Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors

Journal of Medicinal Chemistry

Volumn 48, Issue 22, 2005, Pages 6767-6771

  Ghosh, Arun K ^a,b   Xi, Kai ^a,b   Ratia, Kiira ^b   Santarsiero, Bernard D ^b   Fu, Wentao ^b   Harcourt, Brian H ^d   Rota, Paul A ^d   Baker, Susan C ^c   Johnson, Michael E ^b   Mesecar, Andrew D ^b  

^a PURDUE UNIVERSITY   (United States)

^b UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^c LOYOLA UNIVERSITY CHICAGO   (United States)

^d CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHLOROMETHYL KETONE; PROTEINASE INHIBITOR; RUPINTRIVIR; SEVERE ACUTE RESPIRATORY SYNDROME CHYMOTRYPSIN LIKE PROTEASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG DESIGN; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROGEN BOND; SARS CORONAVIRUS;

ANIMALS; ANTIVIRAL AGENTS; CELLS, CULTURED; CHYMASES; CRYSTALLOGRAPHY, X-RAY; DIPEPTIDES; DRUG DESIGN; HUMANS; ISOXAZOLES; KINETICS; LACTAMS; MODELS, MOLECULAR; MOLECULAR MIMICRY; PEPTIDES; SARS VIRUS; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 27444437908     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050548m     Document Type: Article

References (20)

