Alzheimer's disease

INHIBITORS OF BETA SECRETASE (Fri, 14 Sep 2018)
The present invention relates to tricyclic inhibitors of beta-secretase having the structure shown in Formula (I) and (II) and the tautomers and the stereoisomeric forms thereof, 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 and other metabolic disorders.
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INHIBITORS OF BETA SECRETASE (Fri, 14 Sep 2018)
The present invention relates to tricyclic inhibitors of beta-secretase having the structure shown in Formula (I) and (II) (I) and (II) and the tautomers and the stereoisomeric forms thereof, 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 and other metabolic disorders.
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INHIBITORS OF BETA SECRETASE (Fri, 14 Sep 2018)
The present invention relates to tricyclic inhibitors of beta-secretase having the structure shown in Formula (I) and (II) (I) and (II) 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 and other metabolic disorders.
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CYCLIC SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE DERIVATIVES (Fri, 14 Sep 2018)
The present invention provides novel cyclic substituted imidazo[4,5- c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof, wherein R1, R2, R4, R5, R6, X and Z 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.
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NOVEL IMIDAZO[4,5-C]QUINOLINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 14 Sep 2018)
The present invention provides novel imidazo[4,5-c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof I wherein R1, R2 and R3 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.
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1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof (Wed, 12 Sep 2018)
<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="96.10mm" wi="69.85mm" file="US10071086-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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N-substituted beta-carbolinium compounds as potent P-glycoprotein inducers (Wed, 12 Sep 2018)
<p id="p-0001" num="0000">The present invention relates to the N-substituted beta-carbolinium compounds of general formula A and formulae I and II wherein, R<sub>1 </sub>and R<sub>2 </sub>groups are selected from halogens or trifluoromethyl; R<sub>3 </sub>group is selected from hydrogen or methyl; Ar is selected from aryl and heteroaryl, X is selected from halogens; and R<sub>1 </sub>and R<sub>2 </sub>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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="100.92mm" wi="74.08mm" file="US10072009-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1-SULFONAMIDO-4-ARYLOXY COMPOUNDS, AND PREPARATION METHOD AND MEDICINAL APPLICATION THEREOF (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Compounds of formula (I) having 1-sulfonamido-4-aryloxy as a basic backbone. A preliminary activity test showed that the compounds provide excellent interference of a binding of Nrf2 by Keap1, thereby activating Nrf2. The compounds have a potential anti-inflammatory activity and can be used to treat a plurality of inflammation-associated diseases, including chronic obstructive pulmonary disease (COPD), Alzheimer's disease, Parkinson's disease, atherosclerosis, chronic kidney disease (CKD), diabetes, gastroenteritis, rheumatoid arthritis, and the like.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="51.65mm" wi="69.85mm" file="US20180251423A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF TAUOPATHIES (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Disclosed herein are compositions and methods for treating tauopathies such as Alzheimer's disease (AD). Also provided herein are methods of reducing or disrupting tau aggregation in a subject, and methods of reducing tau protein in a subject. The methods may include administering to the subject a therapeutic amount of hexachlorophene, or a pharmaceutically acceptable salt thereof. Further provided herein are pharmaceutical compositions comprising hexachlorophene, or a pharmaceutically acceptable salt thereof, for the treatment of a tauopathy in a subject.</p>
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LACTOFERRIN COMPOSITIONS AND METHODS FOR MODULATION OF T CELL SUBTYPES AND TREATMENT OF AUTOIMMUNE DISEASES (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Provided herein are improved compositions comprising lactoferrin and methods for modulating T cell subtypes and their activities in a subject, to improve the balance between anti-inflammatory (Th2) cytokine producing cells and pro-inflammatory (Th1) or Th17 cells, and skew naïve T cells toward a pro-regulatory phenotype, for the treatment and/or amelioration of neurodegen erative or autoimmune diseases and disorders (e.g., inflammatory bowel disease (IBD), amyotrophic lateral sclerosis (ALS), Alzheimers disease, cognitive decline in the elderly resulting from chronic inflammation, and/or rheumatoid arthritis (RA)).</p>
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7,8-DIHYDOXYFLAVONE AND 7,8-SUBSTITUTED FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO (Thu, 06 Sep 2018)
In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.
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SUBSTITUTED DIHYDROBENZOFURAN GLYCOSIDASE INHIBITORS (Fri, 31 Aug 2018)
Compounds of formula (I), wherein R', R'', R, X, 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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SULFOXIMINE GLYCOSIDASE INHIBITORS (Fri, 31 Aug 2018)
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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[1,2,4]-TRIAZOLO [1,5-A]-PYRIMIDINYL DERIVATIVES SUBSTITUTED WITH PIPERIDINE, MORPHOLINE OR PIPERAZINE AS OGA INHIBITORS (Fri, 31 Aug 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. 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 inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.
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HETEROCYCLIC COMPOUND (Thu, 30 Aug 2018)
The present invention provides a compound which has a cholinergic muscarinic M1 receptor positive allosteric modulator activity and may be useful as a medicament such as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, Lewy body dementia and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof. In the formula (I), each symbol is as described in the attached specification.
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Chemical Compounds (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.81mm" wi="58.93mm" file="US20180237441A1-20180823-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>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, X and Y are as defined herein.</p> <p id="p-0004" num="0000">The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.</p>
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RADIOISOTOPE 18F SUBSTITUTED THIAMINE, AND SYNTHESIS METHOD AND USE THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention discloses a radioisotope <sup>18</sup>F substituted thiamine, synthesis method, and use thereof in small animal PET/CT imaging. The radioisotope <sup>18</sup>F substituted thiamine has a structure of</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.99mm" wi="38.44mm" file="US20180237358A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The synthesis method comprises radiochemical synthesis by using existing precursors. In the present invention, the hydroxyl in the hydroxyethyl on the thiazole cycle of thiamine is replaced by radioisotope <sup>18</sup>F, to prepare a PET tracer. The radioisotope <sup>18</sup>F substituted thiamine of the present invention successfully enters the brains of various strains of mice, and the uptake in the brains of thiamine-deficient mice is obviously greater than that in normal control. The present invention is useful in the preparation of a brain imaging tracer for clinical trials of Alzheimer's disease and tumors.</p>
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RADIOLABELED PHARMACEUTICALS AND METHODS OF MAKING AND USING SAME (Fri, 24 Aug 2018)
In one aspect, the invention comprises compounds that bind to the synaptic vesicle protein SV2A and that can be useful as radiotracers for positron emission tomography. In another aspect, the invention comprises methods of imaging the brain, measuring synaptic density or diagnosing neurological diseases such as Alzheimer's disease, psychiatric disorders such as depression, and metabolic disorders such as diabetes comprising detecting the compounds of the invention by positron emission tomography (PET).
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CANNABINOID RECEPTOR MODULATORS (Thu, 23 Aug 2018)
The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB 2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB 1 receptor and the CB 2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.
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COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING NEURODEGENERATIVE DISORDERS (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.</p>
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CHIMERIC COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha 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, organ transplant rejection, and cancer, are provided.</p>
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SINGLE DOMAIN ANTIBODIES CAPABLE OF MODULATING BACE ACTIVITY (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">Described are single domain antibodies with a specificity for BACE1. More specifically, described are single variable-domain antibodies derived from camelids that bind to BACE1 and are capable of inhibiting the activity of BACE1. The antibodies can be used for research and medical applications. Specific applications include the use of BACE1-specific antibodies for the treatment of Alzheimer's disease.</p>
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CO-CRYSTALS OF SUBSTITUTED GLYCINE COMPOUNDS AND USES THEREOF (Fri, 17 Aug 2018)
The present disclosure provides co-crystals of a substituted glycine compound and a co-former compound of Formula (I), compositions comprising such, and uses thereof in treating and/or reducing the risk for a neuropsychiatricdisorder (e.g., schizophrenia, psychotic disorders, depressive disorders, suicidal ideation and/or behavior, obsessive compulsive disorderor Alzheimer's disease). Also provided herein are methods for preparing the co-crystals.
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">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.</p>
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 10 Aug 2018)
<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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VINYL FLUORIDE CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 10 Aug 2018)
<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: wherein variables A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, A<sup>7</sup>, and each of R<sup>a</sup>, R<sup>b</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>8 </sup>R<sup>9 </sup>and R<sup>10 </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 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.80mm" wi="61.81mm" file="US20180222876A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 10 Aug 2018)
<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="57.07mm" file="US20180222862A1-20180809-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">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.</li> </ul> </li> </ul> </p>
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline 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, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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METHODS AND COMPOUNDS FOR DETECTION AND BINDING OF ALEDHYDES (Fri, 10 Aug 2018)
Methods of detecting an aldehyde-containing compound in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde-containing compound. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Biologically relevant aldehydes detected according to the described method can be used to monitor conditions such as brain injury, neurodegenerative disorders such as Alzheimer's disease, diabetes, heart disease, and cancer. Formula (I)
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OGA INHIBITOR COMPOUNDS (Fri, 10 Aug 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors of Formulas (I) and (II). 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 inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.
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5-METHYL-1,2,4-OXADIAZOL-3-YL COMPOUNDS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention provides a compound 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="73.07mm" file="US20180215751A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof, and the use of compounds of Formula I for treatment of neurodegenerative diseases and disorders, such as Alzheimer's disease.</p>
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="52.75mm" file="US20180214455A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRIDAZIN-3(2H)-ONE DERIVATIVES AS MONOAMINE OXIDASE SELECTIVE ISOFORM B INHIBITORS (As Amended) (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">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 medicaments 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="94.57mm" wi="61.47mm" file="US20180215718A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS (Fri, 03 Aug 2018)
Provided 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 associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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COMPOUNDS (Fri, 03 Aug 2018)
Provided 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 associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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COMPOUNDS (Fri, 03 Aug 2018)
Provided 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 associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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COMPOUNDS (Fri, 03 Aug 2018)
The present invention provides 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 associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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ALKOXY BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
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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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
The present invention relates to bis-heteroaryl compounds of formula (I), 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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BICYCLIC BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
The present invention relates to certain bicyclic bis-heteroaryl compounds of Formula (I), 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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N-[4-FLUORO-5-[[(2S,4S)-2-METHYL-4-[(5-METHYL-1,2,4-OXADIAZOL-3-YL)METHOXY]-1-PIPERIDYL]METHYL]THIAZOL-2-YL]ACETAMIDE AS OGA INHIBITOR (Fri, 03 Aug 2018)
The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof, and the use of compounds of Formula (I) for treatment of neurodegenerative diseases and disorders, such as Alzheimer's disease.
