Alzheimer's disease

BACE1 INHIBITORS (Fri, 17 Feb 2017)
The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 17 Feb 2017)
A compound of Formula (I) is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula (I) as TD02 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula (I).
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8-HYDROXYQUINOLINE DERIVATIVES AS DIAGNOSTIC AND THERAPEUTIC AGENTS (Fri, 17 Feb 2017)
The present application provides compounds useful in methods of treating neurological disorders such as Alzheimer's disease, and cancer such as prostate cancer. Also provided herein are radiolabeled compounds useful for imaging techniques, and techniques for diagnosis and monitoring of treatment of neurological disorders and cancer. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography or single- photon emission computed tomography. Methods for preparing radiolabeled compounds and methods for preparing unlabeled compounds are also provided.
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COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING NEURODEGENERATIVE DISORDERS (Fri, 17 Feb 2017)
Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.
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BROAD SPECTRUM REACTIVATORS OF OPNA-INHIBITION OF HUMAN CHOLINESTERASES (Fri, 10 Feb 2017)
The present invention deals with novel compounds which are reactivators of human acetylcholinesterase, pharmaceutical compositions comprising said compounds, and their use in the treatment of a nervous and/or respiratory failure due to intoxication with at least one organophosphorous nerve agent such as warfare agents and pesticides. It also pertains to these compounds for use in the treatment of neurological diseases such as Alzheimer's disease.
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 10 Feb 2017)
The present invention provides, in part, compounds of Formula I and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 10 Feb 2017)
Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.
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VINYL FLUORIDE CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 10 Feb 2017)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A7, and each of Ra, Rb, R1, R2, R3, R8 R9 and R10 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions.
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.98mm" wi="62.91mm" file="US20170029390A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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2-SUBSTITUTED-5-HYDROXY-4H-CHROMEN-4-ONES AS NOVEL LIGANDS FOR THE SEROTONIN RECEPTOR 2B (5-HT2B) (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">A family of compounds which function as selective ligands for the serotonin receptor 2B (5-HT<sub>2B</sub>) is identified. Some of the compounds are synthetic non-natural ligands which have a relatively strong interaction with 5-HT2B compared to naturally occurring compounds (some of which are identified for the first time herein as ligands for 5-HT<sub>2B</sub>). Because the compounds, both naturally occurring and synthetically produced, function as ligands for 5-HT<sub>2B </sub>they will have application in, for example, the treatment and/or prevention of nervous system disorders such as Alzheimer's disease.</p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.23mm" wi="69.85mm" file="US20170029417A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.57mm" wi="53.76mm" file="US20170027921A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as described in the specification, or a salt thereof.</p>
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USE OF N-(4-ISOPROPYLPHENYL)-5-AMINO-ISOINDOLINE (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to a novel use of N-(4-isopropylphenyl)-5-amino-isoindoline for diagnosing Alzheimer's disease and quantifying amyloid in the brain.</p>
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Feb 2017)
The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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ANTI-NEUROINFLAMMATORY AND PROTECTIVE COMPOUNDS IN ACHILLEA FRAGRANTISSIMA (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">The invention relates to 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TIF) and achillolid A in prevention or treatment of Alzheimer's disease as well as other neurodegenerative diseases such as Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), ischemia, immunodeficiency virus-1 (HTV-1)-associated dementia, Lewy body associated dementia, traumatic brain injury (TBI), glioma, epilepsy. Huntington's disease, multiple sclerosis, glaucoma and schizophrenia where neuroinflammation, oxidative stress, glutamate toxicity and amyloid beta toxicity are part of the pathophysiology.</p>
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Novel Forms of [R-(R*,R*)]-2-(4-Fluorophenyl)-Beta, Gamma-Dihydroxy-5-(1-Methylethyl)-3-Phenyl-4-[(Phenylamino)carbonyl]-1H-Pyrrole-1-Heptanoic Acid Calcium Salt (2:1) (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Novel forms of [R, (R*,R*)]-<b>2</b>-(<b>4</b>-Fluorophenyl)-β,δdihydroxy-<b>5</b>-methylethyl)-<b>3</b>-phenyl-<b>4</b>-[(phenylamino)carbonyl]-<b>1</b>-H-pyrrole-<b>1</b>-heptanoic acid hemi calcium salt designated Form XX, Form XXI, Form XXII, Form XXIII, Form XXIV, Forms XXV, Form XXVII, Form XXVIII, Form XXXIX, and Forms XXX, characterized by their X-ray powder diffractor, solid state NMR, and/or Raman spectroscopy are describes as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia (BPH) and Alzheimer) disease.</p>
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COMPOUNDS (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).</p>
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BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABA<sub>A </sub>receptor agonist (e.g., a α5-containing GABA<sub>A </sub>receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction.</p>
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COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia.</p>
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PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Isolated or pure compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including but not limited to psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing an isolated or pure compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.</p>
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HETEROCYCLIC COMPOUND AND USE THEREOF (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Provided is a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.35mm" wi="69.85mm" file="US20170022222A1-20170126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the specification, or a salt thereof, which has an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action. The compound of the present invention is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like.</p>
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PRODRUG OF AN ICE INHIBITOR (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">This invention describes an ICE inhibitor prodrug (I) having good bioavailability.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.02mm" wi="73.74mm" file="US20170022249A1-20170126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.</p>
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COMPOUNDS (Fri, 27 Jan 2017)
Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
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CRYSTAL FORMS OF TETRA-HYDRO-N, N-DIMETHYL-2, 2-DIPHENYL-3-FURANMETHANAMINE HYDROCHLORIDE, PROCESSES FOR MAKING SUCH FORMS, AND THEIR PHARMACEUTICAL COMPOSITIONS (Fri, 27 Jan 2017)
Polymorphic forms of tetrahydro-N,N-dimethyl-2,2-diphenyl-3- furanmethanamine hydrochloride (ANAVEX2-73) and a metabolite of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) are disclosed and characterized. Compositions and method for treatment of Alzheimer's disease that includes the polymorphic forms and metabolite of tetrahydro-N,N-dimethyl-2,2- diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73).
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COMPOUNDS (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).</p>
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METHODS AND COMPOSITIONS COMPRISING TAU OLIGOMERS (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught. Methods for producing and purifying these structures for the development of small molecule and immunotherapeutics as well as antibodies for biomarkers of neurodegenerative diseases are taught.</p>
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Antibodies Specific for Hyperphosphorylated Tau and Methods of Use Thereof (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to a novel class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396), as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and tauopathies.</p>
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ANTIBODIES SPECIFIC FOR HYPERPHOSPHORYLATED TAU AND METHODS OF USE THEREOF (Fri, 20 Jan 2017)
The present invention relates to a novel class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396), as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and tauopathies.
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NOVEL IMAGING COMPOUNDS (Fri, 20 Jan 2017)
The present invention relates to novel compounds that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.
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DIHYDROPYRIDOPYRROLE DERIVATIVES AS TAU-PET-LIGANDS (Thu, 19 Jan 2017)
The present invention relates to novel compounds of formula (I) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other Tauopathies using Positron Emission Tomography (PET) Imaging. Formula (I):
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QUINOLINE COMPOUNDS (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to quinoline compounds as defined by Formula I below. Such quinoline compounds have been shown to inhibit the formation of amyloid deposits (e.g., amyloid oligomers, fibrils or plaques). Consequently, these compounds are suitable for treating a range of diseases and disorders in which amyloid deposits are implicated, such as type-2 diabetes and Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="63.42mm" file="US20170008849A1-20170112-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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THERAPEUTIC COMPOUNDS (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.</p>
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PYRIDAZIN-3(2H)-ONE DERIVATIVES WHICH ARE SELECTIVE INHIBITORS OF THE ISOFORM B OF MONOAMINE OXIDASE (Thu, 12 Jan 2017)
The present invention refers to pyridazin-3(2H)-one derivatives of general structure I, II and III, which are selective MAO-B inhibitors, and to the use thereof for preparing pharmaceutical compositions intended to treat disorders derived from MAO-B hyperactivity, particularly degenerative disorders of the central nervous system (CNS), such as Parkinson's disease (PD), Alzheimer's disease (AD) and other dementias. These are pyridazin-3(2H)-one derivatives having dithiocarbamate moieties bonded to position 4, 5 or 6 through an alkyl chain of variable length (n=1, 2, 3). This invention is also directed to the preparation of said compounds.
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Carbazole and Carboline Compounds for Use in the Diagnosis, Treatment, Alleviation or Prevention of Disorders Associated with Amyloid or Amyloid-Like Proteins (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that can be employed in the diagnosis, treatment, alleviation or prevention of a group of disorders and abnormalities associated with amyloid proteins and amyloid-like proteins, such as Alzheimer's disease. Precursors for the preparation of the compounds according to the present invention are also provided.</p>
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NOVEL 3,4-DISUBSTITUTED-1H-PYRROLO[2,3-b]PYRIDINES AND 4,5-DISUBSTITUTED-7H-PYRROLO[2,3-c]PYRIDAZINES AS LRRK2 INHIBITORS (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention provides novel 3,4-disubstituted-1H-pyrrolo[2,3-b]pyridine derivatives and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazine derivatives of Formula I, and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.94mm" wi="54.53mm" file="US20170002000A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and X are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.</p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US20170001994A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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MOLECULAR RE-ENGINEERING OF EXCITATION-INHIBITION BALANCE IN MEMORY CIRCUITS (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">Disclosed are memory-regulating agents and methods that target actin binding LIM protein family, member 3 (ABLIM3). Specifically, the disclosure provides methods of inhibiting Ablim3 using inhibitory nucleic acids that target the Ablim3 gene or mRNA to improve memory in subjects with memory dysfunction associated with Alzheimer's Disease (AD), normal aging, or posttraumatic stress disorder (PTSD). Further disclosed is a cell-based assay that can be used to screen for small molecule regulat ors of Ablim3 function.</p>
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Omegabalins, GABA Derivatives of Omega-3 Polyunsaturated Acids, Their Formulations and Methods of Use (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to omegabalins, which are GABA derivatives of omega-3 fatty acids, and their use in pharmaceutically-acceptable formulations for treating neuropathic pain, fibromyalgia, epilepsy, anxiety, depression, insomnia, Alzheimer's disease, and other neurological conditions.</p>
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HETEROCYCLIC COMPOUND (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.18mm" wi="69.85mm" file="US20160376244A1-20161229-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the attached DESCRIPTION.</p>
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2,3-DIHYDRO-4H-1,3-BENZOXAZIN-4-ONE DERIVATIVES AS MODULATORS OF CHOLINERGIC MUSCARINIC M1 RECEPTOR (Fri, 30 Dec 2016)
The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof: wherein each symbol is as defined in the attached DESCRIPTION.
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Substituted pyrido[2,3-b]pyrazines as phosphodiesterase 2A inhibitors (Wed, 28 Dec 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a PDE2A selective inhibitory action, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like.</p> <p id="p-0002" num="0000">The present invention is a compound represented by the formula (1):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="57.74mm" file="US09527841-20161227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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BIS-FURAN DERIVATIVES AS TRANSTHYRETIN (TTR) STABILIZERS AND AMYLOID INHIBITORS FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY (FAP) (Fri, 23 Dec 2016)
The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloid polyneuropathy (FAP), despite their lower molecular weight and lipophilicity. Moreover, ex vivo experiments with the strongest inhibitor in the series, conducted in human blood plasma from normal and FAP Val30Met-transthyretin carriers, disclose remarkable affinity and selectivity profiles. The promises and challenges facing further development of this compound are discussed under the light of increasing evidence implicating transthyretin stability as a key factor not only in transthyretin amyloidoses and several associated co-morbidities, but also in Alzheimer's disease.
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PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds (referred to herein as “PPDA compounds”) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.</p>
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METHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN AGGREGATION (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a <i>Caenorhabditis elegans </i>model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.</p>
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Pro-Neurogenic Compounds (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.</p>
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INHIBITORS OF COGNITIVE DECLINE (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimer's disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimer's disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.</p>
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NEW COMPOUNDS HAVING A SELECTIVE PDE4D INHIBITING ACTIVITY (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Compounds of formula (I), wherein Z=cyclopentyl. cyclopropylmethyl, —CH<sub>3</sub>; R′=—CH<sub>3</sub>, CHF<sub>2</sub>, X=formula (II) (III) (IV) (V) Y=—CO; —C═O(CH<sub>2</sub>), —CH(OH)—CH<sub>2</sub>, —CH<sub>2</sub>—C═O, —CH<sub>2</sub>—CH<sub>2</sub>—C═O; —CH<sub>2</sub>—CH(OH)—CH<sub>2</sub>, —CH<sub>2</sub>—CH(OCOR<sub>1</sub>)—CH<sub>2 </sub>NR<sub>2</sub>=—N(CH<sub>2</sub>—CH<sub>2</sub>OH)<sub>2</sub>, formula (VI) (VII) (VIII) (IX) (X) (XI) R<sub>1</sub>=optionally substituted C<sub>1</sub>-C<sub>8 </sub>alkyl, optionally substituted aryl; optionally substituted aralkyl, preferably C<sub>1</sub>-C<sub>3 </sub>alkyl, more preferably CH<sub>3</sub>; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof; these compounds have a PDE4D inhibiting activity and can be used as a medicament for treating dementia, in particular Alzheimer disease, and for improving memory.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="229.95mm" wi="72.22mm" file="US20160355489A1-20161208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="47.33mm" wi="49.19mm" file="US20160355489A1-20161208-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.</p>
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3-(6-CHLORO-3-OXO-3,4-DIHYDRO-(2H)-1,4-BENZOXAZIN-4-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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3-(5-CHLORO-2-OXO-2,3-DIHYDRO-1,3-BENZOTHIAZOL-3-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 02 Dec 2016)
The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.
