Parkinson's disease

METHODS OF TREATMENT AND COMBINATION THERAPIES USING GCASE ACTIVATOR HETEROBICYCLIC AND RELATED COMPOUNDS (Fri, 10 Nov 2017)
The invention provides methods of treatment and combination therapies using heterobicyclic and related compounds that activate Gcase, such as in the treatment of endometriosis and Parkinson's disease. An exemplary heterobicyclic compound that activates Gcase is a substituted pyrrolo[1,2-a]pyrimidine compound, such as substituted 2,4-dimethyl-N-phenylpyrrolo[1,2-a]pyrimidine-8-carboxarnide compounds and variants thereof.
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SUBSTITUTED PYRROLO[1,2-α]TRIAZINES AND RELATED COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 10 Nov 2017)
The invention provides substituted pyrrolo[1,2-α]triazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]triazines compounds described herein include substituted 2,4-dimethyl-pyrrolo[1,2-α] [1,3,5]triazine-8-carboxamide compounds and variants thereof.
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SUBSTITUTED IMIDAZO[1,2-b]PYRIDAZINES, SUBSTITUTED IMIDAZO[1,5-b]PYRIDAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 10 Nov 2017)
The invention provides substituted imidazo[1,2-b]pyridazine compounds, substituted imidazo[1,5-b]pyridazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,2-b]pyridazine compounds described herein include substituted imidazo[1,2-b]pyridazine-3-carboxamide compounds and variants thereof.
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SUBSTITUTED IMDAZO[1,2-α]PYRIDINES, SUBSTITUTED IMIDAZO[1,2-α]PYRAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 10 Nov 2017)
The invention provides substituted imidazo[1,2-α]pyridine compounds, substituted imidazo[1,2-α]pyrazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary imidazo[1,2-α] pyridine compounds described herein include substituted 5-methyl imidazo[1,2-α]pyridine-8-carboxamide compounds and variants thereof.
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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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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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CARBIDOPA AND L-DOPA PRODRUGS AND METHODS OF USE (Fri, 27 Oct 2017)
The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.
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Heteroaryl compounds and methods of use thereof (Fri, 27 Oct 2017)
Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and neurological disorders, including, but not limited to, e.g., psychosis, schizophrenia, depression, movement disorders, and Parkinson's disease.
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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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PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 Oct 2017)
The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.
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IMIDAZO [1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 Oct 2017)
The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrirnidine-8-carboxamide compounds and variants thereof.
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PYRROLO[1,2-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 Oct 2017)
The invention provides substituted pyrrolo[1,2-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-pyrrolo[1,2-a]pyrimidine-8-carboxarnide compounds and variants thereof.
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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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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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DELTA OPIOID AGONIST, MU OPIOID ANTAGONIST COMPOSITIONS AND METHODS FOR TREATING PARKINSON'S DISEASE (Fri, 06 Oct 2017)
The present invention provides for compositions and methods for the treatment of Parkinson's disease comprising a compound of formula (i): or a pharmaceutically effective salt or ester thereof alone or in combination with L-DOPA to provide a synergistic effect, thereby providing methods of (1) treating patients with Parkinson's Disease for whom L-DOPA is no longer effective, (2) treating patients with Parkinson's Disease who developed dyskinesia due to L-DOPA, (3) treating patients with Parkinson's Disease who have are receiving deep brain stimulation and (4) treating patients with Parkinson's Disease whose symptoms interfere with activities of daily living.
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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="US20170275260A1-20170928-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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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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BICYCLIC COMPOUNDS FOR DIAGNOSIS AND THERAPY (Fri, 15 Sep 2017)
The present invention relates to the compounds of formula (I) that can be employed in the diagnosis, monitoring of disease progression or monitoring of drug activity, of a group of disorders and abnormalities associated with alpha-synuclein (a-synuclein, A- synuciein, aSynuciein, A-syn, a-syn, aSyn) aggregates including, but not limited to, Lewy bodies and/or Lewy neurites, such as Parkinson's disease. The instant compounds are particularly useful in determining a predisposition to such a disorder, monitoring residual disorder, or predicting the responsiveness of a patient who is suffering from such a disorder to the treatment with a certain medicament. The present compounds can also be used to treat, alleviate or prevent a disorder or abnormality associated with alpha-synuclein aggregates.
