Azetidine-2,4-diones (4-oxo-β-lactams) as scaffolds for designing elastase inhibitors

Journal of Medicinal Chemistry

Volumn 51, Issue 6, 2008, Pages 1783-1790

  Mulchande, Jalmira ^a   Guedes, Rita C ^a   Tsang, Wing Yin ^b   Page, Michael I ^b   Moreira, Rui ^a   Iley, Jim ^c  

^a UNIVERSITY OF LISBON   (Portugal)

^b UNIVERSITY OF HUDDERSFIELD   (United Kingdom)

^c OPEN UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 CHLOROPHENYL) 3,3 DIETHYLAZETIDINE 2,4 DIONE; 1 (4 CHLOROPHENYL) 3,3 DIMETHYLAZETIDINE 2,4 DIONE; 1 BENZYL 3,3 DIETHYLAZETIDINE 2,4 DIONE; 1 BENZYL 3,3 DIMETHYLAZETIDINE 2,4 DIONE; 3,3 DIETHYL 1 (4 METHOXYPHENYL)AZETIDINE 2,4 DIONE; 3,3 DIETHYL 1 (4 TOLYL)AZETIDINE 2,4 DIONE; 3,3 DIETHYL 1 PHENYLAZETIDINE 2,4 DIONE; 4 (3,3 DIETHYL 2,4 DIOXOAZETIDINE 1 YL)BENZONITRILE; AZETIDINE DERIVATIVE; BETA LACTAM DERIVATIVE; ELASTASE INHIBITOR; ETHYL 2 (3,3 DIETHYL 2,4 DIOXOAZETIDIN 1 YL)ACETATE; LEUKOCYTE ELASTASE; PANCREATIC ELASTASE; UNCLASSIFIED DRUG;

ARTICLE; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; DRUG DESIGN; DRUG INHIBITION; DRUG SYNTHESIS; ENZYME ACTIVITY; HUMAN; HYDROLYSIS; NONHUMAN; STEADY STATE; STRUCTURE ACTIVITY RELATION;

ANIMALS; AZETIDINES; BINDING SITES; DRUG DESIGN; ENZYME INHIBITORS; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PANCREATIC ELASTASE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SWINE;

EID: 41149169679     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701257h     Document Type: Article

References (36)