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METHOD OF DIAGNOSIS, PROGNOSTIC OR TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">Methods for the diagnosis and prognosis of neurodegenerative diseases, such as Alzheimer's disease, are described. Compositions and method for the treatment of neurodegenerative diseases are also described.</p>
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METHODS OF TREATING NEUROLOGICAL, METABOLIC, AND OTHER DISORDERS USING ENANTIOPURE DEUTERIUM-ENRICHED PIOGLITAZONE (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The invention provides enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating neurological disorders, cancer, respiratory disorders, metabolic disorders, and other disorders using enantiopure deuterium-enriched pioglitazone. A preferred aspect of the invention provides methods of treating Alzheimer's disease, non-small cell lung cancer, hepatocellular carcinoma, and chronic obstructive pulmonary disease using enantiopure deuterium-enriched pioglitazone.</p>
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FUSED IMIDAZOLE COMPOUNDS (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABA<sub>A </sub>α5) and act as GABA<sub>A </sub>α5 negative allosteric modulators (GABA<sub>A </sub>α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABA<sub>A </sub>α5 such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="69.85mm" file="US20160331757A1-20161117-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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QUINOLINE DERIVATIVES FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER'S DISEASE (Fri, 18 Nov 2016)
A new class of quinoline compounds is useful for the detection and treatment of Alzheimer's disease and other neurodegenerative diseases such as amyloidoses and tauopathies. The compounds can be synthesized in radiolabeled form for use as imaging agents, which can be used for early detection of aggregates in the brain or other tissues prior to onset of symptoms, allowing early therapeutic intervention. The compounds are also useful for the prevention and treatment of such diseases.
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A CASEIN KINASE 1 DELTA INHIBITOR (Fri, 18 Nov 2016)
The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl) carbonyl] indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.
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4H-PYRAN COMPOUNDS AS INSULIN-REGULATED AMINOPEPTIDASE (IRAP) INHIBITORS (Fri, 18 Nov 2016)
The present disclosure relates to 4H-pyran compounds of formula (I) and their use in therapy, to compositions and agents comprising said compounds, to methods of treatment using said compounds, and their use in the manufacture of medicaments. The disclosure further relates to said compounds and compositions thereof as inhibitors of IRAP and their use in the treatment or prevention of Alzheimer's disease and the treatment and prevention of memory and cognitive disorders.
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5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula I′ having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.28mm" wi="55.63mm" file="US20160318952A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1H-PYRAZOLO[3,4-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">Provided herein are compounds according to Formulas (I) or (II) and pharmaceutically acceptable salts thereof, and compositions comprising the same, for use in various methods, including treating cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, osteoarthritis, idiopathic pulmonary fibrosis and neurological conditions/disorders/diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="103.97mm" wi="63.25mm" file="US20160318954A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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URIDINE DIPHOSPHATE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISORDERS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">This disclosure relates to uridine di phosphate (UDP) derivatives, compositions comprising therapeutically effective amounts of those UDP derivatives and methods of using those derivatives or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease) and traumatic CNS injury, as well as pain.</p>
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4-(PIPERRAZIN-1-YL)-PYRROLIDIN-2-ONE COMPOUNDS AS MONOACYLGLYCEROL LIPASE (MAGL) INHIBITORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention aims to provide a compound having an MAGL inhibitory action, and useful as a prophylactic or therapeutic agent for neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis and the like), anxiety disorder, pain (e.g., inflammatory pain, carcinomatous pain, nervous pain and the like), epilepsy and the like. The present invention relates to a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.19mm" wi="69.85mm" file="US20160318864A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the DESCRIPTION, or a salt thereof.</p>
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3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL) PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">A compound of formula (I) or a salt thereof are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="57.40mm" file="US20160318884A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, X and R<sup>3 </sup>are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.</p>
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P-GP RADIOTRACERS FOR IMAGING AS BIOMARKER INVOLVED IN ONSET OF NEURODEGENERATIVE DISEASES (Fri, 04 Nov 2016)
The invention includes a new class of radiolabeled compounds of formula I able to bind P-glycoprotein with high affinity and selectivity. The protein prevents accumulation in the brain of a wide range of drugs and, changes in P-gp expression and function, are also believed to occur in several neurological disorder, such as Alzheimer's disease (AD). Indeed, it is widely reported that decreased expression of P- gp and/or activity at the BBB level could cause accumulation of I3- amyloid plaques, the main hallmark of AD onset. 13-amyloid is a P-gp substrate, and these results support the importance of P-gp in the clearance of 13-amyloid peptide from brain parenchyma. For this reason, P-gp can be considered a useful biomarker for the early diagnosis of neurodegeneration. There is considerable interest in the development of P-gp PET radiotracers for imaging expression and function of P-gp. Formula I wherein the compound is labeled with an isotope selected from H, 11C 14C, 13N, 150 18F 19F, 75Br, 76Br, 79Br.
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 04 Nov 2016)
Provided in some embodiments are compounds herein. Also provided in some embodiments are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided in some embodiments are compositions comprising a compound herein, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a compound herein, optionally in combination with a supplemental agent.
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US20160311814A1-20161027-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US20160311808A1-20161027-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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ALPHA B-CRYSTALLIN FOR USE IN TREATING GLUTAMATE EXCITOTOXICITY OR TAUOPATHIES (Fri, 28 Oct 2016)
The present invention describes a compound for use in treating or preventing glutamate excitotoxicity and/or tauopathy in a subject, preferably a disorder selected from the group of epilepsy, spinal cord injury, stroke, traumatic brain injury, Alzheimer's disease, Pick's disease, amyotrophic lateral sclerosis, frontotemporal dementia, frontotemporal lobar degeneration, progressive supranuclear palsy, Parkinsonism linked to chromosome 17, cortical basal degeneration, hearing loss, and in alcoholism or alcohol withdrawal problems, wherein said compound comprises a small heat shock protein having an alpha-crystallin domain, and methods for treating or preventing glutamate excitotoxicity and/or tauopathy in a subject, using said compound.
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PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS (Fri, 28 Oct 2016)
Isolated or pure compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including but not limited to psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing an isolated or pure compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
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COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 28 Oct 2016)
The present invention relates to compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, Y, Z, Q, W, m, u, ring (A), R2, R3, R4, R5 and R6, are as defined in the specification and claims. The present invention provides a pharmaceutical composition containing the compounds of Formula (I) and a therapeutic method of treating and/or preventing Downs syndrome, β-amyloid angiopathy, disorders associated with cognitive impairment, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegenerative diseases, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, Alzheimer's disease and/or Down syndrome, age-related macular degeneration (AMD), glaucoma, olfactory function impairment, traumatic brain injury, progressive muscle diseases, Type II diabetes mellitus and cardiovascular diseases (stroke).
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METHOD FOR PREPARING THE ANHYDROUS CRYSTALLINE FORM OF ISONIAZID-DERIVED HYDRAZONE, THUS PRODUCED CRYSTALLINE POLYMORPH OF THE ANHYDROUS FORM, USE THEREOF FOR THE TREATMENT OF ALZHEIMER'S DISEASE, PARKINSONISM AND OTHER NEURODEGENERATIVE DISORDERS, AND PHARMACEUTICAL COMPOSITION (Thu, 27 Oct 2016)
The present invention relates to the method for preparing the anhydrous crystalline form of isoniazid-derived hydrazone (8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone), to the thus produced polymorph and to the use thereof for the treatment of Alzheimer's disease and parkinsonism, inter alia, and to a pharmaceutical composition.
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COMPOSITIONS AND METHODS TO ASSESS THE CAPACITY OF HDL TO SUPPORT REVERSE CHOLESTEROL TRANSPORT (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The invention provides compositions and methods for assessing the capacity of high density lipoprotein (HDL) to support reverse cholesterol transport in blood by measuring exchange if HDL-specific spin-labeled lipoprotein probes and electron paramagnetic spectroscopy. The invention also provides methods to identify individuals at risk for cardiovascular disease, to monitor the treatment of cardiovascular disease and in the development of therapies to treat cardiovascular disease. The invention also provides methods to identify individuals at risk for Alzheimer's disease, to monitor the treatment of Alzheimer's disease and in the development of therapies to treat Alzheimer's disease.</p>
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GAMMA SECRETASE MODULATORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">Disclosed herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the compound of Formula (I) and use of the compound in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="63.08mm" file="US20160304534A1-20161020-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL COMPOUNDS AS JNK KINASE INHIBITORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to modulators, such as inhibitors, of JNK isoform 2 (JNK2) or isoform 3 (JNK3) comprising compounds of formula (I) or formula (II) as described herein. Compounds of the invention can be used for treatment of a medical disorder in a patient wherein modulation of JNK3 is medically indicated, such as when the disorder is Parkinson disease (PD) Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), myocardial infarction (MI), glaucoma, obesity, diabetes, cancer, rheumatoid arthritis, fibrotic disease, pulmonary fibrosis, kidney disease, liver inflammation, Crohns disease, hearing loss, Prader Willi syndrome, or a condition where modification of feeding behavior is medically indicated.</p>
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COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 21 Oct 2016)
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
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IMMUNOLOGICAL METHODS AND COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to immunogenic compositions and peptides comprising residues 4-10 (FRHDSGY) of the amyloid peptide Abeta<sub>42</sub>. The invention further relates to antibodies that bind to the Abeta<sub>(4-10) </sub>antigenic determinant. The invention provides methods for treating Alzheimer's disease and for reducing the amyloid load in Alzheimers patients. The invention also relates to methods for designing small molecule inhibitors of amyloid deposition.</p>
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S1P3 ANTAGONISTS (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to antagonists of the S1P3 receptor formula (A) as herein described and pharmaceutical compositions thereof. The compounds of formula (A) are useful in the preparation of a medicament, in particular for the treatment of Alzheimer's disease.</p>
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INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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SPIROCYCLIC COMPOUNDS CONTAINING SPIRO[INDOLYL-3,1'-PYRROLO[3,4-C]PYRROLE] CORE AND SULPHUR-CONTAINING AMINO ACID RESIDUES (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to spirocyclic compounds on the basis of 2-oxindole derivatives containing a spiro[indolyl-3,1′-pyrrolo[3,4-c]-pyrrole] core and biogenic sulphur-containing amino acid residues, which display a glucocorticoid-mimicking action by influencing 11β-HSD1 enzyme cortisone->cortisol conversion, or by inhibiting GRs- or GITR- or mineralocorticoid receptors, or other targets, but do not interfere with steroidal haemostasis in HPA; and compositions containing same and their use for therapy as part of undifferentiated stroke therapy (in the absence of final verification of the stroke subtype) at various stages of acute ischemic stroke (AIS), during the period of recovery from stroke and craniocerebral trauma, in patients with chronic cerebrovascular pathology (against a background of diabetes), in combinational therapy for Alzheimer's disease and encephalopathy of various origin (discirculatory, alcoholic, infectious-toxic), and diabetes, combinational therapy for retinal degenerative eye diseases, as part of combinational therapy for metabolic syndrome (obesity, in patients suffering from Cushing's syndrome, Reaven metabolic syndrome (also known as syndrome X or insulin resistance syndrome) and other diseases where GCs hormones play a key role.</p>
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Process for large scale production of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">A process suitable for adoption to large scale manufacture of 1-[(2-bromophenyl-sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate, which is a selective 5-HT<sub>6 </sub>receptor antagonist intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.</p>
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HYBRID COMPOUNDS OF CURCUMIN AND MELATONIN AS NEUROPROTECTANTS FOR NEURODEGENERATIVE DISORDERS (Fri, 07 Oct 2016)
<p id="p-0001" num="0000">Hybrid compounds of curcumin and melatonin as neuroprotectants are provided. The hybrid compounds are useful for the treatment and/or prevention of Alzheimer's disease (AD), as well as other neurodegenerative diseases. The hybrid compounds exhibited superior and potent neuroprotection in an AD model.</p>
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METHODS AND MATERIALS FOR REDUCING AMYLOID BETA LEVELS WITHIN A MAMMAL (Fri, 07 Oct 2016)
This document provides methods and materials for reducing amyloid beta levels within a mammal (e.g. a mammal having Alzheimer's disease). For example, this document provides methods for using compositions containing a potato polysaccharide preparation to reduce one or more symptoms of Alzheimer's disease. In some cases, a composition containing a potato polysaccharide preparation provided herein can be used to increase binding, sequestration, and/or degradation of CNS-derived amyloid beta polypeptides, thereby inhibiting the formation of neurofibrillary plaques.
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PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.40mm" wi="56.47mm" file="US20160280695A1-20160929-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein variables A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, A<sup>8</sup>, each of R<sup>a</sup>, R<sup>b</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>7 </sup>of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.</p>
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METHOD OF DIAGNOSIS OR TREATMENT OF NEUROLOGICAL DISORDERS WITH P75ECD AND/OR P75 (Fri, 30 Sep 2016)
A method of treating and/or preventing neurological conditions, comprising administering to a subject in need thereof a therapeutically effective amount of a p75 extracellular domain (p75ECD) or a functional fragment, variant, analogue or derivative thereof. Also provided is a method of diagnosing and/or prognosing Alzheimer's disease (AD) in a test subject comprising comparing the concentration of p75ECD and/or p75FL and/or the ratio of p75ECD: p75FL in a biological sample of the test subject to the concentration of p75ECD and/or p75FL and/or the ratio of p75ECD: p75FL in a comparable biological sample obtained from a non-demented control subject(s).
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DISUBSTITUTED PIPERIDINE DERIVATIVES AS BUTYRYLCHOLINESTERASE INHIBITORS FOR USE IN THE TREATMENT OF ALZHEIMER (Fri, 30 Sep 2016)
This invention relates to new inhibitors of butyrylcholinesterase with general formulas I and II, where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the treatment of Alzheimer's disease and other forms of dementia.
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HUMANIZED ANTIBODY (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease.</p>
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SPIROCYCLIC DIHYDRO-THIAZINE AND DIHYDRO-OXAZINE BACE INHIBITORS, AND COMPOSITIONS AND USES THEREOF (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">Compounds are provided having a structure according to Formula (I): wherein A<sub>1</sub>, A<sub>2</sub>, A<sub>3</sub>, Y, R<sub>1</sub>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, m, n and p are defined herein. Further provided are pharmaceutical compositions including the compounds provided and methods of making and using the compounds and compositions as provided, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.</p>
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">A compound of Formula I is provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.01mm" wi="56.98mm" file="US20160272628A1-20160922-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula I.</p>
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TAU IMAGING PROBE (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">An object of the present invention is to provide a probe for imaging a β-sheet structure protein which can be used for the diagnosis of conformational diseases, particularly disease (tauopathy) having a cardinal symptom such as intracerebral accumulation of tau protein, for example, Alzheimer's disease. Another object of the present invention is to provide a compound which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or non-recognized toxicity.</p> <p id="p-0002" num="0000">According to the present invention, the above problems are solved by providing a compound of a formula I (wherein A, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>a </sup>and R<sup>b </sup>are as defined in the present description) or a pharmaceutically acceptable salt or solvate thereof.</p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 23 Sep 2016)
Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu2), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also 10 relates to a process for manufacturing compounds of Formula I.