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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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Chemical model of a neurodegenerative disease, method for preparation and uses of same (Wed, 30 Aug 2017)
<p id="p-0001" num="0000">The invention concerns the use of pyridinium furosemide or one of the derivatives, analogs, salts, metabolites, or prodrugs thereof in the preparation of a chemical model of a neurodegenerative disease, preferably Parkinson's disease. The invention also concerns the corresponding chemical model and the uses of same, in particular in screening tests for identifying drug candidates.</p>
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N-Substituted-5-Substituted Phthalamic Acids as Sortilin Inhibitors (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention is directed to N-substituted-5-substituted phthalamic acids which of formula (A).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.73mm" wi="54.53mm" file="US20170239226A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds are considered useful for the treatment of diseases treatment of a neurodegenerative disease, psychiatric disease, motoneuron disease, peripheral neuropathies, pain, neuroinflammation or atherosclerosis such as Alzheimer's disease and Parkinson's disease.</p>
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PYRROLOQUINOLINE DERIVATIVES AS 5-HT6 ANTAGONISTS, PREPARATION METHOD AND USE THEREOF (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">This invention concerns pyrroloquinoline derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome. The compounds have the general formula (XIV), wherein the symbols have the meanings given in the description.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.83mm" wi="69.85mm" file="US20170239237A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS DERIVED FROM 3-ALKYLAMINO-1H-INDOLE ACRYLATE, AND THE USE THEREOF IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Thu, 24 Aug 2017)
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.
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8'-HYDROXY-DIHYDROERGOTAMINE COMPOUNDS AND COMPOSITIONS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">8′-Hydroxy-Dihydroergotamine (8′-OH DHE) medicinal compounds, compositions, and dosage forms containing such compositions are provided. Also provided herein are methods of treatment, prevention, or amelioration of diseases, conditions or disorders selected from amyotrophic lateral sclerosis (ALS), Parkinson's disease, stress/anxiety, nausea, emesis, aggression, pain, neuropathic pain, sleeplessness, insomnia, restless leg syndrome and depression using the compounds, compositions, dosage forms and administration techniques disclosed herein.</p>
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Nitrogen-containing heterocyclic compound (Fri, 04 Aug 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="40.39mm" wi="53.42mm" file="US09775827-20171003-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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6-MEMBERED AZA-HETEROCYCLIC CONTAINING DELTA-OPIOID RECEPTOR MODULATING COMPOUNDS, METHODS OF USING AND MAKING THE SAME (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present embodiments are directed, in part, to compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof for modulating the activity of delta opioid receptor, biased and/or unbiased, and/or methods for treating pain, migraines, headaches, depression, Parkinsons Disease, anxiety, and/or overactive bladder, and other disorders and conditions described herein or any combination thereof.</p>
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6,7,8,9-TETRAHYDRO-5H-PYRIDO[2,3-d]AZEPINE DOPAMINE D3 LIGANDS (Fri, 21 Jul 2017)
The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof wherein the variables R1, R2, R3, R4, R5, a and A are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D3-mediated (or D3-associated) disorders including, e.g., substance addiction, substance abuse, schizophrenia (e.g., its cognitive symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD or PD), Parkinson's disease, mania, anxiety, impulse control disorders, sexual disorders and depression.
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POSITIVE ALLOSTERIC MODULATORS OF THE GLP-1 RECEPTOR (Fri, 07 Jul 2017)
Described are positive allosteric modulators of the GLP-1 receptor, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for diabetes mellitus type 2, obesity, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, cognitive dysfunction, learning disability, and asthma in a subject.
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Substituted pyrazolo[1,5-a]pyrimidines and their use in the treatment of medical disorders (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The invention provides substituted pyrazolo[1,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidine compounds described herein include 5,7 -dimethyl-N-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide compounds and variants thereof.</p>
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Blood-Brain Barrier Shuttles Containing Antibodies Recognizing Alpha-Synuclein (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The invention provides blood-brain barrier shuttles comprising monoclonal antibody 5C1 and related antibodies linked to a monovalent binding entity for a blood-brain barrier receptor. The 5C1 antibody binds to an epitope within residues 118-126 of alpha-synuclein. The antibodies are useful, for example, for treating and/or diagnosing synucleinopathies including Lewy body diseases, such as Parkinson's disease, diffuse Lewy body disease (DLBD), Lewy body variant of Alzheimer's disease (LBV),</p> <p id="p-0002" num="0000">Alzheimer's and Parkinson's disease comorbidity, and pure autonomic failure, as well as multiple system atrophy (MSA).</p>
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Organosulfur compounds for the prevention and treatment of neurodegenerative diseases (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Organosulfur compounds and compositions are disclosed which can be administered in order to provide protection from the formation of aldehyde-protein adducts, protein aggregates, and the resulting neuroinflammation. Various neurodegenerative diseases which are suitable for treatment using these compositions include Alzheimer's disease, senile dementia, Parkinson's disease, multiple sclerosis, Lewy body disease, peripheral neuropathy, spinal cord injury, traumatic brain injury, stroke and cerebral ischemia.</p>
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PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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Compositions and methods for treating neurodegenerative diseases (Fri, 23 Jun 2017)
<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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WATER-SOLUBLE DERIVATIVES OF 3,5-DIPHENYL-DIAZOLE COMPOUNDS (Fri, 23 Jun 2017)
The present invention is concerned with derivatives of 3,5-diphenyl-diazole derivatives, which are effective therapeutic agents for use in treating diseases linked to protein aggregation and/or neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD). and Transmissible spongi form encephalopathies (TSEs) such as Creutzfeldt- Jakob disease CJD). Formula :(I) The therapeutic effect is caused by the inhibition of the protein aggregation in the affected tissue, such as the brain, 3,5-Diphenyl-diazole derivatives have been shown to be effective in inhibiting aggregation of proteins but arc also characterized by their poor solubility in aqueous solutions. The prodrugs of the invention are modified 3,5-diphenyl-diazole derivatives, which are characterized by their improved solubility in aqueous solutions, and by their increased bioavailability.