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DIHYDROINDENE AND TETRAHYDRONAPHTHALENE COMPOUNDS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The invention provides compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="60.20mm" file="US20180207156A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers, Alzheimer's disease, and conditions associated with demyelination.</li> </ul> </p>
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METHODS OF CHEMICAL SYNTHESIS OF SUBSTITUTED 10H-PHENOTHIAZINE-3,7-DIAMINE COMPOUNDS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention pertains generally to the field of chemical synthesis, and more particularly to methods of chemical synthesis which include the step of preparing a substituted 10H-phenothiazine-3,7-diamine compound of Formula (1) by a step of selective alkylation by reductive amination, in which the corresponding unsubstituted diamine of Formula (4) is reacted with aldehyde/ketone, under reductive amination conditions. The present invention also relates to such methods which incorporate additional subsequent and/or preceding steps, for example, to prepare compounds of Formulae (2) and (3) from compounds of Formula (1), and to prepare compounds of Formula (4) from, for example, compounds of Formulae (5), (6), (7), (8), and (9). Compounds of Formula (1), Formula (2), and Formula (3) are useful, for example, in the treatment of diseases of protein aggregation, such as Alzheimer's disease.</p>
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BIS-FURAN DERIVATIVES AS TRANSTHYRETIN (TTR) STABILIZERS AND AMYLOID INHIBITORS FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY (FAP) (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">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.</p>
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BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.</p>
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HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention provides, in part, heterocyclic spiro compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="58.93mm" file="US20180208608A1-20180726-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, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline 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, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 27 Jul 2018)
<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="32.77mm" wi="65.53mm" file="US20180208607A1-20180726-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, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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ISOCHROMAN COMPOUNDS AND METHODS OF USE THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The invention provides compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="60.37mm" file="US20180207125A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers, Alzheimer's disease, and conditions associated with demyelination.</p>
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 27 Jul 2018)
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, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS (Fri, 27 Jul 2018)
The present invention provides, in part, heterocyclic spiro 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, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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A PHARMACEUTICAL COMPOSITION COMPRISING AN OXAZINE DERIVATIVE AND ITS USE IN THE TREATMENT OR PREVENTION OF ALZHEIMER'S DISEASE (Fri, 27 Jul 2018)
The present invention relates to a pharmaceutical composition comprising an oxazine derivative BACE-1 inhibitor, a process for the preparation thereof, and its use in the treatment or prevention of Alzheimer's disease.
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A FREE BASE OXAZINE DERIVATIVE IN CRYSTALLINE FORM (Fri, 27 Jul 2018)
The invention relates to a solid form, namely crystalline Form A, of Compound 1, (1) and discloses the process for making said solid form of Compound 1. Also disclosed are further solid forms of Compound 1, including its hydrate and amorphous form. The present invention further relates to a pharmaceutical composition comprising crystalline Form A of Compound 1, and methods of using said form and pharmaceutical composition in the treatment or prevention of Alzheimer's disease or cerebral amyloid angiopathy.
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1-(QUINOLIN-4-YL)-3-(6-(TRIFLUOROMETHYL)-PYRIDIN-2-YL)UREA AND 1-(QUINOLIN-4-YL)-3-(6-(TRIFLUOROMETHYL)-PYRAZINE-2-YL)UREA DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 (GSK-3) INHIBITORS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Thu, 26 Jul 2018)
The present invention relates to 1-(quinolin-4-yl)-3-(6-(trifluoromethyl)-pyridin-2-y)urea and 1-(quinolin-4-yl)-3-(6-(trifluoromethyl)-pyrazine-2-yl) urea derivates of formula (I-2): as glycogen synthase kinase 3 (GSK-3) for treating e.g. schizophrenia, Alzheimer's disease, behavioural and psychiatric symptoms of dementia, Parkinson's disease, tauopathies, vascular dementia, acute stroke and other traumatic injuries, cerebrovascular accidents, brain and spinal cord trauma, peripheral neuropathies, bipolar disorders, retinopathies, glaucoma, pain, rheumatoid arthritis and osteoarthritis. A preferred example is e.g. 1-(quinolin-4-yl)-3-(6-(trifluoromethyl)-pyridin-2-yl)urea.
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New compounds (Thu, 26 Jul 2018)
A compound of Formula I or a pharmaceutically acceptable salt, solvate or prodrug thereof; Wherein L1 represents a bond or [CR5R6]-; L2 represents a bond or C(=O)-; L3 represents CH2- or CH2CH2-; X represents O, N(Rx), CH2 or S; A and B each independently represent an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group, each of which is optionally substituted with one or more Q1 or Q2 groups respectively; R1 and R2 independently represent H, halogen, OR7, NR8R9; or optionally substituted as herein defined C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl or C5-12 cycloalkyl; or R1 and R2 together with the carbon atom to which they are attached form C=O, C=C(R10)r11 or an optionally substituted as herein defined cycloalkyl group; wherein Q1, Q2 and R3-11 are as herein defined. L2 is preferably carbonyl. Compositions comprising the disclosed compounds, along with uses of and methods of treatment comprising the compounds and compositions thereof for treating diseases via anatagonism of orexin-1 or orexin-2 receptors are also disclosed. Methods of preparing the disclosed compounds are also provided. The compounds are disclosed to have use in treating substance dependence, addiction; anxiety, panic, compulsive or impulse control disorders; cognitive impairment and Alzheimers disease, particularly binge eating or alcohol, nicotine and/or cocaine addiction.
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METHODS OF TREATING NEURODEGENERATIVE DISEASES USING INDANE ACETIC ACID DERIVATIVES WHICH PENETRATE THE BLOOD BRAIN BARRIER (Fri, 20 Jul 2018)
<p id="p-0001" num="0000">This invention describes the use of indane acetic acid derivatives which are dual PPAR delta/gamma agonists, and which penetrate the Blood Brain Barrier and achieve effective brain to plasma drug levels at non-toxic doses, for the treatment of neurodegenerative diseases including one or more of the following: Alzheimer's Disease (AD); Huntington's Disease (HD); Parkinson's Disease (PD); Amyotrophic Lateral Sclerosis (ALS); Frontal Temporal Dementia (FTD); Corticobasal Degeneration (CBD); Progressive Supranuclear Palsey (PSP); Dementia with Lewy Bodies (DLB); or Multiple Sclerosis (MS).</p>
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Heteroaromatic Compounds and their Use as Dopamine D1 Ligands (Fri, 20 Jul 2018)
<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="34.97mm" wi="62.40mm" file="US20180200253A1-20180719-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds and the uses of such compounds for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension.</p>
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COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASES (Fri, 20 Jul 2018)
<p id="p-0001" num="0000">Compounds, and compositions, methods, and uses thereof, are described herein for treating neurodegenerative diseases and disorders. In particular, vasopressin receptor modulators, and compositions, methods and uses thereof, are described herein for treating neuropsychiatric aspects of neurodegenerative diseases such as Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.</p>
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S1P3 ANTAGONISTS (Fri, 20 Jul 2018)
<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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COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 20 Jul 2018)
<p id="p-0001" num="0000">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), R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6</sup>, 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).</p>
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BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 20 Jul 2018)
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 GABAA receptor agonist (e.g., a α5-containing GABAA 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. It also relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.
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BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 20 Jul 2018)
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 GABAA receptor agonist (e.g., a α5-containing GABAA 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. It also relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.
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HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION (Thu, 19 Jul 2018)
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
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Pyridyl-triazabicycles (Fri, 13 Jul 2018)
<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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DISRUPTION OF THE INTERACTION BETWEEN AMYLOID BETA PEPTIDE AND DIETARY LIPIDS (Fri, 13 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to methods of treating neurodegenerative disorders associated with Alzheimer's disease (AD), Parkinson's disease (PD) and synucleinopathies, such as dementia with Lewy bodies, Down Syndrome (DS) and associated cognitive disorders, multiple system atrophy, and rare neuroaxonal dystrophies, such as Niemann-Pick type C disease (NPC) and Gaucher's disease comprising administering an inhibitor to disrupt the interaction between Aβ or αS and neuronal lipids. The invention further relates to assays for identifying agents that reduce interaction between Aβ or αS and neuronal lipids. Lastly, the invention relates to methods and compositions for intranasal administration of fatty acids or lipids containing fatty acid acyl chains of dietary lipids for promoting central nervous system health and/or prevention or treatment of neurodegenerative disorders.</p>
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BICYCLIC ALKYNE DERIVATIVES AND USES THEREOF (Fri, 13 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prevention and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, autoimmune diseases, metabolic diseases, and neurodegenerative diseases (e.g. autism, autism spectrum disorders, Alzheimer's disease)), as well as methods of treating these diseases</p>
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METHODS AND AGENTS FOR TREATING ALZHEIMER'S DISEASE (Fri, 13 Jul 2018)
<p id="p-0001" num="0000">The present disclosure provides compositions and methods useful for treating or preventing diseases or disorders where beta amyloid accumulation or aggregation contributes to the pathology or symptomology of the disease, for example Alzheimer's disease.</p>
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CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT (Fri, 13 Jul 2018)
<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="66.72mm" wi="75.61mm" file="US20180193491A1-20180712-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 form a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxyl, halogen, un-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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CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT (Fri, 13 Jul 2018)
<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="58.50mm" wi="75.18mm" file="US20180193492A1-20180712-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 form a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxyl, halogen, un-substiuted 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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SMALL MOLECULE INHIBITORS OF NEUTRAL SPHINGOMYELINASE 2 (nSMase2) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 13 Jul 2018)
Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.
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HUMANIZED ANTIBODY AGAINST AMYLOID BETA (Fri, 13 Jul 2018)
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.
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TETRAHYDROOXEPINOPYRIDINE COMPOUND (Thu, 12 Jul 2018)
[Problem] To provide a compound which has a positive allosteric modulating effect (PAM effect) for an ±7 nicotinic acetylcholine receptor (±7 nACh receptor). [Solution] The inventors have achieved the present invention by making studies on PAM effects for an ±7 nACh receptor and confirming that a tetrahydrooxepinopyridine compound has a PAM effect for an ±7 nACh receptor. A tetrahydrooxepinopyridine compound according to the present invention has a PAM effect for an ±7 nACh receptor, and is promising as a prophylactic or therapeutic agent for dementia, cognitive impairment, schizophrenia, Alzheimer's disease, CIAS, negative symptoms of schizophrenia, inflammatory diseases or pain.