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ADENOSINE THIOPHOSPHATE DERIVATIVES AND USES THEREOF (Fri, 23 Sep 2016)
Novel adenosine 5'-thiophosphate derivatives, represented by Formulae (I) or (I*), and salts thereof, represented by Formulae (Ia) and (I*a), as defined in the specification, and uses thereof as antioxidants and/or P2Y1-R agonists, and/or in the treatment of medical conditions associated with oxidative stress and/or neurodegeneration, and in the treatment of Alzheimer's Disease in particular, are disclosed.
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CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula;</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="66.80mm" wi="76.03mm" file="US20160263257A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X is OH, C<sub>1</sub>-C<sub>6 </sub>alkoxyl; Y and Z are independently selected from a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxyl, halogen, mi-substituted or C<sub>1</sub>-C<sub>6 </sub>substituted amine, <sup>18</sup>F, <sup>19</sup>F, or H; and n is 1, 2, or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H and X is OH.</p>
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PHOSPHONATE DERIVATIVES AND METHODS OF USE THEREOF IN THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Benzothiazole phosphonate analogs and methods of using the same to inhibit the activity of Amyloid Binding Alcohol Dehydrogenase and in the amelioration or treatment of Alzheimer's disease are provided.</p>
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NOVEL 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">4-(Indol-3-yl)-pyrazole derivative compounds of Formula I or pharmaceutically acceptable enantiomers, salts or solvates thereof are provided. Further provided is the use of the compounds of Formula I as TDO2 inhibitors. Also provided herein is use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity.</p>
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C6-SPIRO IMINOTHIADIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): (structurally represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds, wherein R1, R2, R3, X, Y, s, ring A, RA, m, -L1-, and RL 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:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="57.15mm" file="US20160264538A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLIC COMPOUND (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">The problem of the present invention is to provide a compound having a PDE2A inhibitory action, and useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="69.93mm" file="US20160264536A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the DESCRIPTION, or a salt thereof.</p>
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ALZHEIMER'S DISEASE ASSAY IN A LIVING PATIENT (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">An assay for Alzheimer's disease pathology (AD) in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, TLR4-FLNA and/or α7nAChR-Aβ<sub>42 </sub>complex present as a protein-protein complex in a sample is determined and compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is determined and compared to an amount determined in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four of the six pharmacophores of FIGS. <b>7</b>-<b>12</b>. An amount of protein or protein complex determined in the presence of the medicament less than the first determined amount indicates a favorable treatment prognosis.</p>
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SYNTHESIS AND UTILITY OF NEW CAPGROUP LARGAZOLE ANALOGS (Fri, 16 Sep 2016)
Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.
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METHODS FOR TREATING PROTEINOPATHIES (Fri, 16 Sep 2016)
This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.
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THERAPEUTIC COMPOUNDS (Sat, 10 Sep 2016)
The invention provides compounds formula (I) and salts thereof: wherein R1-R4 have any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, inflammation, hyperresponsiveness, allergic conditions, asthma, and psychotic disorders such as schizophrenia. The compounds are also useful to lower IL-4, IL-5, or IL-15 levels in an animal.
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A PROCESS FOR THE PREPARATION OF A CAMSYLATE SALT ((1S)-(+)-10 CAMPHORSULFONIC ACID) OF (1R,1'R,4R)- 4-METHOXY-5"-METHYL-6'-[5-(PROP-1-YN-1-YL)PYRIDIN- 3-YL]-3'H-DISPIRO[CYCLOHEXANE-1,2'-INDEN-1'2'-IMIDAZOLE]-4"-AMINE (Thu, 08 Sep 2016)
A process for the preparation of a camsylate salt ((1S)-(+)-10 camphorsulfonic acid) of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine is disclosed as well as pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating A²-related pathologies such as Alzheimer's Disease, Down's Syndrome, ²-amyloid angiopathy and conditions such as dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's Disease, progressive supranuclear palsy or cortical basal degeneration.
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3,3-DISUBSTITUTED-(8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL)-THIOPHEN-3-YL]-METHANONES AS INHIBITORS OF 11 (BETA)-HSD1 (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.62mm" wi="57.23mm" file="US20160251346A1-20160901-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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AROMATIC HETEROCYCLIC COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Provided herein are novel aromatic heterocyclic compounds or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and methods for using such compounds or pharmaceutical compositions thereof to treat Alzheimer's disease.</p>
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Protective Effects of Oil Palm Composition on Alzheimer's Disease (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Present invention discloses an oil palm composition for use in prevention or treatment of Alzheimer's disease. The composition is useful in impeding formation of neurotoxic peptide. Present invention can be used in preparation of a medicament in a therapeutic effective amount for prevention or treatment of Alzheimer's disease and diseases related thereto.</p>
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CELLS EXPRESSING APOLIPOPROTEIN E AND USES THEREOF (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE-induced toxicity.</p>
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COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION (Fri, 02 Sep 2016)
The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation / retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.
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TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS (Fri, 02 Sep 2016)
The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound- 1, or a pharmaceutically acceptable salt thereof.
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HETEROCYCLIC COMPOUND (Thu, 01 Sep 2016)
The problem of the present invention is to provide a compound having a PDE2A inhibitory action, and useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.
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TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound-1, or a pharmaceutically acceptable salt thereof.</p>
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Imaging Beta-Amyloid Peptides Aggregation (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The present invention is in the field of pharmaceuticals and chemical industries. In particular, one aspect of the present invention relates to methods for labeling, imaging and detecting the beta-amyloid (Aβ) peptides, oligomers, and fibrils in vitro and in vivo via magnetic resonance and florescence imaging by using modified carbazole-based fluorophores. A further aspect of the present invention relates to a method of reducing and preventing aggregation of beta-amyloid peptides for Alzheimer's disease (AD) as well as of treating and/or preventing Alzheimer's disease by using the modified carbazole-based fluorophore. The modified carbazole-based fluorophore according to an embodiment of the present invention is prepared by conjugating a carbazole-based fluorophore with magnetic nanoparticles to form a conjugate which is permeable to blood brain barrier of a subject being introduced therewith.</p>
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URIDINE DIPHOSPHATE DERIVATIVES, PRODRUGS, COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISORDERS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">This disclosure relates to prodrugs of uridine diphosphate (UDP) derivatives, compositions comprising therapeutically effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma, and inflammatory conditions.</p>
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PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING DEGENERATIVE BRAIN DISEASE COMPRISING MULTI-TARGETING COMPOUNDS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">A pharmaceutical composition for treating or preventing a degenerative brain disease, the pharmaceutical composition including, as an active component, a multi-targeting compound for further improving treatment efficiency of a degenerative brain disease such as Alzheimer's disease is disclosed. The pharmaceutical composition includes a compound represented by Formula 1 or 2, wherein the compound of Formula 1 or 2 induces a gathering of amyloid-peptides in a manner of toxicity-free aggregation under conditions both in the presence and absence of metals such as copper and zinc, and also reacts with multiple targets of Alzheimer's diseases at once to inhibit toxicity thereof, the multiple targets including amyloid-peptide, metal-amyloid-peptide, a metal, and an activated oxidizing species. The pharmaceutical composition including the compound of Formula 1 or 2 may be utilized as a therapeutic agent or a health food in regard to a brain disease, including Alzheimer's disease.</p>
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Histamine-3 Receptor Antagonists (Fri, 19 Aug 2016)
<p id="p-0001" num="0000">The invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I; and a method of treatment of a disorder or condition selected from the list consisting of acute myocardial infarction; memory processes disorders; dementia; cognition disorders such as Alzheimer's disease; attention deficit disorder (ADD); attention-deficit hyperactivity disorder (ADHD); cancers such as cutaneous carcinoma, medullary thyroid carcinoma and melanoma; Meniere's disease; gastrointestinal disorders; inflammation; migraine; motion sickness; obesity; pain; septic shock; respiratory disorders (including allergic rhinitis, nasal congestion and allergic congestion) in a mammal, including a human, that may be effected by administering to said mammal a pharmacologically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.</p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 19 Aug 2016)
Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu3), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.
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OLIGOMER-SPECIFIC AMYLOID BETA EPITOPE AND ANTIBODIES (Thu, 18 Aug 2016)
An isolated antibody that specifically binds to a cyclic peptide comprising the conformational epitope which has at least the amino acid sequences GSNK or SNKG, wherein the K (lysine) is solvent-exposed and wherein the antibody can specifically bind to amyloid beta is described. Methods of treating and preventing Alzheimer's disease, as well as methods to produce the antibody, are also described.
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6-CYCLOALKYL-1, 5-DIHYDRO-PYRAZOLO [3, 4-D]PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A INHIBITORS (Thu, 11 Aug 2016)
Novel 6-Cycloalkyl-pyrazolopyrimidinones according to formula (I) with PDE9 inhibiting properties, wherein R 1 is a 5 or 6 membered aromatic heteroaryl-group, R 2 is an optional substituent, D is optionally substituted cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl or 2-, 3- or 4-pyridyl, m= 1 or 2 and n is 0, 1 or 2. The new compounds can be used as medicaments, in particular for the treatment of conditions concerning deficits in perception, concentration, learning or memory. Such conditions may be associated with Alzheimer's disease, schizophrenia and other diseases. The new compounds can be used in the treatment of cognitive impairment associated with such diseases.
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INDOLE DERIVATIVES AND PROCESS FOR THEIR PREPARATION (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">Substituted indole derivatives of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.59mm" wi="60.45mm" file="US20160220535A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein the radicals have e. g. the following meaning: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">R<sup>1 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl, R<sup>2 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl or cycloC<sub>3-12</sub>-alkyl;</li> <li id="ul0001-0002" num="0000">R<sup>3 </sup>is —OR</li> <li id="ul0001-0003" num="0000">R<sup>4 </sup>is hydrogen or halogen,</li> <li id="ul0001-0004" num="0000">R<sup>5 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl</li> <li id="ul0001-0005" num="0000">R<sup>6 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl</li> <li id="ul0001-0006" num="0000">R is hydrogen or —C<sub>1-6</sub>-alkyl;</li> <li id="ul0001-0007" num="0000">X is a group —C(O)CH<sub>2</sub>— or —CH═CH—;</li> <li id="ul0001-0008" num="0000">R<sup>7 </sup>is hydrogen <br/> are potent inhibitors of Abeta peptide polymerization and can be used for the treatment of e.g. Alzheimers disease or ocular disorders. </li> </ul> </p>
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C5-SPIRO IMINOTHIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">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</sup>, X, Y, R<sup>1A</sup>, R<sup>1B</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="59.86mm" file="US20160222032A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu<sub>2</sub>), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.</p>
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HETEROCYCLIC MOLECULES FOR BIOMEDICAL IMAGING AND THERAPEUTIC APPLICATIONS (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Probes which target diffuse and fibrillar forms of amyloid beta (Aβ) are described. These probes demonstrate high initial brain penetration and facile clearance from non-targeted regions. The agents can be used to image amyloid quantitatively for monitoring efficacy of Aβ-modifying therapeutics and assist in premortem diagnosis of Alzheimer's disease (AD). Disclosed probes can bind Aβ aggregates of preformed Aβ<sub>1-42 </sub>fibrils in vitro and can be used to image fibrillar and diffuse plaques ex vivo in brain sections. Disclosed probes can be used to determine Aβ burden in early stages of AD. These probes can be used for multimodality imaging of Aβ. F-AI-187(1 μM) can detect Aβ plaques in brain sections of APP/PS1 mice. F-AI-187(10 μM) can detect Aβ plaques in the frontal lobe in a brain section of a patient with confirmed AD. Some probes can be used for fluorescence imaging of plaque.</p>
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IMINOTHIADIAZINE DIOXIDES BEARING AN AMINE-LINKED SUBSTITUENT AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 29 Jul 2016)
In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, R2, ring A, RA, m, ring B, RB, and n 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.
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HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.</p>
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METHODS OF SYNTHESIZING y-AAPEPTIDES, y-AAPEPTIDE BUILDING BLOCKS, y-AAPEPTIDE LIBRARIES, AND y-AAPEPTIDE INHIBITORS OF Ab40 AGGREGATES (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">Embodiments of the present disclosure provide for γ-AApeptides, γ-AApeptide building blocks, methods of making γ-AApeptides and libraries of γ-AApeptides, methods of screening the γ-AApeptide libraries for desired peptidomimetic activity, and the like. The present disclosure also provides for γ-AApeptides that are inhibitors of Aβ peptide aggregation, methods of inhibiting and disassembling Aβ peptide aggregation, methods of inhibiting the toxicity of Aβ aggregates towards N2a neuroblasotma cells, as well as methods and compounds for treating Alzheimer's disease.</p>
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NEUROPROTECTIVE POLYPHENOL ANALOGS (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzheimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.</p>
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Anti-depression Compounds (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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3.ALPHA.-ETHYNYL, 3.BETA.-HYDROXY-5.ALPHA.-PREGNAN-20-OXIME FOR USE IN THE TREATMENT OF CNS DISORDERS (Fri, 22 Jul 2016)
The invention relates to 3α-ethynyl, 3β-hydroxy, 5α-pregnan-20-oxime or a pharmaceutically acceptable salt thereof, which compounds and/or salts are useful as modulators of the mammal brain excitability via the gamma-5 aminobutyric acid receptor-chloride ionophore (GABAA-R) complex and in the treatment of disorders such as hepatic encephalopathy, Down's syndrome and Alzheimer's disease.