1. (a) Drosten, C.; Gunther, S.; Preiser, W.; van der Werf, S.; Brodt, H. R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R. A.; Berger, A.; Burguiere, A. M.; Cinatl, J.; Eickmann, M.; Escriou, N.; Grywna, K.; Kramme, S.; Manuguerra, J. C.; Muller, S.; Rickerts, V.; Sturmer, M.; Vieth, S.; Klenk, H. D.; Osterhaus, A. D.; Schmitz, H.; Doerr, H. W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348, 1967-1976.
2. (b) Ksiazek, T. G.; Erdman, D.; Goldsmith, C. S.; Zaki, S. R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J. A.; Lim, W.; Rollin, P. E.; Dowell, S. F.; Ling, A. E.; Humphrey, C. D.; Shieh, W. J.; Guarner, J.; Paddock, C. D.; Rota, P.; Fields, B.; DeRisi, J.; Yang, J. Y.; Cox, N.; Hughes, J. M.; LeDuc, J. W.; Bellini, W. J.; Anderson, L. J. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348, 1953-1966.
3. Peiris, J. S.; Lai, S. T.; Poon, L. L.; Guan, Y.; Yam, L. Y.; Lim, W.; Nicholls, J.; Yee, W. K.; Yan, W. W.; Cheung, M. T.; Cheng, V. C.; Chan, K. H.; Tsang, D. N.; Yung, R. W.; Ng, T. K.; Yuen, K. Y. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003, 361, 1319-1325 and references therein.
4. Rota, P. A.; Oberste, M. S.; Monroe, S. S.; Nix, W. A.; Campagnoli, R.; Icenogle, J. P.; Penaranda, S.; Bankamp, B.; Maher, K.; Chen, M. H.; Tong, S.; Tamin, A.; Lowe, L.; Frace, M.; DeRisi, J. L.; Chen, Q.; Wang, D.; Erdman, D. D.; Peret, T. C.; Burns, C.; Ksiazek, T. G.; Rollin, P. E.; Sanchez, A.; Liffick, S.; Holloway, B.; Limor, J.; McCaustland, K.; Olsen-Rasmussen, M.; Fouchier, R.; Gunther, S.; Osterhaus, A. D.; Drosten, C.; Pallansch, M. A.; Anderson, L. J.; Bellini, W. J. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003, 300, 1394-1399.
5. Thiel, V.; Ivanov, K. A.; Putics, A.; Hertzig, T.; Schelle, B.; Bayer, S.; Weissbrich, B.; Snijder, E. J.; Rabenau, H.; Doerr, H. W.; Gorbalenya, A. E.; Ziebuhr, J. Mechanisms and enzymes involved in SARS coronavirus genome expression. J. Gen. Virol. 2003, 84, 2305-2315.
6. (a) Anand, K.; Ziebuhr, J.; Wadhwani, P.; Mesters, J. R.; Hilgenfeld, R. Coronavirus main proteinase (3CL(pro)) structure: Basis for design of anti-SARS drugs. Science 2003, 300, 1763-1767.
7. (b) Anand, K.; Palm, G. J.; Mesters, J. R.; Siddell, S. G.; Ziebuhr, J.; Hilgenfeld, R. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. EMBO J. 2002, 21, 3213-3224.
8. Hegyi, A.; Ziebuhr, J. Conservation of substrate specificities among coronavirus main proteases. J. Gen. Virol. 2002, 83, 595-599
9. Matthews, D. A.; Dragovich, P. S.; Webber, S. E.; Fuhrman, S. A.; Patick, A. K.; Zalman, L. S.; Hendrickson, T. F.; Love, R. A.; Prins, T. J.; Marakovits, J. T.; Zhou, R.; Tikhe, J.; Ford, C. E.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; Binford, S. L.; Brothers, M. A.; DeLisle, D. M.; Worland, S. T. Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11000-11007.
10. Matthews, D. A.; Patick, A. K.; Baker, R. O.; Brothers, M. A.; Dragovich, P. S.; Hartmann, C. J.; Johnson, T. O.; Mucker, E. M.; Reich, S. H.; Rejto, P. A. J.; Rose, P. W.; Zwiers, S. H.; Huggins, J. W. In Vitro Antiviral Activity of Human Rhinovirus 3C Protease Inhibitors against the SARS Coronavirus; The National Academies Press: Washington, DC, 2004; Chapter 4, pp 186-193 (http://www.nap.edu/books/0309091543/html/186.html).
11. Ghosh, A. K.; Fidanze, S. Transition-state mimetics for HIV protease inhibitors: Stereocontrolled synthesis of hydroxyethylene and hydroxyethylamine isosteres by ester-derived titanium enolate syn and anti-aldol reactions. J. Org. Chem. 1998, 63, 6146-6154.
12. Kokotos, G.; Padron, J. M.; Martin, T.; Gibbons, W. A.; Martin, V. S. A general approach to the asymmetric synthesis of unsaturated lipidic α-amino acids. The first synthesis of α-aminoarachidonic acid. J. Org. Chem. 1998, 63, 3741-3744.
13. Hanessian, S.; Margarita, R. 1,3-Asymmetric induction in dianionic allylation reactions of amino acid derivatives. Synthesis of functionally useful enantiopure glutamates, pipecolates, and pyroglutamates. Tetrahedron Lett. 1998, 39, 5887-5890.
14. Secrist, J. A., III; Logue, M. W. Amine hydrochlorides in the reduction in the presence of chloroform. J. Org. Chem. 1972, 37, 335-336.
15. Tian, Q.; Nayyar, N. K.; Babu, S.; Chen, L.; Tao, J.; Lee S.; Tibbetts, A.; Moran, T.; Liou, J.; Guo, M.; Kennedy, T. P. An efficient synthesis of a key intermediate for the preparation of the rhinovirus protease inhibitor AG7088 via asymmetric dianionic cyanomethylation of N-Boc-L-(+)-glutamic acid dimethyl ester. Tetrahedron Lett. 2001, 42, 6807-609.
16. Baraldi, P. G.; Simoni, D.; Moroder, F.; Manfredini, S.; Mucchi, L.; Vecchia, F. D. Synthesis of 2-(5′-substituted isoxazol-3′-yl)-4-oxo- 3-thiazolidinyl alkanoic acids. J. Heterocycl. Chem. 1982, 19, 557-560.
17. inact and half-life T. Details of this assay will be published in due course.
18. Kim, J. C.; Spence, R. A.; Currier, P. F.; Lu, X.; Denison, M. R. Coronavirus protein processing and RNA synthesis is inhibited by the cysteine proteinase inhibitor E64d. Virology 1995, 208, 1-8.
19. Baker, R. O.; Bray, M.; Higgins, J. W. Potential antiviral therapeutics for smallpox, monkeypox and orthopoxvirus infections. Antiviral Res. 2003, 57, 13-20.
20. free values were 25.9% and 28.4%, respectively. The final model includes the inhibitor covalently linked to Cys145.