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7,8-DIHYDOXYFLAVONE AND 7,8-SUBSTITUTED FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.</p>
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6-AMINO-5-FLUORO-5-(FLUOROMETHYL)-2,3,4,5-TETRAHYDROPYRIDIN-2-YL-PHENYL-5-(METHOXY-D3)-PYRAZINE-2-CARBOXAMIDES AND FLUORINATED DERIVATIVES THEREOF AS BACE1 INHIBITORS (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">The invention provides amidine compounds of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="68.83mm" file="US20180186769A1-20180705-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">for the treatment of neurodegenerative or cognitive diseases, including Alzheimer's Disease.</p>
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BICYCLO[1.1.1]PENTANE INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy-induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).</p>
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SELECTIVE CYSTEINE PROTEASE INHIBITORS AND USES THEREOF (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease).</p>
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IMIDAZODIAZEPINE COMPOUND (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">[Problem]</p> <p id="p-0002" num="0000">Provided is a compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM).</p> <p id="p-0003" num="0000">[Means for Solution]</p> <p id="p-0004" num="0000">The present inventors have studied a compound which has a positive allosteric modulating action (PAM action) on a dopamine D1 receptor and which can be used as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like. Thus, they have found that the imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and thereby completed the present invention. The imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and is expected to be an agent for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like.</p>
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A CASEIN KINASE 1 DELTA INHIBITOR (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">The present invention provides <b>2</b>-Methyl-amino-<b>3</b>-[(<b>4</b>-fluorophenyl)carbonyl]indolizine-<b>1</b>-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof;</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.75mm" wi="69.85mm" file="US20180186786A1-20180705-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.</p>
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 06 Jul 2018)
<p id="p-0001" num="0000">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.</p>
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NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS (Fri, 29 Jun 2018)
<p id="p-0001" num="0000">The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula I. Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine receptor agonists.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.18mm" wi="59.52mm" file="US20180179220A1-20180628-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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6-AMINO-5-FLUORO-5-(FLUOROMETHYL)-2,3,4,5-TETRAHYDROPYRIDIN-2-YL-PHENYL-5-(METHOXY-D3)-PYRAZINE-2-CARBOXAMIDES AND FLUORINATED DERIVATIVES THEREOF AS BACE1 INHIBITORS (Fri, 29 Jun 2018)
The invention provides amidine compounds of Formula (I) for the treatment of neurodegenerative or cognitive diseases, including Alzheimer's Disease.
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THIENOPYRROLE DERIVATIVES FOR USE IN TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 29 Jun 2018)
The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CKla, GSPTl, 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 diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, 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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HYDROXYTRIAZINE COMPOUND AND MEDICAL USE THEREOF (Thu, 28 Jun 2018)
The present invention provides a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and/or cancer including colorectal cancer. The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.
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RADIOISOTOPE FLUORINE-18 SUBSTITUTED THIAMINE, SYNTHESIS METHOD THEREFOR, AND APPLICATIONS THEREOF (Thu, 28 Jun 2018)
The present invention discloses a radioisotope 18 F substituted thiamine, synthesis method, and use thereof in small animal PET/CT imaging. The radioisotope 18 F substituted thiamine has a structure of The synthesis method comprises radiochemical synthesis by using existing precursors. In the present invention, the hydroxyl in the hydroxyethyl on the thiazole cycle of thiamine is replaced by radioisotope 18 F, to prepare a PET tracer. The radioisotope 18 F substituted thiamine of the present invention successfully enters the brains of various strains of mice, and the uptake in the brains of thiamine-deficient mice is obviously greater than that in normal control. The present invention is useful in the preparation of a brain imaging tracer for clinical trials of Alzheimer's disease and tumors.
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Compounds targeting proteins, compositions, methods, and uses thereof (Fri, 22 Jun 2018)
<p id="p-0001" num="0000">The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, 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 diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, 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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CRYSTAL FORMS OF tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride, PROCESSES OF MAKING SUCH FORMS, AND THEIR PHARMACEUTICAL COMPOSITIONS (Fri, 22 Jun 2018)
<p id="p-0001" num="0000">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).</p>
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BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 22 Jun 2018)
<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. It also 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 brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.</p>
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METHOD OF DIAGNOSIS OR TREATMENT OF NEUROLOGICAL DISORDERS WITH P75ECD AND/OR P75 (Fri, 22 Jun 2018)
<p id="p-0001" num="0000">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 non-demented control subject(s).</p>
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CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT (Fri, 22 Jun 2018)
<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="64.52mm" wi="75.69mm" file="US20180169277A1-20180621-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 form a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxyl, halogen, un-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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4H-Pyran Compounds as Insulin-Regulated Aminopeptidase (IRAP) Inhibitors (Fri, 22 Jun 2018)
<p id="p-0001" num="0000">The present disclosure relates generally, but not exclusively, to compounds 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 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.</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, 22 Jun 2018)
<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="33.44mm" wi="60.88mm" file="US20180170920A1-20180621-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:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl optionally substituted by methyl, ethyl, halo or ═O; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl. <br/> 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. </li> </ul> </li> </ul> </p>
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3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOIC ACID USEFUL AS KYNURENINE MONOOXYGENASE INHIBITORS (Fri, 22 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to a compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.29mm" wi="58.59mm" file="US20180170921A1-20180621-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, which are Kynurenine monooxygenase (KMO) inhibitors, which are useful in the treatment of various disorders, which may include, but are not limited to, for diseases such as, 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, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.</p>
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OXAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (insert Formula I structure) wherein variables W, X, Y, R2, R2', R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to beta amyloid (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, and other central nervous system conditions.
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THIAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (see Formula I structure) wherein variables R1, R1', R2, R2', R3, R4, R5, R6, R7, and b of Formula I are defined herein. This disclosure 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, and other central nervous system conditions.
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CYCLOPROPYL FUSED THIAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure 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 A, R1, R2, R2', R3, R4, and R5 of Formula (I) are defined herein. This disclosure 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, and other central nervous system conditions.
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1,4-THIAZINE DIOXIDE AND 1,2,4-THIADIAZINE DIOXIDE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, X, R2, R2', R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure 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, and other central nervous system conditions.
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BICYCLIC OGA INHIBITOR COMPOUNDS (Fri, 22 Jun 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. 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 inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.
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MONOCYCLIC OGA INHIBITOR COMPOUNDS (Fri, 22 Jun 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. 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 inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.
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2,3-DIHYDRO-4H-1,3-BENZOXAZIN-4-ONE DERIVATIVES AS MODULATORS OF CHOLINERGIC MUSCARINIC M1 RECEPTOR (Fri, 15 Jun 2018)
<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: wherein each symbol is as defined in the attached DESCRIPTION.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.62mm" wi="53.09mm" file="US20180162850A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 15 Jun 2018)
<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="24.38mm" wi="69.85mm" file="US20180162853A1-20180614-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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HETEROCYCLIC COMPOUND AND USE THEREOF (Fri, 15 Jun 2018)
<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="22.94mm" wi="69.85mm" file="US20180162875A1-20180614-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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3-(BENZOIMIDAZOL-2-YL)-INDAZOLE INHIBITORS OF THE WNT SIGNALING PATHWAY AND THERAPEUTIC USES THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure 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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BICYCLO[1.1.1]PENTANE INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 15 Jun 2018)
Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy -induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).
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Indazole inhibitors of the WNT signal pathway and therapeutic uses thereof (Fri, 08 Jun 2018)
<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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Amantadine nitrate compounds with neural protective effect, and preparation and medical use thereof (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to amantadine nitrate compounds having neural protective effect, and preparation method and medical use thereof. The compounds have the structure of the general formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.38mm" wi="51.31mm" file="US20180148404A1-20180531-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds have multifunctional mechanisms, including inhibiting NMDA receptors, releasing NO, inhibiting calcium influxes, and having protective effects on cells particularly neurocytes. The compounds can be used in the preparation of medicaments having a cellular protective effect, for prevention or treatment of the diseases related to such as NMDA receptors and elevation of calcium anions in cells, including the diseases related to neurodegeneration such as Alzheimer's disease, Parkinson's disease, cerebral paralysis and glaucoma, and the diseases related to cardio-cerebral-vascular system such as Parkinson's syndrome combined with cerebral arteriosclerosis, as well as respiratory tract infections caused by influenza virus.</p>
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Quinoline Derivatives for Diagnosis and Treatment of Alzheimer's Disease (Fri, 25 May 2018)
<p id="p-0001" num="0000">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.</p>
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Metal Delivery Agents and Therapeutic Uses of the Same (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention relates to metal complexes, processes for their preparation and their use as pharmaceutical or veterinary agents, in particular for the treatment of conditions in which metal delivery can prevent, alleviate or ameliorate the condition. There are a number of clinical conditions which are caused by or associated with abnormal levels of metals (typically low metal levels). Conditions in of this type include cancer and conditions characterised by or associated with oxidative damage, more specifically neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease or Huntington's disease. The invention also relates to ligands useful in the preparation of metal complexes of this type.</p>
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Compositions, Methods and Kits for Detection of Genetic Variants for Alzheimer's Disease (Fri, 25 May 2018)
<p id="p-0001" num="0000">Provided herein are methods, kits, and devices related to genetic variations of neurological disorders. For example, methods, kits, and devices for using such genetic variations to assess susceptibility of developing Alzheimer's disease.</p>
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Therapeutic compounds (Fri, 25 May 2018)
<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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2-SUBSTITUTED AMINO-NAPHTH[1,2-D]IMIDAZOL-5-ONE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS (Fri, 25 May 2018)
Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.
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NOVEL PYRAZOLE DERIVATIVE (Thu, 24 May 2018)
Provided is a novel therapeutic means for Alzheimer's disease. In particular, provided is a compound represented by the following general formula (I): [wherein Ar 1 represents 2-methoxy-4-(2-pyridylmethoxy)phenyl etc. and Ar 2 represents a 1H-indol-6-yl group etc.] or a salt thereof.
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PHENOXYTRIAZOLES (Fri, 18 May 2018)
The present invention relates to a compound of formula I, HetAr is a five or six membered heteroaryl group, selected from wherein R1 is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen, and may be the same or different, if two R1 occur; R2 is lower alkyl or a mono- or polydeutered derivative thereof, lower alkyl substituted by halogen or lower alkoxy, lower alkenyl unsubstituted or substituted by halogen, cycloalkyl or CH2-cycloalkyl unsubstituted or substituted by halogen, heterocycloalkyl or CH2-heterocycloalkyl unsubstituted or substituted by lower alkyl; R3 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or S(0)2-lower alkyl; n is 1, 2 or 3; if n is >1, then R3 may be the same or different; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or an optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 18 May 2018)
Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.
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P2X7 MODULATORS (Thu, 17 May 2018)
The present invention is directed to a compound of Formula (I) or (la). The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (la) and methods comprising administering of compounds of Formula (I) or (la) 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 neuroimmune 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, Glomemlonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, chlamydia, neuroblastoma, Tuberculosis, and migraine.
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BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Thu, 17 May 2018)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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4,4A,5,7-TETRAHYDRO-3H-FURO[3,4-B]PYRIDINYL COMPOUNDS (Sat, 12 May 2018)
The present invention relates to 4,4a,5,7-tetrahydro-3H-furo[3,4-b]pyridinyl compound inhibitors of beta-site APP-cleaving enzyme 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-site APP- cleaving enzyme is involved, such as Alzheimer's disease (AD), mild cognitive impairment, preclinical Alzheimer's disease, 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.
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COMPOSITIONS TARGETING 3-REPEAT TAU FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS, AND METHODS FOR MAKING AND USING THEM (Sat, 12 May 2018)
In alternative embodiments, provided are compositions such as antibodies, e.g., single chain antibodies, that target 3-repeat (3R) Tau for the treatment of neurodegenerative disorders and taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation, and methods for making and using them. In alternative embodiments, provided are brain-penetrating antibodies that specifically recognize 3R Tau, and methods of using them to treat, ameliorate, prevent or decrease the symptoms of neurodegenerative disorders including taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation. Provided are methods for diagnosing a neurodegenerative disorder or a taupathy or any disorder or condition associated with a 3R Tau accumulation.