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Compound or mixture of compounds for the treatment of neurodegenerative diseases or oxidative stress injuries (Thu, 21 Jul 2016)
A composition for the treatment and prevention of neurodegenerative disease and injuries induced by oxidative stress comprising coptisine or an extract from Coptis rhizome including pharmaceutically acceptable salts, tautomers and stereoisomers of the compound, including mixtures thereof in all ratios, is provided. Preferably the coptisine is combined with at least one further compound selected from the group including berberine, jatrorrhizine and palmitine including pharmaceutically acceptable salts, tautomers and stereoisomers of the compounds, including mixtures thereof in all ratios. The neurodegenerative disease may be selected from the group including Alzheimers disease and other dementias, brain cancer, degenerative nerve disease, encephaltitis, epilepsy, genetic brain disorders, head and brain malformations, hydrocephalus, stroke, Parkinsons disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease) Huntingtons disease and prion diseases. Coptisine or an extract from Coptis rhizome for modulating the activity of thioredoxine-interacting protein is also provided.
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NOVEL PI-EXTENDED ACEDAN DERIVATIVES, THEIR APPLICATION FOR TWO-PHOTON MICROSCOPY IMAGING, AND THEIR APPLICATION FOR TWO-PHOTON MICROSCOPY IMAGING OF AMYLOID-BETA PLAQUE IN AN ALZHEIMER'S DISEASE ANIMAL MODEL (Fri, 15 Jul 2016)
<p id="p-0001" num="0000">Provided are acedan derivatives having an extended π bond, a method for preparing the acedan derivatives, and a method for two-photon microscopy imaging of amyloid-beta plaque using the acedan derivatives; more particularly, to two-photon absorbing fluorescent compounds having a longer absorption wavelength and emission wavelength than acedan and acedan derivatives which are conventional two-photon absorbing fluorophores. The compounds provided may be usefully used for in vivo imaging studies by imaging cells or tissue using the compounds, and may also be usefully used for diagnosing Alzheimer's disease by imaging amyloid-beta plaque using the compounds.</p>
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.</p>
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GASTRIC RETENTIVE DOSAGE FORMS FOR EXTENDED RELEASE OF ACAMPROSATE INTO THE UPPER GASTROINTESTINAL TRACT (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Gastric retentive dosage forms for sustained release of acamprosate are described which may allow once- or twice-daily dosing for both acute and long-term treatment of a disorder including alcohol dependence, tinnitus, sleep apnea, Parkinson's disease, levodopa-induced dyskinesias in Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, Cortical spreading depression, migraine, schizophrenia, anxiety, tardive dyskinesia, spasticity, multiple sclerosis, various types pain, or binge eating. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.</p>
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SCREENING METHODS USING FYN IN COMBINATION WITH TAU PROTEIN (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The present invention provides materials and methods relating to screening for compounds useful in the treatment of Alzheimer's disease and related conditions. In particular, screening methods using tyrosine kinases are provided, as are methods relating to the role of tyrosine kinases as therapeutic targets.</p>
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Salt forms of [R-(R*,R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Novel salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid characterized by their X-ray powder diffraction pattern and solid-state NMR spectra are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.</p>
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Biological complex specific for Alzheimer's disease detection in vitro and use thereof (Wed, 29 Jun 2016)
<p id="p-0001" num="0000">A biomarker for Alzheimer's disease (AD) comprising a complex of an Aβ amyloid peptide and a cell or a cellular membrane. Non-invasive methods for diagnosing Alzheimer's disease or monitoring its development or progression using this biomarker.</p>
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NOVEL BIPHENYL DERIVATIVE AND METHOD FOR PREPARING SAME (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The present invention provides novel biphenyl derivatives, isomers thereof, or pharmaceutically acceptable salts thereof, methods for preparing the same, and a pharmaceutical composition containing the same. The novel biphenyl derivatives, isomers thereof, or pharmaceutically acceptable salts thereof, as disclosed in the present invention, act as muscarinic M3 receptor antagonists, and thus are useful for the prevention or treatment of a disease selected from the group consisting of chronic obstructive pulmonary disease, asthma, irritable bowel syndrome, urinary incontinence, rhinitis, spasmodic colitis, chronic cystitis, Alzheimer's disease, senile dementia, glaucoma, schizophrenia, gastroesophageal reflux disease, cardiac arrhythmia, and hyper-salivation syndromes.</p>
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MAGNESIUM COMPOSITIONS AND USES THEREOF FOR NEUROLOGICAL DISORDERS (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">A composition for administration to a subject, such as oral administration to a subject, for example, has been provided. Such a composition may comprise at least one magnesium-counter ion compound. A magnesium-counter ion composition described herein may be useful for any of a variety of applications provided herein, such as maintaining, enhancing, and/or improving health, nutrition, and/or another condition of a subject, and/or cognitive, learning, and/or memory function. A magnesium-counter ion composition provided herein may be useful for administration to a subject presenting magnesium deficiency, mild cognitive impairment, Alzheimer's disease, attention deficit hyperactivity disorder, ALS, Parkinson's disease, diabetes, migraine, anxiety disorder, mood disorder, and/or hypertension. A kit, method, and other associated technology are also provided.</p>
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GENETIC AND IMAGE BIOMARKETS ASSOCIATED WITH DECLINE IN COGNITIVE MEASURES AND BRAIN GLUCOSE METABOLISM IN POPULATIONS WITH ALZHEIMER'S DISEASE OR THOSE SUSCEPTIBLE TO DEVELOPING ALZHEIMER'S DISEASE (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">The present disclosure is based on the identification of biomarkers of combined genetic variants and imaging measurements, in predicting faster decline in cognitive measures and brain glucose metabolism in populations with Alzheimer's disease or those susceptible to developing Alzheimer's disease. The present disclosure provides a method of treating a patient with Alzheimer's disease (AD) or a subject susceptible to developing AD, comprising: (a) assaying a sample obtained from an early-stage AD patient or a subject susceptible to developing AD for the presence of a brain-derived neurotrophic factor (BDNF) gene mutation and/or a protein tyrosine phosphatase receptor-type, Z polypeptide 1 (Ptprz1) gene mutation; (b) determining whether the patient or subject is positive for brain amyloid-beta (Aβ), wherein the presence of brain Aβ in combination with the BDNF gene and/or Ptprz1 gene mutation correlates with a prediction of rapid cognitive decline; and (c) treating the patient or subject with early and aggressive therapy appropriate to treat AD with rapid cognitive decline.</p>
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2,3,4,5-TETRAHYDROPYRIDIN-6-AMINE AND 3,4-DIHYDRO-2H-PYRROL-5-AMINE COMPOUND INHIBITORS OF BETA-SECRETASE (Fri, 24 Jun 2016)
The present invention relates to 2,3,4,5-tetrahydropyridin-6-amine and 3,4- dihydro-2H-pyrrol-5-amine compound inhibitors of beta-secretase having the structure shown in Formula (I), wherein the radicals are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia associated with beta- amyloid, age-related macular degeneration, type 2 diabetes or metabolic disorders.
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3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOIC ACID USEFUL AS KYNURENINE MONOOXYGENASE INHIBITORS (Fri, 24 Jun 2016)
Compound of formula (I) wherein R1 is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl; and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disewase, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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PYRIDAZINE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Thu, 23 Jun 2016)
This invention relates to pyridazine derivatives, compositions comprising therapeutically effective amounts of those pyridazine derivatives and methods of using those derivatives or compositions in treating central nervous system (CNS) disorders with cognitive impairment that are responsive to agonists of ±5 subunit containing GABA A receptor, e.g. , age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease(AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia and cancer-therapy-related cognitive impairment.
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HUMANIZED ANTIBODY IGG1 (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease.</p>
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INHIBITORS OF HUMAN 12/15-LIPOXYGENASE (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.</p>
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GLYCINE TRANSPORTER INHIBITOR (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds of formula [I] or pharmaceutically acceptable salts thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.25mm" wi="76.28mm" file="US20160159814A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.</p>
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HETEROCYCLIC COMPOUND (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">A compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="69.93mm" file="US20160159808A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the SPECIFICATION, or a salt thereof has a PDE2A inhibitory action, and is useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like.</p>
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Pyrroloquinoline Derivatives as 5-HT6 Antagonists, Preparation Method and Use Thereof (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">This invention concerns pyrroloquinoline derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome. The compounds have the general formula (XIV), wherein the symbols have the meanings given in the description.</p>
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Quinoline Carboxamide and Quinoline Carbonitrile Derivatives as mGluR2-Negative Allosteric Modulators, Compositions, and Their Use (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.17mm" wi="58.34mm" file="US20160159744A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein ring A, R<sup>Q</sup>, -L-, R<sup>1</sup>, n, R<sup>2</sup>, and R<sup>3 </sup>are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, including potentially Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.</li> </ul> </li> </ul> </p>
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Amino-Oxazine and Amino-Dihydrothiazine Compounds as Beta-Secretase Modulators and Methods of Use (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">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</sup>, A<sup>2</sup>, A<sup>3</sup>, A<sup>3</sup>, A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, L, R<sup>2</sup>, R<sup>7</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="62.91mm" file="US20160159818A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS OF TREATMENT FOR ALZHEIMER'S DISEASE AND HUNTINGTON'S DISEASE (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">This invention relates generally to methods of treatment for neurodegenerative diseases such as Alzheimer's disease, Alzheimer's-related diseases, and Huntington's disease, and more specifically to methods involving the inhibition of the classical pathway of complement activation.</p>
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IGF-1R SIGNALING PATHWAY INHIBITORS USEFUL IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention provides compounds acting as Insulin/IGF signaling modulators useful in the treatment of neurodegenerative diseases and disorders. The invention provides pharmaceutical compositions including such compounds, and methods of using these compounds and compositions for the treatment of neurodegenerative diseases, in particular neurodegenerative diseases caused by proteotoxicity such as Alzheimer's disease.</p>
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Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.</p>
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Quinoline Carboxamide and Quinoline Carbonitrile Derivatives as mGluR2-Negative Allosteric Modulators, Compositions, and Their Use (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.33mm" wi="58.59mm" file="US20160158217A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein ring A, R<sup>Q</sup>, -L-, R<sup>1</sup>, n, R<sup>2</sup>, and R<sup>3 </sup>are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, including potentially Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.</li> </ul> </li> </ul> </p>
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Compounds for treatment of alzheimer's disease (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The invention is directed to the use of a compound of formula I, as defined herein, to a pharmaceutically acceptable salt thereof; to a pharmaceutical composition containing a compound of formula I, and to a combination of a compound of formula I with a pharmacologically effective cholinesterase inhibitor to treat a mammal, including a human, for a disorder or condition selected from the list including Alzheimer's disease, Huntington's disease, Parkinson's disease, non-Alzheimer's dementias and ALS.</p>
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NOVEL BIPHENYL DERIVATIVE AND METHOD FOR PREPARING SAME (Thu, 09 Jun 2016)
The present invention provides novel biphenyl derivatives, isomers thereof, or pharmaceutically acceptable salts thereof, methods for preparing the same, and a pharmaceutical composition containing the same. The novel biphenyl derivatives, isomers thereof, or pharmaceutically acceptable salts thereof, as disclosed in the present invention, act as muscarinic M3 receptor antagonists, and thus are useful for the prevention or treatment of a disease selected from the group consisting of chronic obstructive pulmonary disease, asthma, irritable bowel syndrome, urinary incontinence, rhinitis, spasmodic colitis, chronic cystitis, Alzheimer's disease, senile dementia, glaucoma, schizophrenia, gastroesophageal reflux disease, cardiac arrhythmia, and hyper-salivation syndromes.
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Thu, 09 Jun 2016)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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EphA4 INHIBITORS AS NEUROPROTECTIVE AGENTS (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">Provided is the discovery of the role of EphA4 signaling in neurodegenerative disorders involving β-amyloid induced neurotoxicity such as Alzheimer's Disease. New therapeutic methods, therapeutic agents, and kits for treating diseases caused or exacerbated by overactivated EphA4 signaling are provided. Also provided are methods for identifying additional compounds as therapeutic agents useful for treating conditions involving overly active EphA4 signaling.</p>
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SUBSTITUTED BENZAMIDE DERIVATIVES AS IN VITRO MAO-B INHIBITORS (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The invention relates to the use of substituted benzamide derivatives of Formula I: Wherein: A<sup>1 </sup>and A<sup>2 </sup>are —N or —CH, so that if A<sup>1 </sup>is —N, then A<sup>2 </sup>is —CH and If A<sup>2 </sup>is —N, then A<sup>1 </sup>is —CH; R is a hydrogen atom, or represents branched or unbranched —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), —(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen, or R is a group wherein R<sup>3 </sup>and R<sup>4 </sup>both together or independently are halogen, hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, —O—((C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), —O—(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen; R<sup>1 </sup>and R<sup>2 </sup>both together or independently are halogen, hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —(C<sub>1</sub>-C<sub>3</sub>C)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, —O—(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), -0-(C<sub>1</sub>C<sub>3</sub>)—O—(C<sub>1</sub>C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen, their pharmaceutically acceptable salts, isomers or mixtures thereof as in vitro selective MAO-B inhibitors. The substituted benzamide derivatives of Formula I, their pharmaceutically acceptable salts, isomers or mixtures thereof are useful for the manufacture of a medicament for prevention and treatment of acute and chronic neurological disorders, cognitive and neurodegenerative diseases, more precisely for the manufacture of a medicament for prevention and treatment of neurodegenerative disorders such as Parkinson's Disease and Alzheimer's Disease.</p>
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5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid.</p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.66mm" wi="53.68mm" file="US09518042-20161213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="69.85mm" file="US09499516-20161122-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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PPAR-sparing compounds for the treatment of metabolic diseases (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to hydroxamate compounds and pharmaceutical compositions that are useful for treating and/or preventing metabolic inflammation mediated diseases such as diabetes, obesity, hypertension, dyslipidemia, a neurodegenerative disorder (e.g., Alzheimer's disease, Parkinson's disease, or Huntington's disease), or any combination thereof. Moreover, the present invention also provides methods of treatment for these diseases or disorders.</p>
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C5-C6-OXACYCLIC FUSED IMINOPYRIMIDINONE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 03 Jun 2016)
In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminopyrimidinone compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein RN, R1, RA, ring A, m, n, -L1-, ring B, RB, and p 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.
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GLYCINE TRANSPORTER INHIBITOR (Thu, 02 Jun 2016)
The present invention provides novel compounds of formula [I] or pharmaceutically acceptable salts thereof: which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.
