The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors.

Sultam compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the KEAP1-Nrf2 interaction, such as inflammatory bowel disease, including Crohn's disease and ulcerative colitis.

Sultam compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the KEAP1-Nrf2 interaction, such as inflammatory bowel disease, including Crohn's disease and ulcerative colitis.

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, L, R.sup.2, R.sup.7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I. ##STR00001##

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, L, R.sup.2, R.sup.7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I. ##STR00001##

In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein R.sup.L, X, Y, R.sup.1A, R.sup.1B, R2, R3, m, and RA are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. ##STR00001##

In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein R.sup.L, X, Y, R.sup.1A, R.sup.1B, R2, R3, m, and RA are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. ##STR00001##

The invention provides modulators for the orphan nuclear receptor ROR.sub.γ and methods for treating ROR.sub.γ mediated diseases by administrating these novel ROR.sub.γ modulators to a human or a mammal in need thereof. Specifically, the present invention provides pyrrolo carboxamide compounds of Formula (1) and the enantiomers, diastereomers, N-oxides, tautomers, solvates and pharmaceutically acceptable salts thereof. ##STR00001##

The invention provides modulators for the orphan nuclear receptor ROR.sub.γ and methods for treating ROR.sub.γ mediated diseases by administrating these novel ROR.sub.γ modulators to a human or a mammal in need thereof. Specifically, the present invention provides pyrrolo carboxamide compounds of Formula (1) and the enantiomers, diastereomers, N-oxides, tautomers, solvates and pharmaceutically acceptable salts thereof. ##STR00001##

The present invention provides compounds of formula (I) and in particular 2-[bis(4-fluorophenyl)methyl]-2,7-diazaspiro[4.5]decan-10-one derivatives and related compounds as inhibitors of human dopamine-active-transporter (DAT) protein for the treatment of sexual dysfunction, affective disorders, anxiety, depression, chronic fatigue, Tourette syndrome, Angelman syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), obesity, pain, obsessive-compulsive disorder, movement disorders, CNS disorders, sleep disorders, narcolepsy, conduct disorder, substance abuse (including smoking cessation), eating disorders, and impulse control disorders.

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