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SUBSTITUTED 6-MEMBERED ARYL OR HETEROARYL ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Sat, 12 May 2018)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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SUBSTITUTED BICYCLIC HETEROARYL ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Sat, 12 May 2018)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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COMPOUNDS FOR TREATMENT OF NEURODEGENERATIVE DISEASES (Sat, 12 May 2018)
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that can metabolize under physiological conditions to ornithine. The pH and plasma stability of compounds of formula (II) is also described. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
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Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions (Fri, 11 May 2018)
<p id="p-0001" num="0000">The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products.</p>
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Pro-Neurogenic Compounds (Fri, 11 May 2018)
<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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5-SUBSTITUTED INDAZOLE-3-CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure 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, fibrotic disorders, cartilage (chondral) defects, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, and neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.</p>
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COMPOUNDS (Fri, 11 May 2018)
<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="34.29mm" wi="59.86mm" file="US20180127405A1-20180510-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:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl optionally substituted by methyl, ethyl, halo or =0; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl. <br/> 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. </li> </ul> </li> </ul> </p>
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COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 04 May 2018)
<p id="p-0001" num="0000">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).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.25mm" wi="69.85mm" file="US20180118661A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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IMIDAZO ISOINDOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to an imidazo isoindole derivative, a preparation method therefor and a medical use thereof. In particular, the present invention relates to the imidazo isoindole derivative as shown in the formula (I), a preparation method and pharmaceutical composition containing the derivative, and a use thereof for treating diseases with a pathological characteristic of the IDO-mediated tryptophan metabolic pathways. The diseases comprise cancers, Alzheimer's disease, autoimmune diseases, depression, anxiety disorders, cataracts, psychological disorders and AIDS, wherein the substituents in the formula (I) are the same as those defined in the specification.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.61mm" wi="69.85mm" file="US20180118750A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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USE OF SRC PROTEIN INHIBITOR IN THE MANUFACTURE OF A MEDICAMENT FOR THE PROPHYLAXIS AND/OR TREATMENT OF ALZHEIMER'S DISEASE (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention provides use of a Src protein inhibitor N-(2-chloro-6-methylphenyl)-2-{6-[4-(3-hydroxyethyl)-1-piperazinyl]-2 -methyl-4-pyrimidinylamino}-5-thiazolecarboxamide (formula I) in the manufacture of a medicament for the prophylaxis and/or treatment of Alzheimer's disease. An Aβ42 oligomer and a tested drug were applied to primary isolated fetal mouse cerebral cortical neuron for 24 h to test the efficacy of the compound of formula I at different concentrations against Aβ42 oligomer toxicity in vitro, and the results show that the compound of formula I has a wide range of effective concentration and high cell viability at effective concentration.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.28mm" wi="76.12mm" file="US20180117043A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NON-PEPTIDIC GAPDH AGGREGATION INHIBITOR (Fri, 04 May 2018)
<p id="p-0001" num="0000">[Problem] Provided is a non-peptide compound, which can be used as a GAPDH aggregation inhibitor, [Solution] Provided is a GAPDH aggregation inhibitor including as an active ingredient a compound represented by the chemical formula 1 wherein R<sub>1</sub>, R<sub>2</sub>, and R<sub>3 </sub>are each independently a hydrogen atom, a halogen atom, or an aliphatic hydrocarbon group having a carbon number of from 1 to 10, a polysulfurized derivative thereof, or a pharmaceutically acceptable salt thereof. The present compound has a GAPDH aggregation inhibitory activity to suppress intracerebral aggregation of various proteins involved in cerebral neurodegenerative diseases, thereby contributing to improvement in various brain neurological diseases associated with aggregation of these proteins such as Alzheimer's disease, Parkinson's disease, and cerebral infarction, and prevention of advanced seriousness of these diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.09mm" wi="65.02mm" file="US20180116981A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL PIPERAZINE AND PIPERIDINE DERIVATIVES, THEIR SYNTHESIS AND USE THEREOF IN INHIBITING VDAC OLIGOMERIZATION, APOPTOSIS AND MITOCHONDRIA DYSFUNCTION (Fri, 04 May 2018)
<p id="p-0001" num="0000">Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's disease.</p>
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COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF IMIDAZOPYRAZINONES (Fri, 04 May 2018)
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of neurodegenerative disorders such as for example Alzheimer's Disease, Parkinson's Disease or Huntington's Disease. Separate aspects of the invention are directed to the combined use of said compounds for the treatment of neurodegenerative and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of neurodegenerative disorders.
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CRYSTAL OF BIS(8-QUINOLINAMINE) DERIVATIVES (Fri, 04 May 2018)
The present invention provides the crystal of compound N-butyl-2,2'-imino-bis(8-quinolinamine), pharmaceutical composition and use thereof. The crystal compound N-butyl-2,2'-imino-bis(8-quinolinamine) according to the present invention has an excellent property of the preparation of drugs, and can be used for treating abnormal metal ion metabolic-related diseases, as well as the diseases associated with abnormal Tau protein metabolism and abnormal beta-amyloid protein, for example, the neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, ataxia telangiectasia, Creutzfeldt-Jakob disease, Huntington's disease, spinocerebellar ataxia, multiple sclerosis (MS), Parkinson's disease, Alzheimer's disease (AD), primary lateral sclerosis (PLS) and the like.
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COMPOSITIONS, METHODS AND KITS FOR DETECTION OF GENETIC VARIANTS FOR ALZHEIMER'S DISEASE (Fri, 04 May 2018)
Provided herein are methods, kits, and devices related to genetic variations of neurological disorders. For example, methods, kits, and devices for using such genetic variations to assess susceptibility of developing Alzheimer's disease.
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POLYMORPHIC FORMS OF SODIUM BENZOATE AND USES THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present disclosure provides polymorphic forms of sodium benzoate with a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 5.9, 30.2, and 31.2 degrees; or a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 3.7, 5.9, and 26.6 degrees. Also provided herein are methods of preparing the polymorphic forms of sodium benzoate and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, or Alzheimer's disease).</p>
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IMIDAZODIAZEPINE COMPOUND (Thu, 26 Apr 2018)
[Problem] Provided is a compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM). [Means for Solution] The present inventors have studied a compound which has a positive allosteric modulating action (PAM action) on a dopamine D1 receptor and which can be used as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like. Thus, they have found that the imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and thereby completed the present invention. The imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and is expected to be an agent for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like.
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DIKETONES AND HYDROXYKETONES AS CATENIN SIGNALING PATHWAY ACTIVATORS (Thu, 26 Apr 2018)
The present invention discloses ²-diketones, ³-diketones or ³-hydroxyketones or analogs thereof, that activate Wnt/²-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
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COMPOUNDS DERIVED FROM 3-ALKYLAMINE-1H-INDOLYL ACRYLATE AND THEIR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The invention relates to the methods for producing derivatives of 3-alkylamino-1H-indole acrylate (I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of the derivatives according to the invention for the treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulation of the activity of phase II genes activated by the factor Nrf2, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.</p>
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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Provided herein are certain substituted N-aryl and N-heteroaryl piperidine compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R 6 are as defined. The said novel compounds, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor(LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory disease and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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BENZOTHIAZOLE DERIVATIVES AS DYRK1 INHIBITORS (Fri, 20 Apr 2018)
The present invention relates to compounds of Formula (I), which are DYRK1A and/or DYRK1B inhibitors,and their use in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), metabolic disorders such as Metabolic Syndrome or diabetes mellitus, and cancer.
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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1,Q, and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Substituted aryl and heteroaryl ether compounds of the Formula (I) and pharmaceutically acceptable salts thereof, wherein X, R 1, R 2, R 3, L, R 4, L 1, Q, and R 5 are as defined herein. These compounds and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted N-aryl and N-heteroaryl piperidine compounds of the Formula (I): (Formula (I)) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1,Q, R5 and R6 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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Uridine diphosphate derivatives, prodrugs, compositions and uses thereof (Fri, 20 Apr 2018)
This disclosure relates to the use of uridine diphosphate (UDP) derivatives, salts and/or prodrugs thereof for the treatment of inflammatory conditions (e.g., psoriasis) and glaucoma, to prodrugs of UDP derivatives, compositions comprising therapeutically effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs for treating various disorders including, 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, e.g., psoriasis and rheumatoid arthritis.
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BIPHENYL-ETHYL-PYRROLIDINE DERIVATIVES AS HISTAMINE H3 RECEPTOR MODULATORS FOR THE TREATMENT OF COGNITIVE DISORDERS (Thu, 19 Apr 2018)
The present invention relates to biphenyl-ethyl-pyrrolidine derivatives of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that modulate the activity of the histamine H3 receptor (H3R): Compounds of the present invention and pharmaceutical compositions thereof are for use in methods for the treatment of histamine H3-associated disorders, such as treatment of cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as excessive daytime sleepiness, narcolepsy, shift-work sleep disorder, drowsiness as a side effect from a medication, maintenance of vigilance to aid in the completion of tasks and the like, cataplexy, hypersomnia, somnolence syndrome, jet lag, sleep apnea and the like, attention deficit hyperactivity disorder (ADHD), schizophrenia, allergies, allergic responses in the upper airway, allergic rhinitis, nasal congestion, dementia, Alzheimer's disease, pain and pruritus.
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PRODRUG OF 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE (Fri, 13 Apr 2018)
<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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Chimeric compounds targeting proteins, compositions, methods, and uses thereof (Wed, 11 Apr 2018)
<p id="p-0001" num="0000">The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha 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, organ transplant rejection, and cancer, are provided.</p>
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POTENT GAMMA-SECRETASE MODULATORS (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">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 Aβ 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="70.10mm" file="US20180093967A1-20180405-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MATERIALS AND METHODS FOR DIAGNOSIS, PREVENTION AND/OR TREATMENT OF STRESS DISORDERS AND CONDITIONS ASSOCIATED WITH A-BETA PEPTIDE AGGREGATION (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The subject invention concerns materials and methods for treating and/or preventing diseases associated with accumulation of Aβ peptide in neural tissue. The subject invention also concerns materials and methods for treating and/or preventing stress disorders, such as post-traumatic stress disorder (PTSD). In one embodiment, a method of the invention comprises administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, to a person or animal in need of treatment. The methods of the invention can be used to prevent and/or treat Alzheimer's disease, Parkinson's disease, and/or Down's syndrome. The subject invention also concerns compositions that comprise cotinine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or adjuvant.</p> <p id="p-0002" num="0000">The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine. In one embodiment, the method comprises administering cotinine labeled with a detectable label to a person or animal. The presence of labeled cotinine in neural tissue is then determined. The level and/or location of cotinine can be analyzed and a diagnosis made. The subject invention also concerns cotinine labeled with a detectable label. In one embodiment, the cotinine is labeled with a radioisotope that can be detected by Positron Emission Tomography (PET) or single photon emission computed tomography (SPECT).</p>
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HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 06 Apr 2018)
<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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CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 06 Apr 2018)
The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from (II), (III), (IV), and (V), and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive 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.