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HETEROCYCLIC COMPOUND (Thu, 02 Jun 2016)
A compound represented by the formula (I): wherein each symbol is as described in the SPECIFICATION, or a salt thereof has a PDE2A inhibitory action, and is useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like.
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ALXR AGONIST COMPOUND (Fri, 27 May 2016)
<p id="p-0001" num="0000">The present invention provides a compound having ALXR agonist activity. Specifically, the invention provides a compound having ALXR agonist activity represented by general formula (I) wherein all the symbols are as defined in the specification, a salt thereof, a solvate thereof, or a prodrug thereof as well as an agent containing the same as an active ingredient for preventing and/or treating an ALXR-associated disease, such as an inflammatory bowel disease, an autoimmune disease, a chronic inflammatory disease, asthma, pulmonary fibrosis, atopic dermatitis, ischemia-reperfusion injury, myocardial infarction, or Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.73mm" wi="71.20mm" file="US20160145249A1-20160526-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2 -AMINO-4 - (PYRIDIN- 2 -YL) - 5, 6 -DIHYDRO-4H- 1, 3 -OXAZINE DERIVATIVES AND THEIR USE AS BACE-1 AND/OR BACE - 2 INHIBITORS (Thu, 26 May 2016)
The invention relates to novel oxazine derivatives of formula (I), and pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, combinations thereof, and their use as medicaments, particularly for the treatment of Alzheimer's Disease via inhibition of BACE-1.
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Pyrrole derivatives as alpha 7 nAChR modulators (Fri, 20 May 2016)
<p id="p-0001" num="0000">Disclosed are compounds of the formula (I), wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7 </sup>and m are as described herein, as modulators of the nicotinic acetylcholine receptors, particularly the α7 subtype, their tautomeric forms, stereoisomers, and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, and combinations thereof with suitable other medicaments. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and/or treatment of disorders such as Alzheimer's disease, mild cognitive impairment, and senile dementia.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.69mm" wi="57.49mm" file="US09504680-20161129-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2-AMINO-5,5-DIFLUORO-6-(FLUOROMETHYL)-6-PHENYL-3,4,5,6-TETRAHYDROPYRIDINES AS BACE1 INHIBITORS (Fri, 20 May 2016)
The present invention is directed to compounds of Formula (I) which are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Αβ deposits is beneficial such as Alzheimer's disease.
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2-AMINO-3,5-DIFLUORO-3,6-DIMETHYL-6-PHENYL-3,4,5,6-TETRAHYDROPYRIDINES AS BACE1 INHIBITORS FOR TREATING ALZHEIMER'S DISEASE (Fri, 20 May 2016)
The present invention is directed to compounds according to Formula (I) which compounds are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for 5 which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.
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2-AMINO-6-(DIFLUOROMETHYL)- 5,5-DIFLUORO-6-PHENYL-3,4,5,6-TETRAHYDROPYRIDINES AS BACE1 INHIBITORS (Fri, 20 May 2016)
The present invention is directed to compounds of formula (I) which are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Αβ deposits is beneficial such as Alzheimer's disease.
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METHODS FOR TREATING NEURODEGENERATIVE DISEASES (Fri, 20 May 2016)
Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models. The present disclosure shows that age dependent accumulation of genomic lesions leads to the production of RNA molecules within neurons that mimic viruses and intrinsically activate innate immune signaling, which triggers neurodegeneration. This hypothesis is supported by the results shown herein elucidating the mechanism of neurodegeneration in two mouse lines that specifically express different isoforms of the human amyloid precursor protein (hAPP) gene, which is associated with Alzheimer's disease (AD), exclusively in olfactory sensory neurons (OSNs) in the nose.
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SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOFAND METHODS FOR THE PRODUCTION AND USE THEREOF (Thu, 19 May 2016)
The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT 6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT 6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity. In the general formula 1: wherein: X = S, SO or NH; R 1 represents hydrogen, optionally substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R 2 represents hydrogen, halogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R 3 represents hydrogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X = S or X = NH, at least one of R 1 , R 2 or R 3 represent substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R 1 , R 2 or R 3 represent hydrogen; R 4 represents C 1 -C 3 alkyl; R 5 represents hydrogen, one or two halogens, C 1 -C 3 alkyl or optionally substituted hydroxyl.
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2-Amino-6-(difluoromethyl)-5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 Inhibitors (Fri, 13 May 2016)
<p id="p-0001" num="0000">The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.</p>
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Indazole inhibitors of the Wnt signal pathway and therapeutic uses thereof (Fri, 13 May 2016)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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POTENT GAMMA-SECRETASE MODULATORS (Sat, 07 May 2016)
Provided herein are compounds and methods for treating a disorder associated with aberrant A3 peptide levels, including Alzheimer's disease. Provided herein are compositions and methods for treating a disorder associated with aberrant AP peptide levels, including AD. Provided herein are compounds of Formula (A) or a pharmaceutically acceptable salt thereof, wherein, L' is selected from the group consisting of C(O), C(R1)(R2), substituted or unsubstituted -C2-6 alkylene-, and substituted or unsubstituted -C3-6 cycloalkylene.
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SALTS OF VALPROIC ACID WITH PIPERAZINE, ETHYLENEDIAMINE, LYSINE AND/OR EICOSAPENTAENOIC ECID (EPA) AMINE DERIVATIVES FOR THE TREATMENT OF EPILEPSY (Sat, 07 May 2016)
The compositions and compounds of formula I, formula II, formula III and formula IV which includes a salt of valproic acid or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula III and formula IV and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, migraine, schizophrenia, depression, Alzheimer's disease, cancer, HIV and familial adenomatous polyposis.
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CONJUGATES OF POLYUNSATURATED FATTY ACIDS AND AMINE-CONTAINING COMPOUNDS AND USES THEREOF (Fri, 06 May 2016)
<p id="p-0001" num="0000">Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases, dermatitis and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis.</p>
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GHRELIN SPLICE VARIANT FOR TREATING NEURONAL DAMAGE,NEURODEGENERATIVE DISEASE, PARKINSONS DISEASE, ALZHEIMERS DISEASE, AND/OR DEPRESSION (Fri, 06 May 2016)
<p id="p-0001" num="0000">The present disclosure relates, in one aspect, to use of ghrelin splice variant or an analogue thereof, or a ghrelin splice variant-like compound for the preparation of a medicament for one or more of: treatment and/or prevention of neuronal damage and/or neurodegeneration and, prophylaxis or treatment of neuronal damage and/or neurodegenerative disease, Parkinson's disease, Alzheimer's disease, depression stimulation of neuronal activity. A further aspect relates to a number of new ghrelin splice variant-like compounds and uses thereof, as well as to pharmaceutical compositions and medical packaging comprising the new ghrelin splice variant-like compounds.</p>
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS (Fri, 06 May 2016)
<p id="p-0001" num="0000">The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing neurological disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, migraine, schizophrenia, depression, Alzheimer's disease, cancer, HIV and familial adenomatous polyposis.</p>
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4-AMINO-6-PHENYL-5,6-DIHYDROIMIDAZO[1,5-A]PYRAZINE DERIVATIVES AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazinyl derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.</p>
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4-AMINO-6-PHENYL-5,6-DIHYDROIMIDAZO[1,5-A]PYRAZIN-3(2H)-ONE DERIVATIVES AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazin-3(2H)-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.</p>
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DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF (Fri, 29 Apr 2016)
Provided herein are compounds of formula (I) and compositions containing the compounds. The compounds and compositions are useful in the methods of treating, amelioration or prophylaxix of diseases associated with Nrf2/ NF-κΒ pathways. The diseases associated include, but are not limited to a fibrotic disease such as lung fibrosis, liver fibrosis, kidney fibrosis, and scleroderma, or a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, and sickle cell disease.
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POLYPRENYLATED PHLOROGLUCINOL COMPOUNDS AS POTENT P-GLYCOPROTEIN INDUCERS (Fri, 29 Apr 2016)
The present invention relates to the polyprenylated phloroglucinol compounds of formulae I and II. The present invention also provides synthesis and p-glycoprotein induction activity of the alkyl- and acyl- polyprenylated phloroglucinol compounds. Further, use of the compounds as p-glycoprotein inducers and methods of treatment of Alzheimer's disease using compounds of the invention are also provided.
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ALKYLIDENE PHOSPHONATE ESTERS AS P-GLYCOPROTEIN INDUCERS (Fri, 29 Apr 2016)
The present invention relates to the alkylidene phosphonate esters of formula I wherein, R1 is selected from a group consisting of hydrogen or alkyl group; R2 is selected from a group consisting of hydrogen, hydroxy, alkyl, alkoxy, nitro, halogen, amino, N- substituted alkylamino; alkyl group is selected from a group consisting of methyl, ethyl and isopropyl; Ar is selected from a group consisting of aryl, substituted aryl, fused aryl, heteroaryl, and substituted heteroaryl. The present invention particularly relates to synthesis and p-glycoprotein induction activity of the alkylidene phosphonate esters. In addition, the invention relates to methods of using compounds for treating or preventing Alzheimer's disease.
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N-SUBSTITUTED BETA-CARBOLINIUM COMPOUNDS AS POTENT P-GLYCOPROTEIN INDUCERS (Fri, 29 Apr 2016)
The present invention relates to the N-substituted beta-carbolinium compounds of general formula A and formulae I and II wherein, R1 and R2 groups are selected from halogens or trifluoromethyl; R3 group is selected from hydrogen or methyl; Ar is selected from aryl and heteroaryl, X is selected from halogens; and R1 and R2 groups may be attached to any position on ring E. The present invention particularly relates to synthesis and p-glycoprotein induction activity of the N-substituted beta-carbolinium compounds. In addition, the invention relates to methods of using compounds for treating or preventing Alzheimer's disease.
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CYCLIZED TRANSTHYRETIN PEPTIDE AND METHODS OF USE THEREFOR (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present disclosure describes cyclized peptides that inhibit Aβ toxicity and therefore can be used as therapeutic agents to treat Alzheimer's Disease.</p>
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4-(5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)-1,4-dimethyl-1H-pyrrol-3-yl)benzenesulfonamide as alpha 7 nAChR modulator (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">Disclosed are an alpha 7 nAChR receptor modulator compound, 4-(5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)-1,4-dimethyl-1H-pyrrol-3-yljbenzenesulfonamide, its tautomeric form, its pharmaceutically acceptable salts, pharmaceutical compositions comprising the compound or a salt thereof, and a method of treating various diseases, disorders or conditions, for example, Alzheimer's disease, mild cognitive impairment, senile dementia, vascular dementia, dementia of Parkinson's disease, and attention deficit disorder.</p>
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GLYCINE TRANSPORTER INHIBITOR (Thu, 21 Apr 2016)
The present invention provides novel compounds of formula [IA] or pharmaceutically acceptable salts thereof: which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.
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PROGRANULIN FOR USE IN TREATING PARKINSON'S DISEASE OR ALZHEIMER'S DISEASE (Thu, 21 Apr 2016)
The invention relates to methods and compositions for treating a neurodegenerative disease. More particularly, the present invention is directed to methods of treatment of neurodegenerative diseases using progranulin and progranulin polypeptides, and methods of treatment of neurodegenerative diseases using effectors, or combinations of effectors, that modify progranulin expression.
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CRYSTALLINE FORMS OF [R-(R*,R*)]-2-(4-FLUOROPHENYL)-BETA, DELTA-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID CALCIUM SALT (2:1) (ATORVASTATIN) (Thu, 21 Apr 2016)
Novel crystalline forms of [R-(R*,R*)]-2-(4-fluorophenyl)-², ”;-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt atorvastatin designated Form V, Form VI, Form VII, Form VIII, Form IX, Form X, Form XI, Form XII, Form XIII, Form XIV, Form XV, Form XVI, Form XVII, Form XVIII, and Form XIX are characterized by their X-ray powder diffraction, solid-state NMR, and/or Raman spectroscopy are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, and Alzheimer's disease.
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BACE1 inhibitors (Fri, 15 Apr 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p>
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 15 Apr 2016)
The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
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INHIBITORS OF LYSINE GINGIPAIN (Fri, 15 Apr 2016)
The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimers disease. In certain embodiments, the invention provides compounds according to Formula (I), as described herein, and pharmaceutically acceptable salts thereof.
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MRI IMAGING OF AMYLOID PLAQUE USING LIPOSOMES (Fri, 15 Apr 2016)
Provided are aromatic compounds, phospholipid-polymer-aromatic conjugates comprising the aromatic compounds, and liposome compositions including the phospholipid- polymer-aromatic conjugates. The liposomal compositions may be useful for imaging of Alzheimer's Disease, for example, imaging of the amyloid-β plaque deposits characteristic of Alzheimer's Disease.
