Patent number: 6353017
Abstract: 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, R2, R3, R4, R5, X1, 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.
Type:
Grant
Filed:
August 22, 2000
Date of Patent:
March 5, 2002
Assignee:
Novartis AG
Inventors:
Eva Altmann, Claudia Betschart, Keigo Gohda, Miyuki Horiuchi, Rene Lattmann, Martin Missbach, Junichi Sakaki, Michihiro Takai, Naoki Teno, Scott Douglas Cowen, Paul David Greenspan, Leslie Wighton McQuire, Ruben Alberto Tommasi, John Henry van Duzer