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CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 30 Mar 2018)
<p id="p-0001" num="0000">The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.72mm" wi="55.88mm" file="US20180085358A1-20180329-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">or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from:</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="59.10mm" wi="53.68mm" file="US20180085358A1-20180329-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">and ring B, n, R<sup>1</sup>, R<sup>2</sup>, R<sup>2A</sup>, R<sup>3</sup>, and R<sup>3A </sup>are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild 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.</p>
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URIDINE MONOPHOSPHATE AND TRIPHOSPHATE DERIVATIVES, COMPOSITIONS AND METHODS OF USE (Fri, 30 Mar 2018)
<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 compounds, 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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Disubstituted piperidines as butyrylcholinesterase inhibitors (Fri, 30 Mar 2018)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="69.17mm" wi="54.53mm" file="US10071964-20180911-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, 30 Mar 2018)
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 compounds, such as agonists, of P2Y6 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.
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HETEROCYCLIC COMPOUND (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present invention provides a compound having an MAGL inhibitory action, which is expected to be useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like.</p> <p id="p-0002" num="0000">The present invention relates a compound represented by the formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="69.85mm" file="US20180079756A1-20180322-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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METHODS AND MATERIALS FOR REDUCING AMYLOID BETA LEVELS WITHIN A MAMMAL (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">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.</p>
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KETONE INHIBITORS OF LYSINE GINGIPAIN (Fri, 23 Mar 2018)
The present invention provides compounds according to Formula (I) as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium Porphyromonas gingivalis. Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease.
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COMPOSITIONS AND METHODS FOR TREATING BETA-AMYLOID RELATED DISEASES (Thu, 22 Mar 2018)
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.
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 16 Mar 2018)
<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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METHODS AND COMPOSITIONS FOR TREATING DEGENERATIVE AND ISCHEMIC DISORDERS (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.</p>
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COMPOSITIONS AND METHODS TO ASSESS THE CAPACITY OF HDL TO SUPPORT REVERSE CHOLESTEROL TRANSPORT (Fri, 16 Mar 2018)
<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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Pyrrolo[2,3-C]pyridines as imaging agents for neurofibrilary tangles (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">The present invention is directed to pyrrolopyridine compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.71mm" wi="58.59mm" file="US10022461-20180717-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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. </p>
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BIOMARKERS FOR THE DIAGNOSIS AND CHARACTERIZATION OF ALZHEIMER'S DISEASE (Fri, 16 Mar 2018)
Embodiments of the present disclosure relate generally to the analysis and identification of global metabolic changes in Alzheimer's disease (AD). More particularly, the present disclosure provides materials and methods relating to the use of metabolornics as a biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. Defining metabolic changes during AD disease trajectory and their relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.
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ALLOSTERIC CORTICOTROPIN-RELEASING FACTOR RECEPTOR 1 (CRFR1) ANTAGONISTS THAT DECREASE P-TAU AND IMPROVE COGNITION (Fri, 16 Mar 2018)
In various embodiments novel allosteric antagonists of the CRFR1 receptor are provided. It discovered that allosteric CRFR1 receptor antagonists are effective to modulate p-Tau levels in Alzheimer's disease (AD) models.
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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, 09 Mar 2018)
<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="20.32mm" wi="69.85mm" file="US20180065943A1-20180308-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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THERAPEUTIC COMPOUNDS (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="53.09mm" file="US20180065936A1-20180308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 09 Mar 2018)
<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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IGF-1R SIGNALING PATHWAY INHIBITORS USEFUL IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 09 Mar 2018)
<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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MACROPHAGES/MICROGLIA IN NEURO-INFLAMMATION ASSOCIATED WITH NEURODEGENERATIVE DISEASES (Fri, 09 Mar 2018)
Described herein are methods of treating neuron inflammation conditions, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of cromolyn or a cromolyn derivative compound.
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INHIBITORS OF DUAL LEUCINE ZIPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 09 Mar 2018)
Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy -induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).
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Synthesis and Utility of New Capgroup Largazole Analogs (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">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.</p>
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INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy-induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).</p>
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6-SUBSTITUTED ESTRADIOL DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 02 Mar 2018)
A method of treating Alzheimer's Disease (AD) with 6-substituted estradiol compounds and their pharmaceutically acceptable salts or prodrugs. The compounds provide for up-regulation of lipoprotein lipase (LPL) and/or apoliprotein C2 (ApoC2), the protein that activates LPL.
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7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto (Fri, 02 Mar 2018)
In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8 substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.
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HETEROCYCLIC COMPOUND (Thu, 01 Mar 2018)
The present invention provide a compound having an orexin receptor antagonistic activity, which is expected to be useful as medicaments such as agents for the prophylaxis or treatment of sleep disorder, depression, anxiety disorder, panic disorder, schizophrenia, drug dependence, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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IMIDAZO ISOINDOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF (Thu, 01 Mar 2018)
The present invention relates to an imidazo isoindole derivative, a preparation method therefor and a medical use thereof. In particular, the present invention relates to the imidazo isoindole derivative as shown in the formula (I), a preparation method and pharmaceutical composition containing the derivative, and a use thereof for treating diseases with the pathological characteristic of IDO-mediated tryptophan metabolic pathways. The diseases comprise cancers, Alzheimer's disease, autoimmune diseases, depression, anxiety disorders, cataracts, psychological disorders and AIDS, wherein the substituents in the formula (I) are the same as those defined in the description.
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HETEROCYCLIC COMPOUND (Fri, 23 Feb 2018)
<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="36.75mm" wi="53.09mm" file="US20180050996A1-20180222-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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ANTIBODY HIGHLY SPECIFICALLY RECOGNIZING TURN STRUCTURE AT 22- AND 23-POSITIONS IN AMYLOID BETA (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">Provided is an antibody or an immunologically reactive fragment thereof which targets exclusively an Aβ having a specific turn structure of Aβ (a toxic conformer of Aβ). Also provided are a medicinal composition comprising, as an active ingredient, an antibody that specifically recognizes a toxic conformer of Aβ, a kit for assaying a toxic conformer of Aβ, a diagnostic agent for Alzheimer's disease, etc.</p>
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 23 Feb 2018)
The present invention relates to compounds of Formula A and pharmaceutical compositions thereof that modulate the activity of the 5-HT2C receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of a 5-HT2C receptor-mediated disorder, such as, 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 and the like, obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders, 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 are compositions comprising a compound herein, optionally in combination with a supplemental agent.
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INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF (Thu, 22 Feb 2018)
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.
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Method of Treating Neurological Conditions with Extract of Nerium Species or Thevetia Species (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">A method of treating neurological condition in a subject by administration of a neuroprotective composition of a mixture of two or more triterpenes. Alzheimer's disease, Huntington's disease, stroke or Parkinson's disease are treated by administering a therapeutically effective amount of the neuroprotective composition to a subject.</p>
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COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">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.</p>
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METHOD OF DIAGNOSIS, PROGNOSIS OR TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">Methods for the diagnosis and prognosis of neurodegenerative diseases, such as a Tauopathy or Alzheimer's disease, are described. Compositions and methods for the treatment of neurodegenerative diseases are also described.</p>
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METHODS FOR TREATING PROTEINOPATHIES (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">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.</p>
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Oxazine Derivative for Use in the Prevention of Alzheimer's Disease in at Risk Patients (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to an oxazine derivative BACE-1 inhibitor and pharmaceutical compositions comprising such oxazine derivative for use in the prevention of Alzheimer's disease in a patient at risk of developing clinical symptoms of Alzheimer's disease, and in particular, wherein the patient at risk of developing clinical symptoms of Alzheimer's disease carries one or two copies of the ApoE4 allele.</p>
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INHIBITORS OF JUN N-TERMINAL KINASE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.36mm" wi="18.88mm" file="US20180037577A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt or solvate thereof, wherein ring A, C<sup>a</sup>, C<sup>b</sup>, Z, R<sup>5</sup>, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.</p>
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GP130 MODULATORS (Fri, 09 Feb 2018)
There are provided, inter alia, compounds and methods useful for the treatment of neurological conditions, such as neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
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HETEROCYCLIC COMPOUND (Thu, 08 Feb 2018)
The present invention provides a compound having an MAGL inhibitory action, which is expected to be useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates a compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof.
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Allosteric modulators of nicotinic acetylcholine receptors (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.65mm" wi="69.85mm" file="US09926285-20180327-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Method of immunization for reducing toxic damaged caused by oligomeric form of the amyloid-beta protein with stable amyloid beta monomers and oligomers (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.</p>
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THIOFLAVIN DERIVATIVES FOR USE IN ANTEMORTEM DIAGNOSIS OF ALZHEIMER'S DISEASE AND IN VIVO IMAGING AND PREVENTION OF AMYLOID DEPOSITION (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">This invention relates to novel thioflavin derivatives, methods of using the derivatives in, for example, in vivo imaging of patients having neuritic plaques, pharmaceutical compositions comprising the thioflavin derivatives and method of synthesizing the compounds. The compounds find particular use in the diagnosis and treatment of patients having diseases where accumulation of neuritic plaques are prevalent. The disease states or maladies include but are not limited to Alzheimer's disease, familial Alzheimer's disease, Down's Syndrome and homozygotes for the apolipoprotein E4 allele.</p>
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GLYCINE METABOLISM MODULATORS AND USES THEREOF (Fri, 02 Feb 2018)
The present invention relates to a compound of general formula (I) and/or its solvates, hydrates and pharmaceutically acceptable salts, which are modulators of glycine metabolism. The present invention also relates to the methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of disorders/conditions/diseases involving, relating to or associated with glycine metabolism or a pathway where glycine decarboxylase (GLDC, or glycine cleavage system) plays a role. In a preferred embodiment the disorders/conditions/disease is cancer, inflammatory conditions, Alzheimer's disease, metabolic disorders and CNS disorders.
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Compounds (Fri, 02 Feb 2018)
COMPOUNDS 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).
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Compounds (Fri, 02 Feb 2018)
COMPOUNDS 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).
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Co-crystals of substituted glycine and uses thereof (Wed, 31 Jan 2018)
<p id="p-0001" num="0000">The present disclosure provides co-crystals of a substituted glycine compound and a co-former compound of Formula (I):</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="US09877942-20180130-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> compositions comprising such, and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, suicidal ideation and/or behavior, obsessive compulsive disorder or Alzheimer's disease). Also provided herein are methods for preparing the co-crystals. </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 (Wed, 31 Jan 2018)
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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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">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.</p>
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COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES (Fri, 26 Jan 2018)
The present invention relates to novel compounds of the 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.