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BACE1 INHIBITORS (Fri, 15 Apr 2016)
The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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Indole derivatives and process for their preparation (Wed, 13 Apr 2016)
<p id="p-0001" num="0000">Substituted indole derivatives of formula (I) wherein the radicals have e. g. the following meaning: R<sup>1 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl, R<sup>2 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl or cycloC<sub>3-12</sub>-alkyl; R<sup>3 </sup>is OR R<sup>4 </sup>is hydrogen or halogen, R<sup>5 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl R<sup>6 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl R is hydrogen or —C<sub>1-6</sub>-alkyl; X is a group —C(O)CH<sub>2</sub>— or —CH═CH—; R<sup>7 </sup>is hydrogen are potent inhibitors of Abeta peptide polymerization and can be used for the treatment of e.g. Alzheimers disease or ocular disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.58mm" wi="60.71mm" file="US09309196-20160412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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LABELLED CARBOXYLIC ACIDS AND THEIR USES IN MOLECULAR IMAGING (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of imaging compounds, and more specifically to certain 2,2-dialkyl radionuclide-labelled carboxylic acids suitable for PEWT, SPECT and/or DNP imaging. Also described are uses of such compounds in the imaging of, inter alia, cancer tumors, metastasis, Alzheimer's disease and multiple sclerosis.</p>
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INHIBITORS OF LYSINE GINGIPAIN (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">The present invention relates generally to therapeutics targeting the bacterium <i>Porphyromonas gingivalis</i>, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with <i>P. gingivalis </i>infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.31mm" wi="69.85mm" file="US20160096830A1-20160407-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHENYLPYRROLE DERIVATIVE (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">Provided are novel compounds that are useful in the prevention or treatment of such diseases as dementia, Alzheimer's disease, attention-deficient hyperactivity disorder, schizophrenia, epilepsy, central convulsion, obesity, diabetes mellitus, hyperlipidemia, narcolepsy, idiopathic hypersomnia, behaviorally induced insufficient sleep syndrome, sleep apnea syndrome, circadian rhythm disorder, parasomnia, sleep related movement disorder, insomnia, and depression, or allergic rhinitis, or pharmaceutically acceptable salts of such compounds. Specifically, there are provided phenylpyrrole compounds represented by the following formula (I) or pharmaceutically acceptable salts thereof:</p> <p id="p-0002" num="0000">Formula (I)</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.07mm" wi="76.20mm" file="US20160095848A1-20160407-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">[wherein Q refers to a group represented by the following formula (A) or (B):</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="60.45mm" wi="76.20mm" file="US20160095848A1-20160407-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INDOLIN-2-ONE OR PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE DERIVATIVES (Fri, 08 Apr 2016)
<p id="p-0001" num="0000">The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.45mm" wi="69.85mm" file="US20160095844A1-20160407-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Ar is a 6-membered heteroaryl group, containing one or two N-atoms, which are the groups, pyridinyl, pyrimidinyl, pyridazinyl, or a 5-membered heteroaryl group containing from 1 to 3 heteroatoms, selected from N, S or O, which groups are imidazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadazolyl, isoxazolyl, oxazolyl, 1,3,4-thiadiazolyl or pyrazolyl;</li> </ul> </li> <li id="ul0001-0002" num="0000">R<sup>1 </sup>is hydrogen, lower alkyl, halogen, amino, dimethylamino, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, CH(OH)CF<sub>3</sub>, (CH<sub>2</sub>)<sub>o</sub>-lower alkoxy, cycloalkyl optionally substituted by CF<sub>3</sub>, or heterocycloalkyl optionally substituted by lower alkyl;</li> <li id="ul0001-0003" num="0000">R<sup>2 </sup>is hydrogen, lower alkyl, (CH<sub>2</sub>)<sub>o</sub>-cycloalkyl, (CH<sub>2</sub>)<sub>o</sub>—O-cycloalkyl, (CH<sub>2</sub>)<sub>o</sub>-lower alkoxy, CH<sub>2</sub>)<sub>o</sub>-lower alkoxy substituted by halogen, (CH<sub>2</sub>)<sub>o</sub>-heterocycloalkyl optionally substituted by lower alkyl, (CH<sub>2</sub>)<sub>o</sub>—S(O)<sub>2</sub>-cycloalkyl, lower alkyl substituted by one or two hydroxy, lower alkyl substituted by one or two lower alkoxy, (CH<sub>2</sub>)<sub>o</sub>—S(O)<sub>2</sub>-lower alkyl, lower alkyl substituted by halogen or CH<sub>2</sub>CH(OH)CF<sub>3</sub>;</li> <li id="ul0001-0004" num="0000">R<sup>3 </sup>is halogen or lower alkyl;</li> <li id="ul0001-0005" num="0000">X is CH or N;</li> <li id="ul0001-0006" num="0000">X<sup>1 </sup>is CH or N;</li> <li id="ul0001-0007" num="0000">n is 1 or 2;</li> <li id="ul0001-0008" num="0000">is 0, 1, 2 or 3;</li> <li id="ul0001-0009" num="0000">m is 0, 1 or 2;</li> <li id="ul0001-0010" num="0000">and the dotted line indicates a bond may or may not be present; or,</li> <li id="ul0001-0011" num="0000">a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof</li> </ul> </p> <p id="p-0004" num="0000">The compounds may be used for the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.</p>
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SPHINGOSINE KINASE INHIBITORS (Fri, 08 Apr 2016)
Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both. Certain compounds are selective for sphingosine kinase type 2 relative to sphingosine kinase type 1. Compounds of the invention can be used in treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. Diseases that can be treated by administration of an effective dose of a compound of the invention include a neoplastic disease that involves excess vascular growth; macular degeneration or diabetic retinopathy; an allergic disease such as asthma, an inflammatory disease of the eye such as uveitis, scleritis, or vitritis; an inflammatory disease of the kidney; a fibrotic disease; atherosclerosis; or pulmonary arterial hypertension. A compound of the invention can be used to improve the integrity of a vascular barrier in a disease where the vascular barrier is disrupted, such as cancer or Alzheimer's disease.
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C5-C6-FUSED TRICYCLIC IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 08 Apr 2016)
In its many embodiments, the present invention provides certain C5-C6 fused tricyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R2, R3, RA, ring A, RA, m, -L1-, and RL 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.
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METHODS FOR THE TREATMENT OF NEURODEGENERATION (Fri, 01 Apr 2016)
<p id="p-0001" num="0000">The invention encompasses the discovery that Fc-containing polypeptides that include branched glycans and that are sialylated on the branched glycan (e.g., on an α 1,3 and/or α 1,6 arm in the Fc region's N-linked glycosylation site), with, e.g., a NeuAc-α 2,6-Gal or NeuAc-α 2,3-Gal terminal linkage, are useful in treating neurodegeneration, e.g., in the treatment of neurodegenerative diseases such as Alzheimer's Disease. The present disclosure provides, in part, methods for treating neurodegeneration or neurodegenerative diseases by administering compositions containing such Fc-containing polypeptides as well as methods for evaluating, identifying, and/or producing (e.g., manufacturing) such polypeptides for the treatment of neurodegeneration.</p>
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PRODRUG OF 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE (Fri, 25 Mar 2016)
<p id="p-0001" num="0000">The present invention relates to the compound (2R,2′R)-bis(((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl) 1,1′-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.</p>
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DIAZINE-FUSED AMIDINE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 25 Mar 2016)
In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R1B, R2, RA, ring A, RA, m, L1, RL, ring C, RC, and p 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.
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MACROCYCLIC LRRK2 KINASE INHIBITORS (Fri, 25 Mar 2016)
The present invention relates to novel macrocyclic compounds of formula (I) and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 (Leucine-Rich Repeat Kinase 2). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine or diagnostic agent, in particular for the treatment and/or diagnosis of diseases characterized by LRRK2 kinase activity such as neurological disorders including Parkinson's disease and Alzheimer's disease.
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Naphthyl sulfonamide derivatives as KEAP-1 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders (Thu, 24 Mar 2016)
The present invention relates to naphthyl sulfonamide derivatives of the formula I in which R1, R2, R3, R4, R5, R6, R10, A, D, X, q, i, n, L and R50 are defined as indicated below. The naphthyl sulfonamide derivatives I are KEAP-1 modulators and useful for the prevention and/or treatment of diabetes, obesity, dyslipidemia and related disorders, neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. The invention furthermore relates to the use of naphthyl sulfonamide derivatives of the formula I or II as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.
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Compositions and methods for the treatment of epilepsy (Wed, 23 Mar 2016)
<p id="p-0001" num="0000">The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder, partial seizures, adjunctive therapy for partial, myoclonic, tonic-clonic seizures and schizophrenia, neuropathic pain, seizures, Tourette syndrome, Alzheimer's disease, autism, bipolar disorder and anxiety disorder, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, myotonia congenita and post-traumatic stress disorder.</p>
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A PRODRUG OF 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The present invention relates to the compound (2R,2′R)-bis(((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl) 1,1′-adipoylbis(pyrrolidine-2-carboxylate) of formula (I), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="57.49mm" wi="75.95mm" file="US20160075694A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3, 4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.</p>
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AMYLOID PRECURSOR PROTEIN MRNA BLOCKERS FOR TREATING DOWN SYDNROME AND ALZHEIMER'S DISEASE (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The present disclosure relates to methods for treating a neurodegenerative disorder by administering an effective amount of an agent that inhibits or reduces translation of amyloid precursor protein. In some embodiments, the neurodegenerative disorder is Alzheimer's disease or Down syndrome. Also disclosed are methods for decreasing amyloid-beta production in a subject's brain. Further disclosed is a method for restoring or maintaining iron homeostasis in a subject's brain.</p>
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NOVEL HETEROCYCLE COMPOUNDS AND USES THEREOF (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula (Q) or (1), Which penetrate the blood-brain barrier, inhibit the formation and accumulation of beta-amyloid, and are useful in the treatment of neurodegenerative diseases, particularly Alzheimer's disease. Further, the compounds of the present invention inhibit certain kinases, thereby being useful for the treatment of cancers of the central nervous system.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="59.10mm" wi="69.85mm" file="US20160075683A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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URIDINE NUCLEOSIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">This disclosure relates to uridine nucleoside derivatives, compositions comprising therapeutically effective amounts of those nucleoside derivatives and methods of using those nucleoside derivatives or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma and inflammatory conditions.</p>
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QUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">The present invention is directed to quinoline amide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositious comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.32mm" wi="64.69mm" file="US20160075656A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Pro-neurogenic compounds (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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S-IMINO-S-OXO IMINOTHIAZINE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 18 Mar 2016)
In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R1B, R2A, R2B, R2, R3, RN, ring A, RA, m, ring B, RB, and n 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.
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AMINOMETHYL- AND METHYLOXY-LINKED TRICYCLIC COMPOUNDS AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 18 Mar 2016)
The present invention relates to certain aminomethyl- and methyloxy-linked tricyclic compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy.
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CELLS EXPRESSING APOLIPOPROTEIN E AND USES THEREOF (Fri, 18 Mar 2016)
Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE- induced toxicity.
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Cycloalkyl-diamines for CNS disorders (Wed, 16 Mar 2016)
<p id="p-0001" num="0000">The invention is directed to the use of a compound of formula I as defined herein, a pharmaceutically acceptable salt thereof; or a pharmaceutical composition containing a compound of formula I, in treating a mammal, including a human, for a psychiatric disorder or condition selected from the group consisting of depression, mood disorders, anxiety, schizophrenia, bipolar disorder (also referred to as manic-depressive disorder), addiction, cognitive impairment, Parkinson's and Alzheimer's diseases.</p>
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COMPOSITIONS AND METHODS FOR TREATING BETA-AMYLOID RELATED DISEASES (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">In alternative embodiments the invention provides compositions and methods for ameliorating diseases and conditions having a beta-amyloid component, including Alzheimer's disease (AD), Vascular Dementia (VD), dementia, pre-dementia, Cognitive Dysfunction Syndrome (CDS) and loss of cognition in humans and in non-human animal. In alternative embodiment the invention provides analogs of AB-007 and its acid form E64c (loxistatin), their preparation, and pharmaceutical compositions thereof and methods of making and using same. In alternative embodiments compositions of the invention are deuterated analogs of AB-007 (or E64d) and E64c (or loxistatin). In alternative embodiments compositions of the invention are metabolically blocked forms as compared to AB-007 and loxistatin. In alternative embodiments compositions of the invention are used to ameliorate (including treat, slow, reverse or prevent) a disease or condition which can be ameliorated by partial or complete inhibition of a cysteine protease, e.g., AD, VD, CDS. The invention also provides alternative dosage forms and formulations for AB-007 and loxistatin, and for compounds of this invention, which can be used e.g., to treat AD, VD and CDS, in humans and in non-human animals.</p>
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.</p>
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TETRAHYDRONAPHTHYRIDINE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 04 Mar 2016)
Provided are quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1, R 2, L, X 1, X 2, and X 3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.
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TETRAHYDRONAPHTHYRIDINE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 04 Mar 2016)
The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, L, X1, X2, and X3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.
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GLYCOSIDASE INHIBITORS (Fri, 04 Mar 2016)
Compounds of formula (I) wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
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3, 7-DIAMINO-10H-PHENOTHIAZINE SALTS AND THEIR USE (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.28mm" wi="66.55mm" file="US20160051559A1-20160225-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein: R<sup>1 </sup>and R<sup>9 </sup>are independently selected from: —H; C<sub>1-4</sub>alkyl; C<sub>2-4</sub>alkenyl; and halogenated C<sub>1-4</sub>alkyl; each of R<sup>3NA </sup>and R<sup>3NB </sup>is independently selected from: —H; C<sub>1-4</sub>alkyl; C<sub>2-4</sub>alkenyl; and halogenated C<sub>1-4</sub>alkyl; each of R<sup>7NA </sup>and R<sup>7NB </sup>is independently selected from: —H; C<sub>1-4</sub>alkyl; C<sub>2-4</sub>alkenyl; and halogenated C<sub>1-4</sub>alkyl; each of HX<sup>1 </sup>and HX<sup>2 </sup>is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.</p>
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Thiazolidinediones of omega-3 polyunsaturated acids as new insulin sensitizers for treating type2 diabetes (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to thiazolidinedione derivatives of omega-3 fatty acids as insulin sensitizers, and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic diseases, inflammation, renal anemia, and/or Alzheimer's disease: and for modulating activity of peroxisome proliferator-activated receptors (PPARs).</p>
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SEAWEED EXTRACTS, UNSATURATED ALDEHYDES, AND METHODS OF TREATMENT (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The instant invention relates to seaweed extract compositions, processes for isolation, isolated active agents, and methods of treating disease, disorders and conditions in a subject, including, reactive oxygen species (ROS)-mediated diseases and diseases mediated through the activation of the Nrf2-ARE (antioxidant response element) pathway, including proliferative diseases and disorders, Alzheimer's disease, stroke, and certain diseases and disorders of aging and associated with aging and exposure, by use of the extracts, compounds, and compositions thereof.</p>
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BACE1 INHIBITORS (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="59.94mm" file="US20160052920A1-20160225-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED BENZIMIDAZOLES AS NOCICEPTIN RECEPTOR MODULATORS (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The invention provides modulators of the nociceptin receptor (NOP), including both agonists and antagonists. A compound of the invention can be a selective modulator of NOP with respect to the μ- and κ-opioid receptors (MOP and KOP), thus providing a therapeutic method for the treatment of conditions wherein selective NOP modulation is medically indicated and MOP or KOP modulation may be less desirable. A compound of the invention can be a NOP full agonist, partial agonist, inverse agonist, positive or negative allosteric modulator, or a functionally biased agonist. A compound of the invention can be used for the treatment of an anxiety state, post-traumatic stress disorder, addictive disorders (including overuse of alcohol, tobacco, and drugs of abuse such as cocaine, amphetamines, and opitates), misregulated food intake and/or energy expenditure, cough, sleep disorders, grain, pain, depression, or neurodegenerative disorders such as Parkinsons disease or Alzheimers disease.</p>
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PROCESS FOR LARGE SCALE PRODUCTION OF 1-ISOPROPYL-3-{5- [1-(3-METHOXYPROPYL) PIPERIDIN-4-YL]-[1,3,4]OXADIAZOL-2-YL}- 1H-INDAZOLE OXALATE (Fri, 26 Feb 2016)
The present invention relates to a process suitable for adoption to large scale manufacture of l-IsopropyI-3-{5-[l1-(3-methoxypropyl) piperidin-4-yl]-[ 1,3,4] oxadiazol-2-yl}- 1H-indazole oxalate of formula (I), which is a selective 5-HT4 receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.
