.; Barrett, A. J. Human Liver Cathepsin L. Biochem. J. 1985, 226, 233-241.
33. Roberts-Lewis, J. M.; Savage, M. J.; Marcy, V. R.; Pinsker, L. R.; Siman, R. Immunolocalization of Calpain I-mediated Spectrin Degradation to Vulnerable Neurons in the Ischemic Gerbil Brain. J. Neurosci. 1994,14 (6), 3934-3944.