Abstract: Compounds of the formula I wherein R1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy; or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10alkyl chain, C2-C4haloalkyl or C3-C7cycloalkylmethyl, R4 is Het, Carbocyclyl, optionally substituted as defined in the specification and pharmaceutically acceptable salts, hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain.

Abstract: Compounds of the formula I wherein R1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy; or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10alkyl chain, C2-C4haloalkyl or C3-C7cycloalkylmethyl, R4 is Het, Carbocyclyl, optionally substituted as defined in the specification and pharmaceutically acceptable salts, hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain

Abstract: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle; m is independently 0, 1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

Abstract: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

Abstract: Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus sych as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and 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 where the variables are as defined in the specification inhibit the NS3 protease of flavivirus such as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and 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: A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(?O)2; where Ra is H, C1-C4 alkyl or CH3C(?O); R5 is independently selected from H or methyl; E is —C(?O)—, —S(?O)m—, —NR5S(?O)m—, —NR5C(?O)—, —OC(?O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

Abstract: Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus such as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and 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 formula (I), wherein A′ and A″ are independently the same or different group of formula (II) wherein: R′ is H, CH3, C(CH3)2, —ORa, —N(Ra)2, —N(Ra)ORa or —DP; R′″ is H or CH3; Ra is H, C1-C3 alkyl; D is a bond, alkylene, —C(═O)—, —S(O)— or S(O)2—; P is an optionally substituted, mono or bicyclic carbo- or hetereocycle; R″ is H, any of the sidechains found in the natural amino acids, carboxacetamide, or a group (CH2)nDP; M is a bond or —C(═O)N(R′″)—; Q is absent, a bond, —CH(OH)— or CH2—; or R″ together with Q, M and R′ define an optionally substituted 5 or 6 membered carbo- or heterocyclic ring which is optionally fused with a further 5 or 6 membered carbo- or heterocyclic ring; with the proviso that R′ is —ORa, —, N(Ra)2, —N(Ra)ORa or -DP, if M is a bond and Q is absent; X is H, OH, OCH3, Y is H, OH, OCH3, but X and Y are

Abstract: Compounds of formula (I), wherein A and A are independently the same or different group of formula (II) wherein: R′ is H, CH3, C(CH3)2,—ORa, —N(Ra)2, —N(Ra)ORa or -DP; R is H or CH3; Ra is H, C1-C3 alkyl; D is a bond, alkylene, —C(═O)—, —S(O)— or S(O)2—; P is an optionally substituted, mono or bicyclic carbo- or hetereocycle; R″ is H, any of the sidechains found in the natural amino acids, carboxacetamide, or a group (CH2)nDP; M is a bond or —C(═O)N(R′″)-; Q is absent, a bond, —CH(OH)— or CH2—; or R″ together with Q, M and R define an optionally substituted 5 or 6 membered carbo- or heterocyclic ring which is optionally fused with a further 5 or 6 membered carbo- or heterocyclic ring; with the proviso that R is —ORa, -, N(Ra)2, —N(Ra)ORa or -DP, if M is a bond and Q is absent; X is H, OH, OCH3, Y is H, OH, OCH3, but X and Y are not both H; Z′ and Z″ are independently —(

Abstract: Compounds of the formula I: wherein: A′ and A″ are independently the same or different group of the formula II: wherein: R′ is H.