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APOE4-TARGETED THERAPUTICS THAT INCREASE SIRT1 (Fri, 26 Feb 2016)
A link between ApoE4 allele and sirtuins expression level is identified that is believed to be associated with elevated risk for the promotion of processing of amyloid precursor protein (APP) by the non-amyloidogenic pathway in a mammal leading to elevated risk for Alzheimer's disease. Compounds are identified that upregulate sirtuins (e.g., SirT1) expression levels and appear to be useful in the treatment and/or prophylaxis of MCI and/or Alzheimer's disease.
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INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF (Thu, 25 Feb 2016)
Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
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TREHALOSE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS FOR TREATING NEURODEGENERATIVE DISEASES COMPRISING THE SAME (Thu, 25 Feb 2016)
The invented trehalose derivatives, prepared by introducing multiple units of the guanidine group to the backbone molecules, show excellent blood-brain barrier permeability, and accordingly, it can be easily transported to the brain tissues and utilized for the treatment of neurodegenerative diseases such as Alzheimer's disease and Huntington's disease.
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HETEROCYCLIC ACETIC ACID AMIDE COMPOUND (Thu, 25 Feb 2016)
[Problem] A compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM) is provided. [Means for Solution] The present inventors have studied a compound which has a dopamine D1 receptor positive allosteric modulating activity and is useful as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like, and they have thus found that a heterocyclic acetamide compound has a dopamine D1 receptor positive allosteric modulating activity, thereby completing the present invention. The heterocyclic acetamide compound of the present invention has a dopamine D1 receptor positive allosteric modulating activity and can be used as an agent for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like.
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SYNTHESIS OF AUTOPHAGY INDUCING COMPOUND AND THE USES THEREOF (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to a composition comprising compound of formula CB6 or CB8,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="89.24mm" wi="63.92mm" file="US20160046629A1-20160218-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">the pharmaceutically-acceptable carrier, solvent, the salts thereof or a combination thereof which is used to treat autophagy-associated diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, etc. The present invention also relates to a method of treating these diseases by administering a therapeutically-effective amount of the compound to the subject in need of the treatment. The present invention further relates to the use of this compound in preparation of the composition to treat the diseases.</p>
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Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β, δ-dihydroxy-5-(1-methylethyl)-3-Phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1) (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">Novel forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt designated Form XX, Form XXI, Form XXII, Form XXIII, Form XXIV, Form XXV, Form XXVI, Form XXVII, Form XXVIII, Form XXIX, and Form XXX, characterized by their X-ray powder diffraction, solid-state NMR, and/or Raman spectroscopy are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia (BPH) and Alzheimer's disease.</p>
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Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.80mm" wi="69.85mm" file="US09550762-20170124-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein variables A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, A<sup>8</sup>, and each of R<sup>a</sup>, R<sup>b</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>7 </sup>of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention. </p>
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2,2,2-TRIFLUOROETHYL-THIADIAZINES (Fri, 19 Feb 2016)
The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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BENZYL UREA DERIVATIVES FOR ACTIVATING TGF-BETA SIGNALING (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">Compositions and methods for treatment and prevention of disorders and conditions characterized by reduced TGF-B signaling are described. In particular, the compositions and methods are useful for reducing or eliminating the pathologies associated with Alzheimer's disease. The compositions include urea derivatives containing a piperidine, piperidinium, or a piperidin-4-yl methyl; cycloalkyl, aryl, and fluorobenzyl moieties.</p>
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Therapeutic aryl-amido-aryl compounds and their use (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as “AAA compounds”), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.84mm" wi="51.48mm" file="US09447028-20160920-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Method and compositions for treatment of calcineurin-related diseases (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">Therapeutic compositions for treatment of protein serine/threonine phosphatase-related diseases are obtained by engineering amino acid sequences that disrupt interaction between the protein serine/threonine phosphatase and a protein inhibitor and are provided herein. Calcineurin and PPI are examples of protein serine/threonine phosphatases. RCAN1 is an inhibitor of calcineurin and is overexpressed in patients with serious diseases, such as Down syndrome and Alzheimer's disease. Molecules that bind RCAN1 at regions that interact with calcineurin selectively modulate functions of calcineurin to treat these diseases. Methods of treating a subject for a protein serine/threonine phosphatase-related disease by administering a molecule having an amino acid sequence selected from the group of SEQ ID NOs: 1-19 are further provided.</p>
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C6-azaspiro iminothiadiazine dioxides as bace inhibitors, compositions, and their use (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C2-ring-substituted thiadiazine compounds, including compounds Formula (I): (structure represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>1</sup>, R<sup>4</sup>, ring A, R<sup>A</sup>, m, -L<sub>1</sub>-, R<sup>L</sup>, and ring C 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.54mm" wi="61.04mm" file="US09489013-20161108-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PIPERAZINE DERIVATIVES AS LIVER X RECEPTOR MODULATORS (Fri, 12 Feb 2016)
Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are liver X receptor modulators, and which are useful in the treatment of diseases and disorders associated with the liver X receptor. Also provided are the compounds of Formula (I) and pharmaceutical compositions thereof for treating atherosclerosis, cardiovascular disease, Alzheimer's disease, dermatitis, dyslipidemia, cancer and other diseases or disorders.
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CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 12 Feb 2016)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I): wherein variables A4, A5, A6, A8, and each of Ra, Rb, R1, R2, R3 and R7 of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.
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Glycosidase Inhibitors (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">Compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.00mm" wi="61.47mm" file="US20160031871A1-20160204-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X<sup>1</sup>, X<sup>2</sup>, W, R<sup>1 </sup>to R<sup>5</sup>, L and m have the meaning according to the claims, are glucosidase inhibitors, and can be employed, inter alia, for the treatment of Alzheimer's disease.</p>
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2-Halo-5-Alkynyl-Pyridyl Nicotinic Ligands (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">Disclosed are heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. The compounds are useful for treating a mammal suffering from any one of a range of therapeutic indications, including Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism, trichotillomania, and hypothermia.</p>
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Kappa opioid receptor compounds (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a method of treatment of a disorder or condition that may be treated by administration of the compound, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, Alzheimer's disease, anxiety and addiction, the method comprising administering to a mammal, including a human, in need of such treatment a compound of formula I as described above.</p>
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BENZIMIDAZOLE DERIVATIVES AND USES THEREOF (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and pharmaceutical compositions thereof. The present invention also provides methods and kits using the inventive compounds and pharmaceutical compositions for treating and/or preventing diseases associated with protein aggregation, such as amyloidoses (e.g., Parkinson's disease and Alzheimer's disease), treating and/or preventing neurodegenerative diseases, treating and/or preventing diseases associated with Tar DNA binding protein 43 kDa, reducing or preventing protein aggregation, and/or modulating E3 ubiquitin ligase in a subject in need thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.68mm" wi="75.01mm" file="US20160031824A1-20160204-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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6-AMINO-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL OR 3-AMINOCHROMAN-7-YL DERIVATIVES AS TAAR MODULATORS (Fri, 05 Feb 2016)
The present invention relates to a compound of formula (I), wherein L is –C(O)NH-, -NHC(O)-, -S(O)2NH-, -NH- or -NHC(O)NH-; Ar is phenyl, benzyl, naphthyl or heteroaryl, selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, isoxazolyl or pyrazinyl, wherein Ar may be optionally substituted by one, two or three R1; R1 is hydrogen, lower alkyl, lower alkoxy, halogen, cyano, cycloalkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen, or is phenyl optionally substituted by one or two halogen atoms, CF3O or lower alkyl, or is furanyl, thiazolyl or thiophenyl, optionally substituted by halogen or lower alkyl; X is CH or O; R is hydrogen or halogen; or a pharmaceutically suitable acid addition salt thereof, all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS (Fri, 05 Feb 2016)
The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X1 and X2 are independently, at each occurrence, CR5 or N; Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups; R1 is selected from the group consisting of hydrogen, halogen, C1-C6 alkoxy, -NH2, -NHR6, -NR7R8 and -NH-(R9)n-R10, n being 0 or 1; R2 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, -NH2, -NHR6, - NR7R8 and -NH-(R9)n-R10; R3 is selected from the group consisting of hydrogen, hydroxyl, OR11, -NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, -C(O)NHR11, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups; and R4 is selected from the group consisting of -NH2, -N(R12)(V)pR13, - NH(V)p-OR14, -NHC(O)R15, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
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2-OXA-5-AZABICYCLO[2.2.1]HEPTAN-3-YL DERIVATIVES (Fri, 05 Feb 2016)
The present invention relates to compounds of formula (I), wherein L is a bond, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, CH2C(O)NH-, -CH2NH-, -NH- or -NHC(O)NH-; R1 is hydrogen, lower alkyl, halogen, lower alkoxy-alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen or is phenyl or heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl or pyrazolyl, and wherein phenyl and heteroaryl are optionally substituted by one, two or three substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cycloalkyl or O-CH2-cycloalkyl; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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TASHINONES AND THEIR DERIVATIVES: NOVEL EXCELLENT DRUGS FOR ALZHEIMER DISEASE (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">A method for disaggregating amyloid peptide aggregates the method comprising administering a tanshinone or a tanshinone derivatives to an amyloid peptide aggregate. The method may be useful for disaggregating amyloid peptide aggregates in a patient in need of such treatment, such as patients with Alzheimer's disease.</p>
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P2X7 MODULATORS (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to a compound of Formula (I) or (Ia) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (Ia) and methods comprising administering of compounds of Formula (I) or (Ia) for treating rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomerulonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, <i>chlamydia</i>, neuroblastoma, Tuberculosis, and migraine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.48mm" wi="65.02mm" file="US20160024082A1-20160128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS (Fri, 29 Jan 2016)
The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.
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COMPOUNDS (Fri, 29 Jan 2016)
The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example Alzheimer's disease.
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PYRIDYL-TRIAZABICYCLES (Fri, 29 Jan 2016)
The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS (Thu, 28 Jan 2016)
The present invention provides compositions and methods useful for treating and preventing neurodegenerative disease and neurologically related disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing diseases and disorders with abnormal blood brain barrier (BBB) function, for example neurodegenerative diseases with a permeable BBB, such as but not limited to, Alzheimer's Disease, Huntington's Disease, Parkinson's Disease and Vascular Dementia.
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Phenyl Carbamate Compound and a Composition for Preventing or Treating a Memory Loss-Related Disease Comprising the Same (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention relates to a composition for preventing or treating a memory loss related disease comprising a phenyl carbamate compound and a method for preventing or treating various diseases related to loss of memory therewith. The present invention ensures the enhancement of neuroprotection, such that it is promising for preventing or treating memory loss-related diseases such as dementia and Alzheimer's disease.</p>
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P2X7 MODULATORS (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to a compound of Formula (I) Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) and methods comprising administering to a subject at least one compound selected from compounds of Formula (I) for treating diseases mediated by P2X7 receptor activity, such as rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomerulonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, <i>chlamydia</i>, neuroblastoma, Tuberculosis, and migraine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.40mm" wi="62.40mm" file="US20160016962A1-20160121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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<i>S</i>-imino-<i>S</i>-oxo-iminothiadiazine compounds as BACE inhibitors, compositions, and their use (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides provides certain S-imino-S-oxo iminothiadiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein R<sup>N</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, ring A, R<sup>A</sup>, m, L<sub>1</sub>, and R<sup>L </sup>are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="61.38mm" file="US09428476-20160830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRIDINE DERIVATIVES AS MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.22mm" wi="54.95mm" file="US20160016907A1-20160121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">N-oxides thereof, and pharmaceutically acceptable salts of the compounds or N-oxides; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M1-mediated (or M1-associated) disorders including, e.g., Alzheimer's disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.</p>
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<i>S</i>-imino-<i>S</i>-oxo-iminothiazine compounds as BACE inhibitors, compositions, and their use (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain S-imino-S-oxo iminothiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein R<sup>N</sup>, R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, ring A, R<sup>A</sup>, m, L<sub>1</sub>-, and R<sup>L </sup>are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="61.21mm" file="US09422255-20160823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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C2-azaspiro iminothiazine dioxides as BACE inhibitors, compositions, and their use (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C2-azaspirosubstituted iminothiazine dioxide compounds. 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.</p>
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PYRIDINE DERIVATIVES AS MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 22 Jan 2016)
The present invention provides, in part, compounds of Formula I: (I) N-oxides thereof, and pharmaceutically acceptable salts of the compounds or N-oxides; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds,N-oxides, or salts, and their uses for treating M1-mediated (or M1-associated) disorders including, e.g., Alzheimer's disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.
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Dosing Regimens for Treating And/Or Preventing Cerebral Amyloidoses (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).</p>
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PYRIDAZINE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">This invention relates to pyridazine derivatives, compositions comprising therapeutically effective amounts of those pyridazine derivatives and methods of using those derivatives or compositions in treating central nervous system (CNS) disorders with cognitive impairment that are responsive to agonists of α5 subunit containing GABA<sub>A </sub>receptor, e.g., age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia and cancer-therapy-related cognitive impairment.</p>
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Tau imaging probe (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">An object of the present invention is to provide a probe for imaging a β-sheet structure protein which can be used for the diagnosis of conformational diseases, particularly disease (tauopathy) having a cardinal symptom such as intracerebral accumulation of tau protein, for example, Alzheimer's disease. Another object of the present invention is to provide a compound which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or non-recognized toxicity.</p> <p id="p-0002" num="0000">According to the present invention, the above problems are solved by providing a compound of a formula I (wherein A, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>a </sup>and R<sup>b </sup>are as defined in the present description) or a pharmaceutically acceptable salt or solvate thereof.</p>
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AROMATIC HETEROCYCLIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF (Fri, 15 Jan 2016)
Provided herein are aromatic heterocyclic derivatives or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof used for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and use of such compounds or pharmaceutical compositions thereof for managing or treating 5-HT6 receptor-mediated diseases, especially in the manufacture of a medicament for managing or treating Alzheimer's disease.
