N-terminal substituted dipeptide nitriles as defined are useful as
inhibitors of cysteine cathepsins, e.g. cathepsins B, K, L and S, and can
be used for the treatment of cysteine cathepsin dependent diseases and
conditions, including inflammation, rheumatoid arthritis, osteoarthritis,
osteoporosis, tumors (especially tumor invasion and tumor metastasis),
coronary disease, atherosclerosis (including atherosclerotic plaque
rupture and destabilization). Particular dipeptide nitriles are compounds
of formula I, or physiologically-acceptable and -cleavable esters or a
salts thereof wherein: the symbols are as defined.
In particular it has been found that by appropriate choice of groups R,
R.sub.2, R.sub.3, R.sub.4, R.sub.5, X.sub.1, Y and L, the relative
selectivity of the compounds as inhibitors of the various cysteine
cathepsin types, e.g. cathepsins B, K, L and S may be altered, e.g. to
obtain inhibitors which selectively inhibit a particular cathepsin type
or combination of cathepsin types.