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NOVEL BICYCLIC-COMPOUNDS FOR USE AS A MEDICAMENT, IN PARTICULAR FOR TREATMENT OF PARKINSON'S DISEASE (Fri, 23 Jun 2017)
The invention relates to novel small molecule compounds having a basic structure as depicted by formula (A), where in particular exemplary embodiments R1 is -OH, R2 is -NO2 and R3 is H, R4 and R5 are H, one of R6 and R7 is selected from H, -CONH2, and -CONR92, and the other one is selected from -CONR92 and -CONR11R9, wherein R9 and R11 are (possibly multiply) substituted alkyl and H or alkyl, respectively. The compounds of the invention inhibit the enzyme Catechol-O-methyltransferase (COMT) and exhibit a low off- target profile. The compounds are provided for use as a medicament, in particular for use in prevention or treatment of Parkinson's disease.
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PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF (Fri, 23 Jun 2017)
The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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SPIROIMIDAZOLE COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Thu, 08 Jun 2017)
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 Aß-related pathologies such as Down's syndrome, ß- amyloid angiopathy such as, but not limited to, cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
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GLYCOLIPIDS AS TREATMENT FOR DISEASE (Thu, 08 Jun 2017)
This invention provides compounds, compositions, and methods for treating a disorder selected from cancer, hyperinsulinemia, hypoglycemia, hyperinsulinemia with hypoglycemia, atypical Parkinson's disease, Huntington's disease, mutliple systems atrophy, GM3 synthase deficiency, GM2 synthase deficiency or tauopathy.
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ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF (Fri, 02 Jun 2017)
<p id="p-0001" num="0000">Disclosed are compounds of Formula (IVA), or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof: Formula (IVA), wherein “R<sup>Ia</sup>”, “R<sup>Ib</sup>”, “R<sup>Ic</sup>”, “R<sup>Id</sup>”, “R<sup>Ie</sup>”, are defined herein above, which compounds are believed suitable for use in positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) receptors, for example, those found in the cerebral cortex and the hippocampus. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Alzheimer's disease (AD), schizophrenia, and Parkinson's disease (PD), or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.61mm" wi="62.40mm" file="US20170152221A1-20170601-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Inhibitors of LRRK2 kinase activity (Fri, 02 Jun 2017)
The present invention provides compounds having a structure according to Formula I: or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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CRYSTALLINE FORMS AND PROCESSES FOR THE PREPARATION OF CANNABINOID RECEPTOR MODULATORS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB<sub>2 </sub>receptor and are therefore useful in the treatment of CB<sub>2 </sub>receptor-mediated disorders, for example, osteoarthritis; pain; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation for example; atherosclerosis; undesired immune cell activity, and inflammation associated with a disorder selected from: osteoarthritis, anaphylaxis, Behcet's disease, graft rejection, vasculitis, gout, spondylitis, viral disease, bacterial disease, lupus, inflammatory bowel disease, autoimmune hepatitis, and type 1 diabetes mellitus; 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.</p>
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HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (1)-(11 1) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.</p>
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Nitrogen-containing heterocyclic compound (Wed, 24 May 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="40.64mm" wi="53.51mm" file="US09655881-20170523-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Fri, 05 May 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 a medicament such 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, and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.52mm" wi="58.59mm" file="US20170121308A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the attached DESCRIPTION.</p>
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Compositions and methods for prevention and treatment of brain diseases and conditions (Fri, 05 May 2017)
Disclosed herein are compounds, extracts, and active fractions of the plant Geumjaponicum and methods for preventing or treating brain diseases or conditions, such as ischemic stroke, Alzheimer's disease, vascular dementia, mild cognitive impairment (MCI), chronic cerebral ischemia and Parkinson's disease. The compounds provided herein can be formulated into pharmaceutical compositions and medicaments that are useful in the disclosed methods. Also provided are the use of the compounds and extracts in preparing pharmaceutical formulations and medicaments.