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PHARMACEUTICAL COMPOUNDS AND USE OF SAME IN CANCER AND TAUOPATHIES (Fri, 08 Jan 2016)
<p id="p-0001" num="0000">Disclosed are compounds of formula (1)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.</p>
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Monoclonal Antibody (Fri, 08 Jan 2016)
<p id="p-0001" num="0000">The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD).</p>
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SYSTEMS, ASSAYS, AND METHODS FOR DETERMINING RISK FACTORS FOR ALZHEIMER'S DISEASE (Fri, 08 Jan 2016)
A method of determining risk factors for Alzheimer's disease in an individual, including assaying a biological medium obtained from the individual for a biomarker selected from Biomarker 1, Biomarker 2, Biomarker 3, or Biomarker 4, where Biomarker 1 has a mass-to-charge ratio (m/z) of 602.3, Biomarker 2 has a m/z of 804.6, Biomarker 3 has a m/z of 874.6, and Biomarker 4 has a m/z of 804.5, and where the presence of the two or more biomarkers in the individual indicates a risk factor of Alzheimer's disease.
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TETRAHYDROIMIDAZO[1,5-D][1,4]OXAZEPINE DERIVATIVE (Thu, 07 Jan 2016)
A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof works as an mGluR2 antagonist, and is applicable as a therapeutic agent for neurological disorders related to glutamate dysfunction and diseases involving the mGluR2, such as Alzheimer's disease: wherein R is a hydrogen atom, a C 1-6 alkyl group or the like, R 1 is a C 1-6 alkyl group, a C 1-6 alkoxy group or the like, R 2 is a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group or the like, R 3 is a hydrogen atom, a C 1-6 alkyl group or the like, and R 4 is a C 1-6 alkyl group or the like.
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HELICASE-PRIMASE INHIBITORS FOR USE IN A METHOD OF TREATING ALZHEIMER'S DISEASE (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The present invention relates to the use of helicase-primase inhibitors in a method of treating Alzheimer's Disease (AD). Particularly, the present invention relates to the use of helicase-primase inhibitors in a method of treating AD in a subject that is having HSV-1 infection and is having AD or is having HSV-1 infection and is suspected of having AD.</p> <p id="p-0002" num="0000">The provided antiviral helicase-primase inhibitors affect the accumulation of the key AD proteins amyloid beta and abnormally phosphorylated tau that occur during HSV-1 infection.</p>
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FLUORO-[1,3]OXAZINES AS BACE1 INHIBITORS (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="52.83mm" file="US20150376172A1-20151231-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PIPERIDIN-1 -YL AND AZEPIN-1 -YL CARBOXYLATES AS MUSCARINIC M4 RECEPTOR AGONISTS (Fri, 01 Jan 2016)
<p id="p-0001" num="0000">The present invention provides muscarinic M4 receptor agonists of formula (I) and pharmaceutically acceptable salts thereof, wherein m, n, p, q, R, R<sup>2 </sup>and R<sup>3 </sup>are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases such as schizophrenia, Alzheimer's disease and various cognitive disorders as well as in the treatment or alleviation of pain.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.73mm" wi="64.52mm" file="US20150376179A1-20151231-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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N-SUBSTITUTED-5-SUBSTITUTED PHTHALAMIC ACIDS AS SORTILIN INHIBITORS (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">The present invention is directed to N-substituted-5-substituted phthalamic acids which of formula (A). The compounds are considered useful for the treatment of diseases treatment of a neurodegenerative disease, psychiatric disease, motorneuron disease, peripheral neuropathies, pain, neuroinflammation or atherosclerosis such as Alzheimer's disease and Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="54.53mm" file="US20150368231A1-20151224-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Novel 4-(Substituted Amino)-7H-Pyrrolo[2,3-d]Pyrimidines As LRRK2 Inhibitors (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">The present invention provides novel 4,5-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.74mm" wi="54.53mm" file="US20150366874A1-20151224-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.</p>
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METHOD FOR TREATING ALZHEIMER'S DISEASE USING PHARMACOLOGICAL CHAPERONES TO INCREASE THE ACTIVITY OF GANGLIOSIDASES (Thu, 24 Dec 2015)
The present invention relates to a method for treating an individual having Alzheimer's Disease by using pharmacological chaperones to increase the activity of gangliosidase and/or sialidase enzymes involved in ganglioside catabolism.
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2,3-DIHYDROIMIDAZOL[1,2-C]PYRIMIDIN-5(1-H)-ONE BASED IPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA2) INHIBITORS (Fri, 18 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit Lp-PLA<sub>2 </sub>activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA<sub>2</sub>, for example atherosclerosis, Alzheimer's disease.</p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 18 Dec 2015)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu<sub>3</sub>), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.</p>
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Pyrrole Derivatives as Alpha 7 NACHR Modulators (Fri, 18 Dec 2015)
<p id="p-0001" num="0000">Disclosed is a compound of formula (I), wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7 </sup>and m are as described herein, as a modulator of nicotinic acetylcholine receptors particularly α7 subtype, its tautomeric forms, its stereoisomers, its pharmaceutically acceptable salts, its pharmaceutical composition, and its combinations with suitable medicaments. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and therapy of disorders such as Alzheimer's disease, mild cognitive impairment, senile dementia, and the like.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.27mm" wi="60.79mm" file="US20150361041A1-20151217-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRROLO[2,3-C]PYRIDINES AS IMAGING AGENTS FOR NEUROFIBRILARY TANGLES (Fri, 18 Dec 2015)
Pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts are disclosed, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha- synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, the compounds are used as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. Futher, the compounds are useful for measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.
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PYRROLO[2,3-C]PYRIDINES AS IMAGING AGENTS FOR NEUROFIBRILARY TANGLES (Fri, 18 Dec 2015)
The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.
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DUAL INHIBITOR COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISORDERS AND ALZHEIMER'S DISEASE (Fri, 18 Dec 2015)
The present invention relates to Compounds of Formula (I) and pharmaceutical compositions containing the same. It further relates to their use in the prevention or treatment of central nervous system diseases or disorders, in particular, cognitive, neurodegenerative or neuronal diseases or disorders.
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ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF (Fri, 18 Dec 2015)
Disclosed are compounds of Formula (IVA), or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof: Formula (IVA), wherein "RIa", "RIb", "RIc", "RId", "RIe", are defined herein above, which compounds are believed suitable for use in positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) receptors, for example, those found in the cerebral cortex and the hippocampus. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Alzheimer's disease (AD), schizophrenia, and Parkinson's disease (PD), or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
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NOVEL TRICYCLIC 3,4-DIHYDRO-2H-PYRIDO[1,2-A]PYRAZINE-1,6-DIONE DERIVATIVES AS GAMMA SECRETASE MODULATORS (Thu, 17 Dec 2015)
The present invention is concerned with novel tricyclic 3,4-dihydro-2H-pyrido[l,2-a]pyrazine-l,6-dione derivatives of Formula (I) wherein R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, L, Y, Z and X have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament for the treatment of i.a. Alzheimer's disease.
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SUBSTITUTED INDAZOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and dementia</p>
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Oxidisable pyridine derivatives, their preparation and use as anti-alzheimer agents (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">A compound of formula (I) in which the dotted lines indicate the presence of at least one double bond; n=0 to 4; R<sub>3 </sub>and R<sub>4 </sub>are H, or when n=1, R<sub>3 </sub>and R<sub>4 </sub>can also form together a double bond between the carbon atoms, and m=0, 1 or 2, Z is CH or N or Z is C and —CHR<sub>3</sub>— is ═CH— linked by the double bond to cyclopentanone; or −(−)<sub>m</sub>- is absent, and Z is NH, >N-alkyl, >N-phenyl, >N-benzyl or >N heteroaryl; R<sub>8 </sub>is alkyl, aryl or heteroaryl which can be optionally substituted; EWG represents an electron withdrawing group selected from the group comprising COOR, COSR, CONRR′, CN, COR, CF<sub>3</sub>, SOR, SO<sub>2</sub>R, SONRR′, SO<sub>2</sub>NRR′, NO<sub>2</sub>, halogen, heteroaryl; and the pharmaceutical salts and stereisomers thereof. The compounds of formula (I) are potent in the treatment of neurodegenerative diseases such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="73.15mm" file="US09376387-20160628-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Iminothiadiazine dioxides containing a thioamide, amidine, or amide oxime group as BACE inhibitors, compositions, and their use (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C2-ring-substituted iminothiadiazine compounds, or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers. The novel compounds of the invention are 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.50mm" wi="59.69mm" file="US09447085-20160920-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Heterocyclic compound and use thereof (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">Provided is a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.69mm" wi="69.85mm" file="US09499568-20161122-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as defined in the specification, or a salt thereof, which has an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action. The compound of the present invention is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like. </p>
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C2-CARBOCYCLIC IMINOTHIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 11 Dec 2015)
In its many embodiments, the present invention provides certain C2-carbocyclic iminothiazine dioxide compounds, including compounds Formula (I); or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, R2, ring A, RA, m, ring B, RB, n, ring C, RC and p 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.
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Compositions and methods for the treatment of neurological diseases (Wed, 09 Dec 2015)
<p id="p-0001" num="0000">The compositions and compounds of formula I, formula II, formula III and formula IV which includes a salt of valproic acid or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula III and formula IV and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, migraine, schizophrenia, depression, Alzheimer's disease, cancer, HIV and familial adenomatous polyposis.</p>
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C5, C6 oxacyclic-fused thiazine dioxide compounds as BACE inhibitors, compositions, and their use (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C2-ring-substituted iminothiazine compounds, including compounds Formula (I): (structurally represented) or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and, wherein R1, R2, R3, R4, X, ring A, RA, m, -L1-, and RL 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.51mm" wi="59.18mm" file="US09365589-20160614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Omefibrates for Treating Dyslipidemia and Cardiovascular Disease (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to the fibric acid derivatives of omega-3 fatty acids and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic syndrome, cancer, Alzheimer's disease; and their use for modulating activity of peroxisome proliferator-activated receptors (PPARs).</p>
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METHODS OF DETERMINING LEVELS OF FREE AMINO ACIDS AND DIPEPTIDES AND DIAGNOSING ALZHEIMER'S DISEASE (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">Provided herein are methods of diagnosing Alzheimer's disease (“AD”) based on characteristic changes of the levels of certain free amino acids or dipeptides (collectively termed as “AD diagnosis markers”) in the body fluid sample of an individual, carnosine synthesis activities in the plasma, and dopamine synthesis activities in the plasma. Also provided are methods of simultaneously determining the levels of at least two free amino acids or dipeptides in the biological fluid sample of an individual.</p>
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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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5-OXA-2-AZABICYCLO[2.2.2]OCTAN-4-YL AND 5-OXA-2-AZABICYCLO[2.2.1]HEPTAN-4-YL DERIVATIVES AS TAAR1 MODULATORS (Fri, 04 Dec 2015)
The invention relates to compounds of formula (I) wherein.....C.....is -CH2- or -CH2-CH2-; X is -NH-, -C(0)NH- or -NHC(0)NH-; Ar is phenyl or a 5 or 6-membered heteroaryl group containing one or two N atoms; R1 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by cycloalkyl, lower alkoxy substituted by halogen or is cycloalkyl; -( )- is -CH2-; n is 0 or 1; m is 0, 1 or 2; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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METHODS TO TREAT ALZHEIMER'S DISEASE USING APOE INHIBITORS (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">Non-familial late-onset Alzheimer's disease (LOAD), a condition associated with the accumulation of the amyloid precursor protein-derived (APP) Abeta fragment in the brain, can be the consequence of combined genetic and environmental risk factors. One of these risk factors is the presence of the apolipoprotein E4 (APOE4) allele. This invention provides for a neuron model that can be used to screen and identify compounds that can prevent the APOE4-induced pre-LOAD state. This invention provides for methods for the treatment and/or prevention of a neurodegenerative disorder by using an inhibitor of APOE4, such as an antibody inhibitor, or by using an excess of APOE3 protein.</p>
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COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">The present disclosure provides a series of compounds of the formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="12.28mm" wi="50.29mm" file="US20150336975A1-20151126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.</li> </ul> </li> </ul> </p>
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(4E)-4-(4-substituted benzylideneamino)-2,3-dihydro-3-substituted-2-thioxothiazole-5-carbonitriles as A2AR antagonist and process for preparation thereof (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">The present invention provides (4E)-4-(4-substituted benzylideneamino)-2,3-dihydro-3-substituted-2-thioxothiazole-5-carbonitriles of general formula A, below, and a process for the preparation thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.71mm" wi="68.33mm" file="US09518033-20161213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> The compounds of present invention are useful in the treatment of central nervous disorders including, Parkinson disease, Huntington's disease, attention disorder, cognition, Alzheimer disease, depression and hypertension. </p>
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INDOLIN-2-ONE AND 1,3-DIHYDRO-PYRROLO[3,2-c]PYRIDIN-2-ONE DERIVATIVES (Fri, 27 Nov 2015)
The present invention is concerned with indolin-2-one and l,3-dihydro-pyrrolo[3,2-c]pyridin-2-one derivatives of general formula (I) wherein Ar1 is phenyl, pyridinyl or pyrimidinyl; Ar2 is a 5 or 6 membered heteroaryl group, containing 2 or 3 heteroatoms, selected from N, O or S; R1 is hydrogen, lower alkyl, halogen or lower alkoxy; R2 is hydrogen or lower alkyl; R3 is hydrogen, lower alkyl, lower alkyl substituted by hydroxy, cycloalkyl, oxetan-3-yl, pyridinyl, imidazolyl, pyrazolyl, pyrimidinyl, which rings may optionally substituted by lower alkyl, or is -(CH2)3-S(O)2-cyclopropyl; X is CH or N; n is 1 or 2; as well as with a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof, for use in the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.
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