Letters
J ournal of Medicinal Chemistry, 2004, Vol. 47, No. 20 4801
1994, 375, 343-347. (b) Palmer, J . T.; Rasnick, D.; Klaus, J . L.;
Bromme, D. Vinyl Sulfones as Mechanism-Based Cysteine
Protease Inhibitors. J . Med. Chem. 1995, 38, 3193-3196. (c)
Katunuma, N.; Murata, E.; Kakegawa, H.; Matsui, A. Tsuzuki,
H.; Tsuge, H.; Turk, D.; Turk, V.; Fukushima, M.; Tada, Y.; Asao,
T. Structure Based Development of Novel Specific Inhibitors for
Cathepsin L and Cathepsin S In Vitro and In Vivo. FEBS Lett.
1999, 458, 6-10. (d) Ward, Y. D.; Thomson, D. S.; Frye, L. L.;
Cywin, C. L.; Morwick, T. Emmanuel, M. J .; Zindell, R.; McNeil,
D.; Bekkali, Y.; Giradot, M.; Hrapchak, M.; DeTuri, M.; Crane,
K.; White, D.; Pav, S.; Wang, Y.; Hao, M.-H.; Grygon, C. A.;
Labadia, M. E.; Freeman, D. M.; Davidson, W.; Hopkins, J . L.;
Brown, M. L.; Spero, D. M. Design and Synthesis of Dipeptide
Nitriles as Reversible and Potent Cathepsin S Inhibitors. J . Med.
Chem. 2002, 45, 5471-5481. (e) Cywin, C. L.; Firestone, R. A.;
McNeil, D. W.; Grygon, C. A.; Crane, K. M.; White, D. M.;
Kinkade, P. R.; Hopkins, J . L.; Davidson, W.; Labadia, M. E.;
Wildeson, J .; Morelock, M. M.; Peterson, J . D.; Raymond, E. L.;
Brown, M. L.; Spero, D. M. The Design of Potent Hydrazones
and Disulfides as Cathepsin S Inhibitors. Bioorg. Med. Chem.
Lett. 2003, 11, 733-740. For a recent review, see: Leroy, V.;
Thurairatnam, S. Cathepsin S Inhibitors. Expert Opin. Ther.
Pat. 2004, 14, 301-311.
small molecule ligands that inhibit the activity of
cysteine proteases without relying upon covalent at-
tachment to the active site thiol represents a major
advance toward the development of small-molecule
therapeutics inhibiting this important class of protein
targets. Such compounds are anticipated to find utility
in the treatment of autoimmune diseases and allergies.9
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 1 and 2, experimental procedures for the
synthesis and characterization of 3a -f and 4, and descriptions
of the enzymatic and cellular assays. This material is available
Refer en ces
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