Abstract: A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: R3 is selected from cyclopentyl and cyclohexyl; R9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high dual efficacies for human cathepsin S and K and are useful for the treatment of rheumatoid arthritis, osteoarthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, cardiovascular diseases which exhibit significant damage and remodeling of extracellular matrix (ECM) and chronic pain.

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein one of R1 and R2 is H, and the other is selected from C1-8-alkyl, C3-6-cycloalkyl and C1-8-alkyl-C5-10-aryl; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl and 1-methylcyclopentyl; R9 is selected from the following: wherein: R4 is selected from C1-8-alkyl and C3-8-cycloalkyl; G is selected from: CH, CMe and N; E is selected from: O, S, SO2, NH, NMe and N-oxide (N?O); J and R are independently selected from: CH, N and N-oxide (N?O); and R41 is selected from amino, methylamino, dimethylamino, isopropylamino, isopropyl(methyl)amino, cyclopropylamino, cyclopropyl(methyl)amino, cyclopentylamino, morpholino, piperidin-1-yl, piperidin-1-ylmethyl, morpholinomethyl, 4-methylpiperazin-1-yl, 4-(2-methoxyethyl)piperazin-1-yl, 1-morpholino ethyl, 1-(dimethylamino)ethyl, 1-(methylamino)ethyl, 4-fluoro-1-methylpyrrolidin-2-yl, 4,4-difluoropiperidin-

Abstract: A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: R3 is selected from cyclopentyl and cyclohexyl; R9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high dual efficacies for human cathepsin S and K and are useful for the treatment of rheumatoid arthritis, osteoarthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, cardiovascular diseases which exhibit significant damage and remodeling of extracellular matrix (ECM) and chronic pain.

Abstract: A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R3 and R4 is H, and the other is selected from C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C6-12-aralkyl; or R3 and R4 are each independently selected from C1-6-alkyl and halo; R9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof (I), wherein: R3 is cyclopentyl or cyclohexyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; and R4 is optionally substituted C3-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl, or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; and R8 is C1-8-alkyl or C3-8-cycloalkyl.

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; or R1 and R2 are both H; one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; or R3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; R8 is C1-8-alkyl or C3-8-cycloalkyl; R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R3 is tert-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R3 is tert-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (1), and pharmaceutically acceptable salts thereof, A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof (I), wherein: one of R1 and R2 is H, and the other is selected from F and Cl, or R1 and R2 are both F; R3 is selected from cyclopentyl and cyclohexyl; R4 is an optionally substituted 5- or 6-membered monocyclic or an 8- to 10-membered bicyclic aryl or heteroaryl ring which includes up to four heteroatoms. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: Compounds of general formula (I) or general formula (II):— wherein R1, P1, P2, Q, Y, (X)o, (W)n, (V)m, Z and U are as defined in the specification, are inhibitors of cruzipain and other cysteine protease inhibitors and are useful as therapeutic agents, for example in Chagas' disease, or for validating therapeutic target compounds.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; and R4 is optionally substituted C3-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl, or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; and R8 is C1-8-alkyl or C3-8-cycloalkyl.

Abstract: The present invention relates to a process for preparing a compound of formula (Ia), (Ib), (Ic) or (Id), or a pharmaceutically acceptable salt, hydrate, solvate, complex or prodrug thereof, said process comprising the steps of: (A) (i) treating a compound of formula (IVa), where R48 is alkyl or tosyl, with an oxidising agent to form a compound of formula (Va); and (ii) converting said compound of formula (Va) to a compound of formula (Ia) or (Ic); or (B) (i) treating a compound of formula (IVb), where R48 is alkyl or tosyl, with an oxidising agent to form a compound of formula (Vb); and (ii) converting said compound of formula (Vb) to a compound of formula (Ib) or (Id).

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof (I), wherein: R3 is cyclopentyl or cyclohexyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R3 is ten-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; or R1 and R2 are both H; one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; or R3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; R8 is C1-8-alkyl or C3-8-cycloalkyl; R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease and diseases involving matrix or cartilate degradation.

Abstract: The present invention relates to a process for preparing a compound of formula I, wherein R1 is Pg1 or P1?; P1? is CO-hydrocarbyl; P2 is CH2, O or N-Pg2; and Pg1 and Pg2 are each independently nitrogen protecting groups; (i) reacting a compound of formula II with a dioxirane to form an epoxide of formula III; where X is selected from CN, CH2N3, CH2NH-Pg2, ONH-Pg2, NHNH-Pg2, N(Pg2)NH-Pg2; (ii) converting a compound of formula III to a compound of formula I