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ISOQUINOLINE DERIVATIVES AS PERK INHIBITORS (Fri, 26 Jan 2018)
The invention is directed to substituted isoquinoline derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states: (I) wherein R1, R2, R3, R4, R5, R6, R7 and X are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, ather osclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES (Fri, 26 Jan 2018)
The present invention relates to novel compounds of the formula (II) 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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AN OXAZINE DERIVATIVE FOR USE IN THE PREVENTION OF ALZHEIMER'S DISEASE IN AT RISK PATIENTS (Fri, 26 Jan 2018)
The present invention relates to an oxazine derivative BACE-1 inhibitor and pharmaceutical compositions comprising such oxazine derivative for use in the prevention of Alzheimer's disease in a patient at risk of developing clinical symptoms of Alzheimer's disease, and in particular, wherein the patient at risk of developing clinical symptoms of Alzheimer's disease carries one or two copies of the ApoE4 allele.
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New substituted cyclohexanone compound, and preparation method and application thereof (Sat, 20 Jan 2018)
The invention relates to a substituted cyclohexanone compound with the structure as shown in a formula (I), and a preparation method thereof. The preparation method comprises the following steps: a, performing reaction on a compound 1 and a hydroxyl protective agent under the existence of acid to obtain a compound 2 with 4,5-position hydroxyl protected by acetonylidene; b, performing reaction on the compound 2 and sulfonyl chloride under the existence of alkali to obtain a compound 3; c, performing reaction on the compound 3 and ammonium carbonate to obtain a compound 4; and d, performing acetonylidene deprotection on the compound 4 under the existence of acid to obtain the substituted cyclohexanone compound. The substituted cyclohexanone compound has remarkable activity on acetylcholin esterase, the activity is obviously more excellent than that of a positive medicine huperzine A, and the substituted cyclohexanone compound can be used for preparing medicines for treating Alzheimer's disease. The structural formulas of the compound of the formula (I), the compound 1, the compound 2, the compound 3 and the compound 4 are as shown in the description.
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Antibodies Specific for Hyperphosphorylated Tau and Methods of Use Thereof (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to a class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396) with improved affinity, as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and other tauopathies.</p>
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FUSED PYRIMIDINE DERIVATIVES (Fri, 19 Jan 2018)
The present invention relates to a compound of formula (I) wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, -CH2-C3-6-cycloalkyl or bridged C4-6-cycloalkyl, substituted by one, two or three halogen atoms, or by lower alkyl or lower alkyl substituted by halogen;R2 is a five or six membered heteroaryl group, selected from or wherein R6 is hydrogen, lower alkyl, halogen or lower alkoxy; and R7 is hydrogen, lower alkoxy or halogen; R3 is lower alkyl or lower alkyl substituted by hydroxy: R4 is hydrogen or lower alkyl; R5 is hydrogen or lower alkyl; n is 1 or 2; -( )n- is -CH2- or -CH2CH2- for n being 1 or 2; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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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, 12 Jan 2018)
<p id="p-0001" num="0000">Novel forms of [R-(R*,R*)]-<b>2</b>-(<b>4</b>-fluorophenyl)-β,δ-dihydroxy-<b>5</b>-(<b>1</b>-methylethyl)-<b>3</b>-phenyl-<b>4</b>-[(phenylamino)carbonyl]-<b>1</b>H-pyrrole-<b>1</b>-heptatonic 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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FUSED PYRIMIDINE DERIVATIVES (Fri, 12 Jan 2018)
The present invention relates to compounds of formula (I), wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, -CH2-C3-6-cycloalkyl, or bridged C3-5-cycloalkyl, optionally substituted by one, two or three substituents, selected from halogen, lower alkyl or lower alkyl substituted by halogen; R2 is hydrogen, halogen, lower alkoxy, lower alkyl substituted by halogen or lower alkoxy substituted by halogen; R3 is a five membered heteroaryl group, selected from (A), (B), (C), (D); wherein R6 is hydrogen or lower alkyl; R7 is halogen or lower alkyl; R8 is hydrogen or lower alkyl; R9 is hydrogen or lower alkyl; R4 is lower alkyl or lower alkyl substituted by hydroxy; R5/R5' is independently from each other hydrogen or lower alkyl; -( )n- is –CH2- or –CH2CH2- for n being 1 or 2; X is CH or N; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Fri, 05 Jan 2018)
<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="39.29mm" wi="69.85mm" file="US20180000780A1-20180104-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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COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 05 Jan 2018)
<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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5,7-Dihydro-Pyrrolo-Pyridine Derivatives (Fri, 05 Jan 2018)
<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="24.47mm" wi="76.20mm" file="US20180002331A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R<sup>1</sup>, R<sup>2</sup>, L, A, and E are as described herein; 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 M4-mediated (or M4-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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5,7-DIHYDRO-PYRROLO-PYRIDINE DERIVATIVES FOR TREATING NEUROLOGICAL AND NEURODEGENERATIVE DISEASES (Fri, 05 Jan 2018)
The present invention provides, in part, compounds of Formula (I): or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N- oxide, wherein: R1, R2, L, A, and E are as described herein; 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 M4-mediated (or M4- 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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BICYCLO[3.2.1]OCTYL AMIDE DERIVATIVES AS ALLOSTERIC MODULATORS OF THE METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLU5 OR MGLUR5) FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM (CNS) DISORDERS (Thu, 04 Jan 2018)
The present invention provides bicyclo[3.2.1]octyl amide derivatives of formula (I): wherein L, R 1 and R 2 are as defined herein, as allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 or mGluR5) for the treatment of central nervous system (CNS) disorders, such as e.g. mood disorders, anxiety, schizophrenia, Alzheimer's disease, Parkinson's disease and multiple sclerosis.
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PDE10 inhibitors and related compositions and methods (Wed, 03 Jan 2018)
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 thereoffor inhibiting PDE10 in a warm-blooded animal in need of the same.
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3.ALPHA.-ETHYNYL, 3.BETA.-HYDROXY-5.ALPHA.-PREGNAN-20-OXIME FOR USE IN THE TREATMENT OF CNS DISORDERS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">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 (GABA<sub>A</sub>-R) complex and in the treatment of disorders such as hepatic encephalopathy, Down's syndrome and Alzheimer's disease.</p>
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MAP KINASE MODULATORS AND USES THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention provides for novel MAP kinase inhibitors and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38α MAP kinase inhibitors. The invention further provides for methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease.</p>
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Iminothiadiazine dioxides bearing an amine-linked substituent as BACE inhibitors, compositions, and their use (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">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 R<sup>1</sup>, R<sup>2</sup>, ring A, R<sup>A</sup>, m, ring B, R<sup>B</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.23mm" wi="59.10mm" file="US10071998-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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N-(SUBSTITUTED-PHENYL)-SULFONAMIDE DERIVATIVES AS KINASE INHIBITORS (Fri, 29 Dec 2017)
The invention relates to N-(substituted-phenyl)-sulfonamide compounds, which are extremely useful as inhibitors of protein kinases (e.g. PERK kinase) and accordingly can be used for the treatment of cell proliferative disorders, such as cancer, or diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
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NEW THIOSEMICARBAZONE COMPOUNDS AND ANALOGUES THEREOF (Fri, 29 Dec 2017)
The present invention relates to new multi-functional compounds that are useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing neurodegenerative diseases.
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C5-C6-oxacyclic fused iminopyrimidinone compounds as bace inhibitors, compositions, and their use (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">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 R<sup>N</sup>, R<sup>1</sup>, R<sup>A</sup>, ring A, m, n, -L<sub>1</sub>-, ring B, R<sup>B</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.36mm" wi="70.27mm" file="US10047098-20180814-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </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, 22 Dec 2017)
<p id="p-0001" num="0000">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)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="44.45mm" file="US20170362198A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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.</p>
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CO-CRYSTALS OF SODIUM BENZOATE AND USES THEREOF (Fri, 22 Dec 2017)
Provided are co-crystals of a sodium benzoate compound and a co-former compound of Formula (I). Also provided herein are methods of preparing the co-crystals and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, or Alzheimer's disease) or a glucose or lipid metabolic disorder (e.g., obesity, diabetes, hypercholesterolemia, hypertension, or hyperlipidemia).
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ADAMANTANE COMPOUNDS (Fri, 22 Dec 2017)
The present invention relates to new multi-functional compounds that are useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing neurodegenerative diseases.
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Curcumin derivatives, and preparing method and applications thereof (Sat, 16 Dec 2017)
The invention belongs to the technical field of biological medicine, and particularly relates to curcumin derivatives, and a preparing method and applications thereof. The curcumin derivatives are compounds of a formula I or pharmaceutically acceptable salts thereof, and solvates, enantiomers, diastereoisomers and tautomers of the compounds of the formula I or pharmaceutically acceptable salts thereof or mixtures thereof in any ratio, including racemic mixtures. The derivatives have novel structures, good water solubility, high sensitivity, good selectivity, good optical stability, high bioavailability and good affinity with A[beta]1-42 aggregates, and can inhibit auto-polymerization of beta-amyloid protein. Accordingly, the derivatives provided can be adopted as fluorescent molecular probes for A[beta] protein plaque imaging, and can also be used for treating Alzheimer's disease.
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Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators (Sat, 16 Dec 2017)
Novel methods for reduction or elimination the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly compounds having the general structure. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.
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DISRUPTION OF THE INTERACTION BETWEEN AMYLOID BETA PEPTIDE AND DIETARY LIPIDS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to methods of treating neurodegenerative disorders associated with Alzheimer's disease (AD), Parkinson's disease (PD) and synucleinopathies, such as dementia with Lewy bodies, Down Syndrome (DS) and associated cognitive disorders, multiple system atrophy, and rare neuroaxonal dystrophies, such as Niemann-Pick type C disease (NPC) and Gaucher's disease comprising administering an inhibitor to disrupt the interaction between Aβ or αS and neuronal lipids. The invention further relates to assays for identifying agents that reduce interaction between Aβ or αS and neuronal lipids. Lastly, the invention relates to methods and compositions for intranasal administration of fatty acids or lipids containing fatty acid acyl chains of dietary lipids for promoting central nervous system health and/or prevention or treatment of neurodegenerative disorders.</p>
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DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">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-<sub>κ</sub>B 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.69mm" wi="57.40mm" file="US20170354639A1-20171214-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SULFUR-CONTAINING COMPOUNDS TARGETING VESICULAR ACETYLCHOLINE TRANSPORTER (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The present invention generally relates to various compounds that are useful as vesicular acetylcholine transporter (VAChT) ligands. The invention further relates to methods of using these compounds and their radiolabeled analogs for the detection of neurodegenerative diseases including Parkinson's disease (PD), and Alzheimer's disease (AD).</p>
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STABLE AMYLOID BETA MONOMERS AND OLIGOMERS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.</p>
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CHEMCICAL COMPOUNDS (Fri, 15 Dec 2017)
The invention is directed to substituted pyrrolidine derivatives. Specifically, the invention is directed to compounds according to Formula III: wherein A, B, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, R10, R30, Y1, Y2, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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CHEMICAL COMPOUNDS AS ATF4 PATHWAY INHIBITORS (Fri, 15 Dec 2017)
The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: wherein A, B, X, Y, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Pro-Neurogenic Compounds (Fri, 15 Dec 2017)
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.
