Abstract: Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein Ring A, Ring B, Ring C, R1, R2, R3, R4, R5, L, m, n, and p are as defined herein. The compounds are modulators of G-protein coupled receptor 88 (GPR88). Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases mediated by GPR88, including Tourette's Syndrome, Huntington's Disease (HD), Addiction, Parkinson's Disease (PD), Schizophrenia, Alzheimer's disease, and Attention Deficit Hyperactivity Disorder (ADHD).

Abstract: The present invention relates to a compound of formula (Ia), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X-Y is —NHSO2— or —SO2NH—; R1 is H or alkyl; R2 is selected from COOH and a tetrazolyl group; R3 is selected from H, Cl and alkyl; R4 is selected from H, Cl and F; R5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R6 is H; R7 is selected from H, CN, haloalkyl, Cl, F, SO2-alkyl, SO2NR13R14, optionally substituted heteroaryl and alkyl; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H, C1-C3-alkyl, or halo; R10 and R11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R10 and R11,

Abstract: The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR12R13; or one of P and Q is NR14 and the other is CR12R13; the group X—Y is —NHSO2— or —SO2NH—; R1 is H, CN or alkyl; R2 is selected from COOH and a tetrazolyl group; R3 is selected from H, Cl and alkyl; R4 is selected from H and halo; R5 is selected from H, alkyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R6 is H; R7 is selected from H, CN, haloalkyl, halo, SO2-alkyl, heteroaryl, SO2NR16R17, CONR10R11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H or halo; and R10, R11, R12, R13, R14, R

Abstract: The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO2— or —SO2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R1 is H or alkyl; R2 is selected from COOH and a tetrazolyl group; R3 is selected from H, C land alkyl; R4 is selected from H and halo; R5 is selected from H, alkyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R6 is H; R7 is selected from H, CN, haloalkyl, halo, SO2-alkyl, SO2NR12R13, heteroaryl, CONR10R11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R8 is selected from H, alkyl, haloalkyl and halo; and R9 is H, alkyl or halo; R10 and R11 are each independently H or alkyl; and R12 and R1

Abstract: The invention relates to improved ANTISENSE agents for the treatment of gram-negative bacterial infections. Compounds of the invention utilise an Antibiotic-Assisted Translocation; AAT? platform to improve influx into bacterial cells through enhanced permeability, providing improved intracellular exposure of the ANTISENSE AGENT and superior treatment of the infection.

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: 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: 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-(dimethyl amino)ethyl, 1-(methyl amino)ethyl, 4-fluoro-1-methylpyrrolidin-2-yl, 4,4-difluoropiperi

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: 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-morpholinoethyl, 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: 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, 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: 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: 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: 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-morpholinoethyl, 1-(dimethylamino)ethyl, 1-(methylamino)ethyl, 4-fluoro-1-methylpyrrolidin-2-yl, 4,4-difluoropiperidin-

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-morpholinoethyl, 1-(dimethylamino)ethyl, 1-(methylamino)ethyl, 4-fluoro-1-methylpyrrolidin-2-yl, 4,4-difluoropiperidin-1

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 prodrugs of a wide variety of drugs and pharmaceutical compositions containing such prodrugs. Methods for minimizing locally mediated (from within the gut lumen) adverse gastrointestinal events associated with the underivatised drug and increasing the sustainment of plasma drug levels with the aforementioned prodrugs are also provided. Thus, the present invention relates to the use of prodrugs of a wide diversity of drugs (other than opioids) to transiently inactivate them and so reduce directly, locally mediated adverse gastrointestinal (GI) side-effects normally evident after administration of the parent compound. Additionally, such prodrugs may confer improved pharmacokinetics.

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 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 oxidizing 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 oxidizing agent to form a compound of formula (Vb); and (ii) converting said compound of formula (Vb) to a compound of formula (Ib) or (Id).