C. F. Thompson et al. / Bioorg. Med. Chem. Lett. 15 (2005) 2163–2167
2167
W.; Kym, P. R.; Kort, M. E. Ann. Rep. Med. Chem. 2002,
37, 167; (d) Kym, P. R.; Kort, M. E.; Coghlan, M. J.;
Moore, J. L.; Tang, R.; Ratajczyk, J. D.; Larson, D. P.;
Elmore, S. W.; Pratt, J. K.; Stashko, M. A.; Falls, D. H.;
Chun, W. L.; Nakane, M.; Miller, L.; Tyree, C. M.; Miner,
J. N.; Jacobson, P. B.; Wilcox, D. M.; Nguyen, P.; Lane,
B. C. J. Med. Chem. 2003, 46, 1016; (e) Coghlan, M. J.;
Jacobson, P. B.; Lane, B.; Nakane, M.; Lin, C. W.;
Elmore, S. W.; Kym, P. R.; Luly, J. R.; Carter, G. W.;
Russell, T.; Tyree, C. M.; Hu, J.; Elgort, M.; Rosen, J.;
Miner, J. N. Mol. Endocrinol. 2003, 17, 860; (f) Elmore, S.
W.; Pratt, J. K.; Coghlan, M. J.; Mao, Y.; Green, B. E.;
Anderson, D. D.; Stashko, M. A.; Lin, C. W.; Falls, D.;
Nakane, M.; Miller, L.; Tyree, C. M.; Miner, J. N.; Lane,
B. Bioorg. Med. Chem. Lett. 2004, 14, 1721; (g) Scha¨cke,
H.; Schottelius, A.; Do¨cke, W.-D.; Strehlke, P.; Jaroch, S.;
Norbert, S.; Rehwinkel, H.; Hennekes, H.; Asadullah, K.
PNAS 2004, 101, 227.
References and notes
1. For a leading reference on the history, receptor specificity,
mechanism, and side effects of glucocorticoids, see:
Schimmer, B. P.; Parker, K. L. In Goodman and GilmanÕs
The Pharmacological Basis of Therapeutics; Hardman, J.
G., Limbird, L. E., Gilman, A. G., Eds., 10th ed.; New
York: McGraw-Hill, 2001; pp 1649–1677.
2. Coghlan, M. J.; Elmore, S. W.; Kym, P. R.; Kort, M. E.
Curr. Top. Med. Chem. 2003, 3, 1617.
3. Schulz, M.; Eggert, M. Curr. Pharm. Des. 2004, 10, 2817.
4. Almawi, W. Y.; Melemedijian, O. K. J. Leukocyte Biol.
2002, 71, 9.
5. Herrlich, P. Oncogene 2001, 20, 2465.
6. Buckbinder, L.; Robinson, R. P. Curr. Drug Targets—
Inflamm. Allergy 2002, 1, 127.
7. Reichardt, H. M.; Tuckermann, J. P.; Go¨ttlicher, M.;
Vujic, M.; Weih, F.; Angel, P.; Herrlich, P.; Schutz, G.
¨
EMBO J. 2001, 20, 7168.
16. Preliminary experiments showed that dissociation in
mouse cell lines generally correlated well with dissociation
in human cell lines; rat cell lines did not correlate as well.
17. (a) Waage, A.; Slupphaug, G.; Shalaby, R. Eur. J.
Immunol. 1990, 20, 2439; (b) Ray, A.; Sehgal, P. B. J.
Am. Soc. Nephrol. 1992, 2, S214; (c) Ray, A.; Zhang,
D.-H.; Siegel, M. D.; Ray, P. Ann. N.Y. Acad. Sci. 1995,
762, 79.
8. Adcock, I. M. Pulm. Pharmacol. Therap. 2000, 13, 115.
9. Newton, R. Thorax 2000, 55, 603.
10. van der Burg, B.; Liden, J.; Okret, S.; Franck, D.; Wissing,
S.; van der Saag, P. T.; Gustafsson, J. Trends Endocrinol.
Metab. 1997, 8, 152.
11. Wade, E. J.; Heck, S.; Cato, A. C. B. Biochem. Soc. Trans.
1995, 23, 946.
18. Schmid, E.; Schmid, W.; Jantzen, M.; Mayer, D.; Jastorff,
B.; Schuntz, G. Eur. J. Biochem. 1987, 165, 499.
12. Go¨ttlicher, M.; Heck, S.; Herrlich, P. J. Mol. Med. 1998,
76, 480.
¨
19. Granner, D. K.; Tomkins, G. M. Methods Enzymol. 1970,
17A, 633.
20. Santoro, J. C.; Harris, G.; Sitlani, A. Anal. Biochem. 2001,
289, 18.
21. Gonzalez, J. C.; Johnson, D. C.; Morrison, D. C.;
Freudenberg, M. A.; Galanos, C.; Silverstein, R. Infect.
Immun. 1993, 61, 970.
22. A 7:1 mixture of aldehyde isomers favoring the desired
diastereomer was obtained.
23. Heteroaryl-lithium species were generated either by lithi-
um-halogen exchange of the corresponding bromide with
t-BuLi or deprotonation of the appropriate heterocycle
with n-BuLi.
13. Ali, A.; Thompson, C. F.; Balkovec, J. M.; Graham, D.
W.; Hammond, M. L.; Quraishi, N.; Tata, J. R.; Einstein,
M.; Ge, L.; Harris, G.; Kelly, T. M.; Mazur, P.; Pandit, S.;
Santoro, J.; Sitlani, A.; Wang, C.; Williamson, J.; Miller,
D. K.; Thompson, C. M.; Zaller, D. M.; Forrest, M. J.;
Carballo-Jane, E.; Luell, S. J. Med. Chem. 2004, 47, 2441.
14. Independently, Scanlan has discovered the same class of
dissociated glucocorticoids and reported on their activity;
see: Shah, N.; Scanlan, T. S. Bioorg. Med. Chem. Lett.
2004, 14, 5199.
15. For workon other classes of dissociated glucocorticoids,
see: (a) Ref. 2; (b) Coghlan, M. J.; Kort, M. E. Exp. Opin.
Ther. Pat. 1999, 9, 1525; (c) Coghlan, M. J.; Elmore, S.