Potent immunosuppressive C32-o-arylethyl ether derivatives of ascomycin with reduced toxicity

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 14, 1999, Pages 2089-2094

  Armstrong, Helen M ^a   Wong, Frederick ^a   Holmes, Mark A ^a   Sinclair, Peter J ^a   Goulet, Mark T ^a   Dumont, Francis J ^a   Staruch, MaryJo ^a   Koprak, Samuel ^a   Peterson, Laurence B ^a   Rosa, Raymond ^a   Wilusz, Mary Beth ^a   Wiederrecht, Gregory J ^a   Cryan, John G ^a   Wyvratt, Matthew J ^a   Parsons, William H ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASCOMYCIN; IMMUNOSUPPRESSIVE AGENT; TACROLIMUS;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; DRUG ACTIVITY; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE PROLIFERATION; MOUSE; NEPHROTOXICITY; NEUROTOXICITY; NONHUMAN;

ADMINISTRATION, ORAL; ANIMALS; CALCINEURIN; DRUG EVALUATION, PRECLINICAL; HYPOTHERMIA; IMMUNOPHILINS; IMMUNOSUPPRESSIVE AGENTS; INHIBITORY CONCENTRATION 50; INJECTIONS, INTRAVENOUS; KIDNEY DISEASES; MACROLIDES; MALE; MICE; MICE, INBRED BALB C; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES; TACROLIMUS; TACROLIMUS BINDING PROTEINS; TOXICITY TESTS;

EID: 0033584181     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00336-4     Document Type: Article

References (21)

1. Tanaka, H.; Kuroda, A.; Marusawa, H.; Hatanaka, H.; Kino, T.; Goto, T.; Hashimoto, M.; Taga, T. J. Am. Chem. Soc. 1987, 109, 5031.
2. Parsons, W. H.; Sigal, N. H.; Wyvratt, M. J. Ann. New York Acad. of Sci. 1993, 685, 22.
3. Dumont, F. J. In Drug Development in Transplantation and Autoimmunity; Leibermann, R. Muhkherjee, A. Eds.; R. G. Landes: Austin, TX, 1996; pp 175-205.
4. Dumont, F. J.; Staruch, M. J.; Koprak, S. L.; Siekeirka, J. J.; Lin, C. S.; Harrison, R.; Sewell, T.; Kindt, V. M.; Beattie, T. R.; Wyvratt, M. J.; Sigal, N. H. J. Exp. Med. 1992, 176, 751.
5. Lyson, T.; Ermel, L. D.; Belshaw, P. J.; Alberg, D. G.; Schreiber, S. L.; Victor, R. G. Circ. Res. 1993, 73, 596.
6. Sinclair, P. J.; Wong, F.; Wyvratt, M. J.; Staruch, M. J.; Dumont, F. Bioorg. Med. Chem. Lett. 1995, 5, 1035.
7. Sinclair, P. J.; Wong, F.; Staruch, M. J.; Wiederrecht, G.; Parsons, W. H.; Dumont, F.; Wyvratt, M. J. Bioorg. Med. Chem. Lett. 1996, 6, 2193.
8. Peterson, L. B.; Cryan, J. G.; Rosa, R.; Martin, M. M.; Wilusz, M. B.; Sinclair, P. J.; Wong, F.; Parsons, J. N.; O'Keefe, S. J.; Parsons, W. H.; Wyvratt, M. J.; Sigal, N. H.; Williamson, A. R.; Wiederrecht, G. J. Transplantation 1998, 65, 10.
9. Goulet, M. T.; Hodkey, D. W.; Staruch, M. J.; Dumont, F. J.; Cryan, J. G.; Parsons, W. H.; Wyvratt, M. J. Bioorg. Med. Chem. Lett. 1994, 4, 921.
10. Goulet, M. T.; McAlpine, S. R.; Staruch, M. J.; Koprak, S.; Dumont, F. J.; Cryan, J. G.; Wiederrecht, G. J.; Rosa, R.; Wilusz, M. B.; Peterson, L. B.; Wyvratt, M. J.; Parsons, W. H. Bioorg. Med. Chem. Lett. 1998, 8, 2253.
11. Byrne, K. M.; Shafiee, A.; Nielsen, J. B.; Arison, B.; Monaghan, R. L.; Kaplan, L. In Microbial Metabolites; Nash, C., Ed.; Developments in Industrial Microbiology Series, Vol. 32; W.C. Brown: Dubuque, 1992; pp 29-45.
12. Dumont, F. J.; Koprak, S.; Staruch, M. J.; Talento, A.; Koo, G.; DaSilva, C.; Sinclair, P. J.; Wong, F.; Woods, J.; Barker, J.; Pivnichny, J.; Singer, I.; Sigal, N. H.; Williamson, A. R.; Parsons, W. H.; Wyvratt, M. J. Transplantation 1998, 65, 18.
13. Goulet, M. T.; Sinclair, P. J.; Wong, F.; Staruch, M. J.; Dumont, F. J.; Cryan, J. G.; Wiederrecht, G. J.; Wyvratt, M. J.; Parsons, W. H. Bioorg. Med. Chem. Lett. 1999, 9, 2085.
14. Mathre, D. J.; Thompson, A. S.; Douglas, A. W.; Hoogsteen, K.; Carroll, J. D.; Corley, E. G.; Grabowski, E. J. J. J. Org. Chem. 1993, 58, 2880.
15. Becker, J.; Rotonda, J. unpublished results.
16. Assay conducted using murine splenic T-cells activated with PMA and ionomycin. In all cases the inhibition observed was reversed by the addition of exogenous IL-2, see: Dumont, F. J.; Staruch, M. J.; Koprak, S.; Melino, M. R.; Sigal, N. H. J. Immunol. 1990, 144, 251.
17. 17. Competitive binding assay using -dihydro FK-506, see: Siekierka, J. J.; Hung, S. H.; Pie, M.; Lin, C. S.; Sigal, N. H.; Nature 1989, 341, 755.
18. Liu, J.; Farmer, J. D.; Lane, W. S.; Friedman, J.; Wiessman, I.; Schreiber, S. L. Cell 1991, 66, 807.
19. Fruman, D. A.; Klee, C. B.; Bierer, B. E.; Burakoff, S. J. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3686.
20. O'Keefe, S. J.; Ramura, J.; Kincaid, R. L.; Tocci, M. J.; O'Neill, E. A. Nature 1992, 357, 692.
21. Asami, M.; Kuno, T.; Mukai, H.; Tanaka, C. Biochem. Biophys. Res. Commun. 1993, 192, 1388.