Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3 ; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteo

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteo

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3 ; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; Al is CH or N, A2 is CR6R7 or NR6, provided at least one of Aland A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

Abstract: Compounds of the formula wherein R1 and R2 are independently H, F or CH3 ; or R1 forms an ethynyl bond and R2 is H or C3-C8 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C8 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR8, provided at least one of A1 and A2 comprises N; R6 is H, C-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporo

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteo

Abstract: The invention provides compounds of the formula: which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3 ; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as oste

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or optionally substituted C3-C6 cycloalkyl; R3 is (optionally substituted) C1-C3 alkyl or C3-C6 cycloalkyl; R4 is methyl or fluoro; m is 0-2; E is optionally substituted thiazolyl; A1 and A2 together define an optionally substituted piperazine or piperidine ring have utility in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.