Discovery of novel conformationally restricted diazocan peptidomimetics as inhibitors of interleukin-1β synthesis

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 19, 2005, Pages 4291-4294

  Oppong, Kofi A ^a   Ellis, Christopher D ^a   Laufersweiler, Michael C ^a   O'Neil, Steven V ^a   Wang, Yili ^a   Soper, David L ^a   Baize, Mark W ^a   Wos, John A ^a   De, Biswanath ^a   Bosch, Gregory K ^a   Fancher, Amy N ^a   Lu, Wei ^a   Suchanek, Maureen K ^a   Wang, Richard L ^a   Demuth Jr , Thomas P ^a  

^a PROCTER AND GAMBLE PHARMACEUTICALS   (United States)

Author keywords

Caspase 1; Diazocan; ICE; Interleukin 1 ; Peptidomimetic

Indexed keywords

DIAZOCAN; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR; NITROGEN; UNCLASSIFIED DRUG;

ARTICLE; CELL ASSAY; CHEMICAL BOND; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

CASPASE 1; CASPASES; DIPEPTIDES; DRUG EVALUATION, PRECLINICAL; INHIBITORY CONCENTRATION 50; INTERLEUKIN-1; MOLECULAR CONFORMATION; MOLECULAR MIMICRY; PEPTIDES, CYCLIC; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 23944521822     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.050     Document Type: Article

References (27)

1. For a review on IL-1 biology, see: (a) C.A. Dinarello, and S.M. Wolff N. Engl. J. Med. 328 1993 106
2. J.P. Pelletier, J.A. DiBattistal, P. Roughley, R. McCollum, and J. Martel-Pelletier Rheum. Dis. Clin. North Am. 19 1993 545
3. F. Fernandez-Madrid, R.L. Karvonen, R.A. Teitge, P.R. Miller, and W.G. Negendank J. Magn. Reson. Imaging 12 1994 703
4. C.A. Dinarello, and S.M. Wolff N. Engl. J. Med. 328 1993 106
5. M.A. Ator, and R.E. Dolle Curr. Pharm. Des. 1 1995 191
6. K.P. Wilson, J. Black, J.A. Thompson, E.E. Kim, J.P. Griffith, M.A. Navia, M.A. Murcko, S.P. Chambers, J.P. Aldape, S.A. Raybuck, and D.J. Livingston Nature 370 1994 270
7. P.R. Sleath, R.C. Hendrickson, S.R. Kronheim, C.J. March, and R.A. Black J. Biol. Chem. 265 1990 14526
8. N. Saha, F. Moldovan, G. Tardif, J.P. Pelletier, J.M. Cloutier, and J. Martel-Pelletier Arthritis Rheum. 42 1999 1577
9. K. Rudolphi, N. Gerwin, N. Verzijl, P. Van der Kraan, and W. Van den Berg Osteoarthritis and Cartilage 11 2003 738
10. B. Bresnihan, J.M. Alvaro-Gracia, M. Cobby, M. Doherty, Z. Domljan, P. Emery, G. Nuki, K. Pavelka, R. Rau, B. Rozman, I. Watt, B. Williams, R. Aitchison, D. McCabe, and P. Musikic Arthritis Rheum. 42 1999 1781
11. N.A. Thornberry, E.P. Peterson, J.J. Zhao, A.D. Howard, P.R. Griffin, and K.T. Chapman Biochemistry 33 1992 3934
12. R.E. Dolle, C.V.C. Prasad, C.P. Prouty, J.M. Salvino, M.M.A. Awad, S.J. Schmidt, D. Hoyer, T.M. Ross, T.L. Graybill, G.J. Speier, J. Uhl, B.E. Miller, C.T. Helasek, and M.A. Ator J. Med. Chem. 40 1997 1941
13. Randle, J. C. Abstracts of Papers, 228th National Meeting of the American Chemical Society, Philadelphia, PA; American Chemical Society: Washington, DC, 2004; Abstract U944.
14. S. Hanessian, G. McNaughtonSmith, H.G. Lombart, and W.D. Lubell Tetrahedron 53 1997 12789
15. R. Hocquemiller, A. Cavè, and H.P. Husson Tetrahedron 33 1977 653
16. P.A. Evans, and B. Holmes Tetrahedron 47 1991 9131
17. U. Nubbemeyer Top. Curr. Chem. 216 2001 125
18. M.E. Maier Angew. Chem. Int. Ed. 39 2000 2073
19. J.A. Martinez-Perez, M.A. Pickel, E. Caroff, and W. Woggon Syn. Lett 12 1999 1875
20. O. Mitsunobu Synthesis 1 1981 1
21. The intermediate 8 is stable to column chromatography but decomposes over a period of one week when kept neat at room temperature. However it can be stored for extended periods as a cold solution in isopropanol.
22. Batchelor, M. J.; Bebbington, D.; Bemis, G. W.; Fridman, W. H.; Gillespie, R. J.; Golec, J. M. C.; Gu, Y.; Lauffer, D. J.; Livingston, D. J.; Matharu, S. S.; Mullican, M. D.; Murcko, M. A.; Murdoch, R.; Nyce, P. L.; Robidoux, A. L. C.; Su, M.; Wannamaker, M.; Wilson, K. P.; Zelle, R. E. PCT Intl. Appl. WO9722619, 1997.
23. Soper, D. L.; O'Neil, S. V.; Wang, Y.; Oppong, K. A.; Ellis, C. D.; Laufersweiler, M. C.; Demuth, T. P.; Fancher, A. N.; Lu, W.; Wang, R. L.; Schwecke, W. P.; Cruze, C. A.; Buchalova, M.; Belkin, M.; Wos, J. A. Abstracts of Papers, 228th National Meeting of the American Chemical Society, Philadelphia, PA; American Chemical Society: Washington DC 2004; Abstract U956.
24. Inhibition of IL-1β production in a cell-based assay: A suspension of human monocytic cells (THP-1, ATCC strain TIB202, 2 x 106/ml in RPMI 1640 medium from Gibco BRL) was plated in 96-well plates, incubated with or without compounds (administered as solutions in DMSO, such that test concentrations ranged from 1 nM to 10 μM) for 15 min, and then stimulated with LPS (1 μg/ml) for a total of 4 h. Cells were centrifuged and the conditioned media was collected to quantify the release of IL-1β by an ELISA measurement according to the manufacturer's instructions (R&D Systems, catalog number DLB50) or stored at -20°C for future use.
25. The values obtained for the free drug form of Pralnacasan® in our assays were comparable to those reported in similar bioassays see Rudolphi, K.; Gerwin, N.; Verzijl, N.; van der Kraan, P.; van den Berg, W. OsteoArthritis Cartilage, 2003, 11, 738 reference 5.
26. o was the initial velocity in the absence of inhibitor.
27. +.