1. Barnes, P. J. Chronic obstructive pulmonary disease. New Engl. J. Med. 2000, 343, 269-280.
2. Cowan, K. N.; Heilbut, A; Humpl, T.; Lam, C.; Ito, S.; Rabinovitsch, M. Complete reversal of pulmonary hypertension in rats by a serine elastase inhibitor. Nat. Med. 2005, 6, 698-702.
3. Ohbayashi, H. Current synthetic inhibitors of human neutrophil elastase in 2005. Expert Opin. Ther. Pat. 2005, 15, 759-771.
4. Donnelly, L. E.; Rogers, D. F. Therapy for chronic obstructive pulmonary disease in the 21st century. Drugs 2003, 63, 1973-1998.
5. Malhotra, S.; Man, S. F. P.; Sin, D. D. Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin. Emerging Drugs 2006, 11, 275-291.
6. Konaklieva, M. I. β-Lactams as inhibitors of serine enzymes. Curr. Med. Chem 2002, 1, 215-238.
7. Powers, J. C.; Asgian, J. L.; Ekicu, Ö. D.; James, K. E. Irreversible inhibitors of serine, cysteine, and threonine proteases. Chem. Rev. 2002, 102, 4639-4750.
8. Konaklieva, M. I.; Plotkin, B. J. The relationship between inhibitors of eukaryotic and prokaryotic serine proteases. Mini-Rev. Med. Chem. 2004, 4, 721-739.
9. Leung, D.; Abbenante, G.; Fairlie, D. P. Protease inhibitors: Current status and future prospects. J. Med. Chem. 2000, 43, 305-341.
10. Moreira, R.; Santana, A. B.; Iley, J.; Neres, J.; Douglas, K. T.; Horton, P. N.; Hursthouse, M. B. Design, synthesis and enzymatic evaluation of N1-acyloxyalkyl- and N1-oxazolidin-2,4-dion-5-yl-substituted β-lactams as novel inhibitors of human leukocyte elastase. J. Med. Chem. 2005, 48, 4861-4870.
11. Tsang, W. Y.; Ahmed, N.; Hardling, L.; Hemming, K.; Laws, A. P.; Page, M. Acylation versus sulfonylation in the inhibition of elastase by 3-oxo-β-sultams. J. Am. Chem. Soc. 2005, 127, 8946-8947.
12. Ahmed, N.; Tsang, W. Y.; Page, M. I. Acyl vs sulfonyl transfer in N-acyl β-sultams and 3-oxo-β-sultams. Org. Lett. 2004, 6, 201-203.
13. Page, M. I. The mechanisms of reactions of β-lactams antibiotics. Adv. Phys. Org. Chem. 1987, 23, 165-270.
14. Sykes, N. O.; Macdonald, S. J. F.; Page, M. I. Acylating agents as enzyme inhibitors and understanding their reactivity for drug design. J. Med. Chem. 2002, 45, 2850-2856.
15. Morrison, J.; Walsh, C. The behaviour and significance of slow binding enzyme inhibitors. Adv. Enzym. 1988, 61, 201-299.
16. Stein, R. L.; Strimpler, A. M.; Viscarello, B. R.; Wildonger, R. A.; Mauger, R. C.; Traino, D. A. Mechanism for slow-binding inhibition of human leukocyte elastase by valine-derived benzoxazinones. Biochemistry 1987, 26, 4126-4130.
17. Kuzmic, P. Program DYNAFIT for the analysis of enzyme kinetic data: Application to HIV proteinase. Anal. Biochem. 1996, 237, 260-273.
18. King, J. F. In The Chemistry of Sulphonic Acids, Esters and their Derivatives; Patai, S., Rappoport, Z., Eds.; John Wiley: Chichester, U.K., 1991; pp. 249-259..
19. Page, M. I. β-Sultams - Mechanism of reactions and use as inhibitors of serine proteases. Acc. Chem. Res. 2004, 37, 297-303.
20. Indelicato, J. M.; Pasini, C. E. The acylating potential of γ-lactam antibacterials: Base hydrolysis of bicyclic pyrazolidinones. J. Med. Chem. 1988, 31, 1227-1230.
21. Krantz, A.; Spencer, R. W.; Tam, T. F.; Liak, T. J.; Copp, L. J.; Thomas, E. M.; Rafferty, S. P. Design and synthesis of 4H-3,1-benzoxazin-4-ones as potent alternate substrate inhibitors of human leukocyte elastase. J. Med. Chem. 1990, 33, 464-479.
22. Knight, W.; Green, B.; Chabin, R.; Gale, P.; Maycock, A.; Weston, H.; Kuo, D.; Westler, W.; Dorn, C.; Finke, P.; Hagmann, W.; Hale, J.; Liesch, J.; MacCoss, M.; Navia, M.; Shah, S.; Underwood, D.; Doherty, J. Specificity, stability, and potency of monocyclic β-lactam inhibitors of human leucocyte elastase. Biochemistry 1992, 31, 8160-8170.
23. Golik, U. The synthesis of malonimide derivatives as potential penicillin analogs. J. Heterocycl. Chem. 1972, 9, 21-24.
24. Dai, S. A.; Juang, T. Y.; Chen, C. P.; Chang, H. Y.; Kuo, W. J.; Su, W. C.; Jeng, R. J. Synthesis of N-aryl azetidine-2,4-diones and polymalonamides prepared from selective ring-opening reactions. J. Appl. Polym. Sci. 2007, 103, 3591-3599.
25. Hagmann, W. K.; Kissinger, A. L.; Shah, S. K.; Finke, P. E.; Dorn, C. P.; Brause, K. A.; Ashe, B. M.; Weston, H.; Maycock, A. L.; Knight, W. B.; Dellea, P. S.; Fletcher, D. S.; Hand, K. M.; Osinga, D.; Davies, P.; Doherty, J. B. Orally active β-lactam inhibitors of human-leukocyte elastase.2. Effect of C-4 substitution. J. Med. Chem. 1993, 36, 771-777.
26. Kitz, R.; Wilson, I. B. Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J. Biol. Chem. 1962, 12, 2940-2945.
27. Parr, R. G.; Yang, W. Density Functional Theory of Atoms and Molecules; Oxford University Press: Oxford, U. K., 1989.
28. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
29. (b) Lee, C. T.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-789.
30. Frisch, M. J. Gaussian 03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
31. Wang, J.; Wang, W.; Kollman, P. A.; Case, D. A. Automatic atom type and bond type perception in molecular mechanical calculations. J. Mol. Graph. Model. 2006, 25, 247.
32. For the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of CA, San Francisco (supported by NIH P41 RR-01081), see: Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera - A visualization system for exploratory research and analysis. J. Comput. Chem. 2004, 25, 1605-1612.
33. Wilmouth, R. C.; Westwood, N. J.; Anderson, K.; Brownlee, W.; Claridge, T. D. W.; Clifton, I. J.; Pritchard, G. J.; Aplin, R. T.; Schofield, C. J. Inhibition of elastase by N-sulfonylaryl β-lactams: Anatomy of a stable acyl-enzyme complex. Biochemistry 1998, 37, 17506-17513.
34. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M., Jr.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197.
35. CCDC Software Ltd., Cambridge, U.K.
36. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.