Cathepsin cysteine protease inhibitors

A method of treating osteoarthritis in a mammal in need thereof by administering to the mammal a therapeutically effective amount of a compound of the following chemical formula:

• wherein R1 is hydrogen, C1-6 alkyl or C2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C3-6 cycloalkyl, —SR9, —SR12, —SOR9, —SOR12, —SO2R9, —SO2R12, —SO2CH(R12)(R11), —OR12, —OR9, —N(R12)2, aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
• R2 is hydrogen, C1-6 alkyl or C2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C3-6 cycloalkyl, —SR9, —SR12, —SOR9, —SOR12, —SO2R9, —SO2R12, —SO2CH(R12)(R11), —OR12, —OR9, —N(R12)2, aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
• or R1 and R2 can be taken together with the carbon atom to which they are attached to form a C3-8 cycloalkyl or heterocyclyl ring wherein said ring system is optionally substituted with one or two substituents independently selected from C1-6 alkyl, hydroxyalkyl, haloalkyl, or halo;
• R3 is hydrogen, C1-6 alkyl or C2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C3-6 cycloalkyl or one to six halo;
• R4 is hydrogen, C1-6 alkyl or C2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C3-6 cycloalkyl or one to six halo;
• or R3 and R4 can be taken together with the carbon atom to which they are attached to form a C3-8 cycloalkyl ring, C5-8 cycloalkenyl ring, or five to seven membered heterocyclyl wherein said cycloalkyl, cycloalkenyl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
• R5 is selected from hydrogen or C1-6 alkyl substituted with 1-6 halo;
• R6 is aryl, heteroaryl, C1-6 haloalkyl, arylalkyl or heteroarylalkyl, wherein said aryl, heteroaryl, arylalkyl and heteroarylalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, haloalkoxy, —SR9, —SR12, —SOR9, —SOR12, —SO2R9, —SO2R12, —SO2CH(R12)(R11), —OR12, —N(R10)(R11), cyano, or aryl which is optionally substituted with —SO2R12;
• each D is independently C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, aryl, heteroaryl, C3-8 cycloalkyl or heterocyclyl wherein each said aryl, heteroaryl, cycloalkyl and heterocyclyl groups, which may be monocyclic or bicyclic, is optionally substituted on either the carbon or the heteroatom with one to five substituents independently selected from C1-6 alkyl, haloalkyl, halo, keto, alkoxy, —SR9, —SR12, —OR9, —OR12, N(R12)2, —SO2R9, or —SO2R10;
• R7 is hydrogen;
• R8 is hydrogen or C1-6 alkyl;
• or R4 and R8 or can be taken together with any of the atoms to which they may be attached or are between them to form a 4-10 membered heterocyclyl ring system wherein said ring system, which may be monocyclic or bicyclic, is optionally substituted with one or two substituents independently selected from C1-6 alkyl, halo, hydroxyalkyl, hydroxy, keto, —OR10, —SR10 or —N(R10)2;
• R9 is selected from the group consisting of hydrogen, aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, C3-8cycloalkyl, C3-8cycloalkyl(C1-4)alkyl, and heterocyclyl(C1-4)alkyl wherein said groups can be optionally substituted with one, two, or three substituents independently selected from halo, alkoxy or —SO2R12;
• R10 is hydrogen or C1-6 alkyl
• R11 is hydrogen or C1-6 alkyl;
• R12 is hydrogen or C1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo, alkoxy, cyano, —NR10 or —SR10;
• n is independently selected from an integer from one to three;
• or a pharmaceutically acceptable salt, stereoisomer or N-oxide derivative thereof.