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NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-D]PYRIMIDINES AS LRRK2 INHIBITORS (Thu, 14 Dec 2017)
The present invention provides novel 4,5-disubstituted-7 H -pyrrolo[2,3- d ]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof wherein R 1 , R 2 , R 3 , R 4 and R 5 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.
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3-(6-alkoxy-5-chlorobenzo[d]isoxazol-3-yl)propanoic acid useful as kynurenine monooxygenase inhibitors (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.37mm" wi="58.42mm" file="US09932328-20180403-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:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or ═O; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl; <br/> 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, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure. </li> </ul> </li> </ul> </p>
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Inhibitors of lysine gingipain (Fri, 08 Dec 2017)
<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="US09988375-20180605-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPETITIVE INHIBITORS OF INVARIANT CHAIN EXPRESSION AND/OR ECTOPIC CLIP BINDING (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The invention relates to methods for modulating the immune function through targeting of CLIP molecules. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including autoimmune disease, cancer, Alzheimer's disease, allergic disease, transplant and cell graft rejection, HIV infection and other viral, bacterial, and parasitic infection, and AIDS. Methods are also provided for preparing a peptide having the property of being able to displace CLIP by feeding one or more peptide sequences into software that predicts MHC Class II binding regions in an antigen sequence and related products.</p>
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HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to novel 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, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., 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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Process for preparing N-(5-(3-(7-(3-fluorophenyl)-3H-imidazo [4,5-C]pyridin-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Provided herein is a synthetic process for preparing a compound of Formula (1).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.78mm" wi="68.58mm" file="US10072004-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The disclosure also provides useful intermediates and salts, amorphous and polymorph forms of the compound of Formula (1). These compounds are useful for various disease including cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, and osteoarthritis as well as Wnt-related diseases.</p>
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COMPOUNDS (Fri, 08 Dec 2017)
The present technology relates to compounds, kits, compositions, and methods useful for the treatment of numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, defective wound healing, and/or sensorineural hearing and vision loss.
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2-amino-3-substituted mercaptopropionate derivative, preparation method and application thereof (Wed, 06 Dec 2017)
The invention relates to a 2-amino-3-substituted mercaptopropionate derivative, a preparation method and application thereof. The 2-amino-3-substituted mercaptopropionate derivative has a structure as shown in the formula (A). The invention also relates application of the 2-amino-3-substituted mercaptopropionate derivative used as a medicine for treating and/or preventing neurodegenerative disease, especially Alzheimer's disease.
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2-amino-5,5-difluoro-6-(fluoromethyl)-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 inhibitors (Fri, 01 Dec 2017)
<p id="p-0001" num="0000">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 Aβ deposits is beneficial such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="58.67mm" file="US10058540-20180828-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Thiazole triazole-6-acetamide derivative and application (Sat, 25 Nov 2017)
The invention discloses a thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative as shown in formula I or a pharmaceutically acceptable hydrate and salt thereof. The derivative comprises a stereisomer or tautomer thereof; R1 in the formula I is hydrogen, methyl, halogen, hydroxy, methoxy group, acetyl, propionyl, nitro or alkoxy; R2 and R3 are independently selected from C1-C6 alkyl or R2 and R3 and nitrogen atoms connected with the R2 and R3 are formed into pyrryl, piperidyl, morpholinyl, N-methyl piperazine and N-phenylpiperazine. The thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative disclosed by the invention has an obvious restraining function to acetylcholin esterase and is used for enhancing the memory of the patients suffering from dementia and Alzheimer's disease. The invention also relates to a preparation method of the compound and application of the compound for preparing the drug for treating the senile dementia.
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METHOD FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES (Fri, 24 Nov 2017)
Disclosed is an in vitro method for the determination of neurodegenerative diseases, in particular Parkinson's disease and Alzheimer's disease, based on measuring, in a peripheral blood sample, the heteromeric complexes of a-synuclein with β-amyloid 1-42 and a-syn with tau protein. Further subjects of the invention are an immunochemical assay for the quantitation of said heteromeric complexes and a diagnostic kit for conducting the assay.
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OXOINDOLINE DERIVATIVES AS PROTEIN FUNCTION MODULATORS (Fri, 24 Nov 2017)
The present invention provides chimeric compounds of formula (II) that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CKl-alpha 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, organ transplant rejection, and cancer, are provided.
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4H-pyran compounds as insulin-regulated aminopeptidase (IRAP) inhibitors (Fri, 24 Nov 2017)
The present disclosure relates to <i>4H</i>-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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CAMSYLATE SALT (Fri, 24 Nov 2017)
A camsylate salt of (1r,1'R,4R)- 4-methoxy-5 "-methyl-6'-[5 -(prop-i -yn- 1 -yl)pyridin-3 -yl] 3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine, pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating AB-related pathologies such as Alzheimer's Disease, Down's syndrome, B-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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COMPOUNDS TO PROMOTE NORMAL PROCESSING OF APP (Fri, 17 Nov 2017)
In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of compound C41 to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly enhances sAPPα, lowers Aβ, p-Tau, inhibits the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) and improves memory in a mammal are provided.
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INHIBITION OF BETA-2 NICOTINIC ACETYLCHOLINE RECEPTORS TO TREAT ALZHEIMER'S DISEASE PATHOLOGY (Fri, 17 Nov 2017)
The invention provides methods of reducing development of mild cognitive impairment and/or learning disorders and/or memory disorders in a subject suspected to have or suffering from Alzheimer's disease (AD). In some embodiments,the methods comprise administering a therapeutically effective amount of a beta-2 nicotinic acetylcholine receptor (n AChR) antagonist and/or beta-2 nAChRnegative allosteric modulator (NAM) to the subject over a therapeutic dosing period to thereby reduce the rate of development of mild cognitive impairment and/or learning disorders and/or memory disorders in the subject over the therapeutic dosing period.
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Heterocyclic derivatives and their use in the treatment of neurological disorders (Fri, 10 Nov 2017)
<p id="p-0001" num="0000">The invention relates to novel heterocyclic compounds of the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.98mm" wi="64.52mm" file="US10035794-20180731-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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 or diabetes via inhibition of BACE-1 or BACE-2. </p>
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Compounds and their use as BACE inhibitors (Fri, 10 Nov 2017)
<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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2-amino-6-(difluoromethyl)-5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 inhibitors (Fri, 10 Nov 2017)
<p id="p-0001" num="0000">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 Aβ deposits is beneficial such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="69.85mm" file="US10045974-20180814-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ISOTOPICALLY MODIFIED COMPOSITION AND THERAPEUTIC USES THEREOF (Fri, 10 Nov 2017)
This disclosure relates to isotopically modified amino acids and their pharmaceutical or nutritional uses in stabilizing pharmaceutical protein-based formulations, proteins with long life span, and preventing or treating disease such as Alzheimer's disease. Specifically, the disclosure provides protein drugs having increased stability comprising an L-aspartate (L-Asp) residue or an L-asparagine (L-Asn) residue, wherein the L-Asp residue or the L-Asn residue comprises a deuterium atom.
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TRIFLUOROACETHYDRAZIDE COMPOUND AS WELL AS PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN PREPARING MEDICAMENT (Thu, 09 Nov 2017)
The present invention relates to trifluoroacetyl hydrazide compounds and methods of preparation and uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells.. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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Compounds and their use as BACE inhibitors (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">The present application relates to compounds of formula (I), (Ia), or (Ib) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing 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.</p>
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline 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, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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AMYLOID BINDING AGENTS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">There are provided compounds and methods for the detection of amyloids and treatment of diseases related to amyloids including Alzheimer's disease and other related amyloid-based neurodegenerative diseases.</p>
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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, 03 Nov 2017)
<p id="p-0001" num="0000">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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.75mm" wi="69.85mm" file="US10059669-20180828-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MOFEZOLAC DERIVATIVES AS MULTI-FUNCTIONS SELECTIVE COX-1 INHIBITORS (Fri, 03 Nov 2017)
The invention relates to a new class of compounds of formula (I) targeting COX-1. The invention also relates to the use of some of such compounds as a tool to investigate the structure and function of the enzyme, in the treatment targeting COX-1 or detection of COX-1 in relating disorders or diseases such as cancer and neuroinflammation, in particular in neurological (e.g. autism spectrum disorders) and neurodegenerative diseases (e.g. Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury (TBI), HIV dementia and prion diseases), and in gynecological tumour (e.g. ovarian cancer), neck and head tumor, and haematological tumours (e.g. multiple myeloma) and in the detection of COX-1 in "in vitro" (cells and tissues) and in "in vivo".
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline 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, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.
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ANTIBODY HIGHLY SPECIFICALLY RECOGNIZING TURN STRUCTURE AT 22- AND 23-POSITIONS IN AMYLOID BETA (Thu, 02 Nov 2017)
Provided is an antibody or an immunologically reactive fragment thereof which targets exclusively an A² having a specific turn structure of A² (a toxic conformer of A²). Also provided are a medicinal composition comprising, as an active ingredient, an antibody that specifically recognizes a toxic conformer of A², a kit for assaying a toxic conformer of A², a diagnostic agent for Alzheimer's disease, etc.
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Application of 10B-containing compound in preparation of medicine specifically combined with beta amyloid protein (Wed, 01 Nov 2017)
The invention provides application of a 10B-containing compound in preparation of a medicine specifically combined with a beta amyloid protein, wherein the medicine specifically combined with the beta amyloid protein can reduce or eliminate the beta amyloid protein in an irradiation process of a neutron beam transmitted by a neutron capture treatment device after the beta amyloid protein is combined, so that Alzheimer's disease is further treated. The invention provides a new method for treatment of the Alzheimer's disease.
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7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.</p>
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Pro-Neurogenic Compounds (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">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 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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Tetrahydronaphthyridine derivatives as mGluR2-negative allosteric modulators, compositions, and their use (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R<sup>1</sup>, R<sup>2</sup>, L, X<sub>1</sub>, X<sub>2</sub>, and X<sub>3</sub>, 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.</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="US10072003-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PRODRUG OF AMINO ACID DERIVATIVE (Fri, 27 Oct 2017)
Provided is an amino acid derivative prodrug represented by general formula (I-A) that is a prodrug form of an amino acid derivative which is a group 2 metabotropic glutamate receptor antagonist, or a pharmaceutically acceptable salt thereof. More specifically, provided is an amino acid derivative prodrug represented by general formula (I-A) that is a preventive or therapeutic drug for mood disorders (including depression and bipolar disorder), anxiety disorder, cognitive disorders, developmental disorders, Alzheimer's disease, Parkinson's disease, movement disorders associated with muscular rigidity, sleep disorders, Huntington's chorea, eating disorders, drug dependence, epilepsy, brain infarction, cerebral ischemia, cerebral insufficiency, cerebral edema, spinal cord disorders, head trauma, inflammation and immune- related diseases, and so on.
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SELECTIVE D3 DOPAMINE RECEPTOR AGONISTS AND METHODS OF THEIR USE (Fri, 20 Oct 2017)
The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.
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COMPOUNDS AND COMPOSITIONS FOR THE DETECTION AND TREATMENT OF ALZHEIMER'S DISEASE AND RELATED DISORDERS (Thu, 19 Oct 2017)
One aspect of the present invention relates to compounds of formula (II), compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.
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NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS (Fri, 13 Oct 2017)
Neuropeptide S receptor agonists are provided. The NPS agonists include trimeric, tetrameric, pentameric or hexameric peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The peptidomimetic molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.
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NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS (Fri, 13 Oct 2017)
Neuropeptide S receptor agonists are provided. The NPS agonists include peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.
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HETEROCYCLIC COMPOUND (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention provides a compound having an MAGL inhibitory action, and useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.45mm" wi="69.85mm" file="US20170283406A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as defined in the specification, or a salt thereof.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula Ia:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.46mm" wi="62.48mm" file="US20170283423A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metastases, gastrointestinal stromal tumors, and giant cell tumors.</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, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a process suitable for adoption to large scale manufacture of 1-isopropyl-3-{5-[1-(3-methoxypropyl)piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate of formula (I), which is a selective 5-HT<sub>4 </sub>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.</p>
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HETEROCYCLIC COMPOUND (Fri, 06 Oct 2017)
The present invention provides a compound having an MAGL inhibitory action, and useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates to a compound represented by the formula (I) : wherein each symbol is as defined in the specification, or a salt thereof.
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Pharmaceutical compounds and use of same in cancer and tauopathies (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (l)-(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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Dosing Regimens for Treating And/Or Preventing Cerebral Amyloidoses (Fri, 29 Sep 2017)
<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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ALKYLIDENE PHOSPHONATE ESTERS AS P-GLYCOPROTEIN INDUCERS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to the alkylidene phosphonate esters of formula I wherein, R<sub>1 </sub>is selected from a group consisting of hydrogen or alkyl group; R<sub>2 </sub>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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="52.24mm" file="US20170275314A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula I: R1-L1-C(A)(A′)-CH<sub>2</sub>, -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.</p>
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Allosteric modulators of nicotinic acetylcholine receptors (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.65mm" wi="69.85mm" file="US09840481-20171212-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Fri, 29 Sep 2017)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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Alzheimer's disease treatment medicine (Sat, 23 Sep 2017)
The invention discloses an Alzheimer's disease treatment medicine, which has a chemical structure represented by a formula (I). According to the present invention, after differentiated SH-SY5Y cells are treated for 48 h with 15 [mu]M beta-amyloid protein, the survival rate of the cells treated with a positive control group and the survival rate of the cells treated with the compound represented by the formula (I) can be significantly improved, and the survival rate of the cells treated with the compound represented by the formula (I) is superior to the survival rate of the cells treated with the positive control group, such that the compound represented by the formula (I) can provide the protection effect for the beta-amyloid protein induced SH-SY5Y cell injury, and can be developed as the Alzheimer's disease treatment medicine. The formula (I) is defined in the specification.
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Moringa seed total phenolic glycoside and application thereof to preparation of medicines and health-care products (Sat, 23 Sep 2017)
The invention relates to moringa seed total phenolic glycoside. The moringa seed total phenolic glycoside is prepared from main components including moringa phenolic glycoside A and moringa phenolic glycoside K, and the content sum is greater than 60 percent; the moringa seed total phenolic glycoside has the activities of resisting depression, resisting anxiety, resisting Alzheimer's disease, treating alcoholic chemical liver injuries, resisting inflammation and preventing and treating diabetes mellitus and headache. Compared with traditional Chinese herb extracts, the total phenolic glycoside provided by the invention has the advantages of definite components and definite active mechanism.
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Prodrug of 1,1′-(1,6-dioxo -1,6-hexanediyl)bis-D-proline (Fri, 22 Sep 2017)
<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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M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS AND METHODS OF USE THEREOF (Fri, 22 Sep 2017)
The present invention is directed to compounds of general formula (I) or pharmaceutically acceptable salts thereof, 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 compositions comprising the compounds, or pharmaceutically acceptable salts thereof, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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COMBINATION OF A BACE INHIBITOR AND AN ANTIBODY OR ANTIGEN-BINDING FRAGMENT FOR THE TREATMENT OF A DISORDER ASSOCIATED WITH THE ACCUMULATION OF AMYLOID BETA (Fri, 22 Sep 2017)
The present disclosure provides for methods for treating a subject having a disease or disorder associated with the accumulation of amyloid beta, comprising administering to the subject a BACE inhibitor and an antibody or antigen-binding fragment that binds to amyloid beta n-42. In some embodiments, the disease or disorder is Alzheimer's Disease.
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γ-diketones as Wnt/β-catenin signaling pathway activators (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.</p>
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Nitrogen-containing heterocyclic compound (Fri, 15 Sep 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="40.98mm" wi="54.02mm" file="US09789084-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, <br/> or a salt thereof. </p>
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S-imino-S-oxo iminothiazine compounds as bace inhibitors, compositions, and their use (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">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 R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2A</sup>, R<sup>2B</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>N</sup>, ring A, R<sup>A</sup>, m, ring B, R<sup>B</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.18mm" wi="61.89mm" file="US09957269-20180501-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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DETECTION OF NEURODEGENERATIVE DISEASES (Fri, 15 Sep 2017)
The present invention relates to novel compounds, their uses as biomarker, and/or methods including a non-invasive in vitro method using this biomarker, for diagnosing or monitoring the development or the progression of Alzheimer's disease (AD) or a disease or disorder associated with β-amyloid peptide (Aβ) deposition or tau hyperphosphorylation or a disease or disorder characterized by a proteinopathy implicating abnormalities in protein kinase C (PKC).
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QUINAZOLINE COMPOUNDS USEFUL AS M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 15 Sep 2017)
The present invention is directed to compounds of Formula (I): (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R7, R8, R9, R11, n and p are defined herein. The compounds of Formula (I) are M1 receptor positive allosteric modulators that are useful in the treatment of diseases in which the M1 receptor is involved, including Alzheimer's disease, schizophrenia, pain and sleep disorders. The invention also relates to pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, and to methods of using the compounds of Formula (I) in the treatment of diseases mediated by the M1 receptor.
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Heterocyclic compound for treating Alzheimer disease and preparation method thereof (Sat, 09 Sep 2017)
The invention relates to a heterocyclic compound for treating Alzheimer disease and a preparation method thereof. The heterocyclic compound has a good effect of inhibiting the activity of acetyl cholinesterase; as proved by a behavioral experiment research of a senescence-accelerated mouse (SAM-P/8), the heterocyclic compound can effectively improve the memory function of the SAM-P/8 mouse, so that the heterocyclic compound can be used for treating cognitive dysfunction and/or neural degeneration dementia with abnormal protein aggregation, particularly the Alzheimer disease.
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BACE 1 INHIBITORS (Sat, 09 Sep 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 compound of the present invention is useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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PIPERIDINE DERIVATIVE AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention provides N-[1-(1-Cyclohexyl-3,5-dimethyl-1H-pyrazole-4-sulfonyl)-4-phenyl-piperidin-4-ylmethyl]-N-isobutyl-4-{[(piperidin-4-ylmethyl)-amino]-methyl}-benzenesulfonamide and pharmaceutically acceptable salts thereof. These compounds may be useful in the treatment of diseases such as Alzheimer's disease or renal failure. The present invention further relates to methods for the preparation of compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the use of such compounds and/or pharmaceutical compositions in treating certain diseases.
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M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR COMPOUNDS AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention is directed to compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Q, X, Y, Z, R1, R7 and n are defined herein. The compounds of Formula (I) are M1 receptor positive allosteric modulators that are useful in the treatment of diseases in which the M1 receptor is involved, including Alzheimer's disease, schizophrenia, pain and sleep disorders. The invention also relates to pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, and to methods of using the compounds of Formula (I) in the treatment of diseases mediated by the M1 receptor.
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Therapeutic agent for Alzheimer's disease (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention aims to provide a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease, which has a novel action mechanism and shows less side effects. A polyphenol derivative having liposolubility enhanced by the introduction of at least one kind of a liposoluble group selected from the group consisting of a chain saturated hydrocarbon group, a chain unsaturated hydrocarbon group, a cyclic saturated hydrocarbon group, a cyclic unsaturated hydrocarbon group, an aromatic hydrocarbon group, a liposoluble vitamin residue and a sterol residue has an action to potentiate neprilysin activity, and is useful as a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease.</p>
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Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof (Fri, 08 Sep 2017)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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β- and γ-diketones and γ-hydroxyketones as <i>WNT</i>/β-catenin signaling pathway activators (Fri, 01 Sep 2017)
<p id="p-0001" num="0000">The present application discloses a compound which is</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.83mm" wi="54.02mm" file="US09884053-20180206-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> which activates Wnt/β-catenin signaling and thus treats or prevents diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases. </p>
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Diazine-fused amidines as BACE inhibitors, compositions, and their use (Fri, 01 Sep 2017)
<p id="p-0001" num="0000">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 R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2</sup>, R<sup>A</sup>, ring A, R<sup>A</sup>, m, L<sub>1</sub>, R<sup>L</sup>, ring C, R<sup>C</sup>, 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.50mm" wi="60.28mm" file="US09868738-20180116-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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DISRUPTION OF THE INTERACTION BETWEEN AMYLOID BETA PEPTIDE AND DIETARY LIPIDS (Fri, 01 Sep 2017)
The present invention relates to methods of treating neurodegenerative disorders associated with Alzheimer's disease (AD), Parkinson's disease (PD) and synucleinopathies, such as dementia with Lewy bodies, Down Syndrome (DS) and associated cognitive disorders, multiple system atrophy, and rare neuroaxonal dystrophies, such as Niemann-Pick type C disease (NPC) and Gaucher's disease comprising administering an inhibitor to disrupt the interaction between Αβ or αS and neuronal lipids. The invention further relates to assays for identifying agents that reduce interaction between Αβ or αS and neuronal lipids. Lastly, the invention relates to methods and compositions for intranasal administration of fatty acids or lipids containing fatty acid acyl chains of dietary lipids for promoting central nervous system health and/or prevention or treatment of neurodegenerative disorders.
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GLYCOSIDASE INHIBITORS (Fri, 01 Sep 2017)
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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GLYCOSIDASE INHIBITORS (Fri, 01 Sep 2017)
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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Glycosidase inhibitors (Fri, 01 Sep 2017)
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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Glycosidase inhibitors (Fri, 01 Sep 2017)
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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