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Compositions and methods for prevention and treatment of brain diseases and conditions (Fri, 05 May 2017)
Disclosed herein are compounds, extracts, and active fractions of the plant Geumjaponicum and methods for preventing or treating brain diseases or conditions, such as ischemic stroke, Alzheimer's disease, vascular dementia, mild cognitive impairment (MCI), chronic cerebral ischemia and Parkinson's disease. The compounds provided herein can be formulated into pharmaceutical compositions and medicaments that are useful in the disclosed methods. Also provided are the use of the compounds and extracts in preparing pharmaceutical formulations and medicaments.
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NURR1:RXR ACTIVATING COMPOUNDS FOR SIMULTANEOUS TREATMENT OF SYMPTOMS AND PATHOLOGY OF PARKINSON'S DISEASE (Fri, 28 Apr 2017)
The invention provides a series of substituted aryl pyrimidine compounds and the use of these compounds as therapeutics to treat or prevent neurodegenerative disorders, including Parkinson's disease. Compounds of the invention are also able to treat the symptoms of such diseases and therefore represent a new treatment modality for ameliorating chronic and acute conditions. The compounds of the invention are capable of selectively potentiating the activity of the Nurr1:RXRα heterodimer, and are able to treat diseases or conditions associated with aberrant Nurr1:RXRα function. The invention further provides methods for treating neurodegenerative disorders by administration of Nurr1:RXRα activating agents.
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CRYSTALLINE FORM OF 2-(2,6-DICHLOROPHENYL)-1-[(1S,3R)-3-(HYDROXYMETHYL)-5-(3-HYDROXY-3-METHYLBUTYL)-1-METHYL-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]ETHANONE FOR THE TREATMENT OF PARKINSON'S DISEASE (Fri, 28 Apr 2017)
The invention provides a crystalline form of 2-(2,6-dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone, and pharmaceutical compositions thereof. The invention further provides methods of using a crystalline form of 2-(2,6-dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone to treat cognitive impairment associated with Parkinson's disease or schizophrenia.
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PHENYL-SUBSTITUTED NICOTINIC LIGANDS, AND METHODS OF USE THEREOF (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">Disclosed are compounds and methods of using them to treat a disorder selected from the group consisting of addiction, pain, obesity, schizophrenia, epilepsy, mania and manic depression, anxiety, Alzheimer's disease, learning deficit, cognition deficit, attention deficit, memory loss, Lewy Body Dementia, Attention Deficit Hyperactivity Disorder (ADHD), Parkinson's disease, Huntington's disease, Tourette's syndrome, amyotrophic lateral sclerosis, inflammation, stroke, spinal cord injury, dyskinesias, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, autism, mutism, trichotillomania, hypothermia, and disorders of sleep.</p>
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Magnesium compositions and uses thereof for neurological disorders (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">A composition for administration to a subject, such as oral administration to a subject, for example, has been provided. Such a composition may comprise at least one magnesium-counter ion compound. A magnesium-counter ion composition described herein may be useful for any of a variety of applications provided herein, such as maintaining, enhancing, and/or improving health, nutrition, and/or another condition of a subject, and/or cognitive, learning, and/or memory function. A magnesium-counter ion composition provided herein may be useful for administration to a subject presenting magnesium deficiency, mild cognitive impairment, Alzheimer's disease, attention deficit hyperactivity disorder, ALS, Parkinson's disease, diabetes, migraine, anxiety disorder, mood disorder, and/or hypertension. A kit, method, and other associated technology are also provided.</p>
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NOVEL COMPOUNDS ADVANTAGEOUS IN THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS (Fri, 21 Apr 2017)
A series of novel amides showing broad pharmaceutical activity. Compounds described herein are effective as anticonvulsants, chemical countermeasures, and analgesics. Such compounds also show, neuroprotective/neuroreparative effects and activity against spinal muscular atrophy. Such pharmaceutically active compounds show utility in the treatment of central nervous system ("CNS") diseases and disorders, such as anxiety, depression, insomnia, migraine headaches, schizophrenia, neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's, ALS, and Huntington's disease) spasticity, and bipolar disorder. Furthermore, such compounds may additionally find utility as analgesics (e.g., for the treatment of chronic or neuropathic pain) and as neuroprotective agents useful in the treatment of stroke(s), and/or traumatic brain and/or spinal cord injuries.
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Thu, 20 Apr 2017)
The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as a medicament such 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, and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof. wherein each symbol is as described in the attached DESCRIPTION.
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Fri, 14 Apr 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.74mm" wi="53.76mm" file="US20170100384A1-20170413-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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PROTECTED FUMARIC ACID-BASED METABOLITES FOR THE TREATMENT OF AUTOIMMUNE DISEASES (Fri, 14 Apr 2017)
The present invention provides novel cell-permeable fumarate acyl mercaptoethylamines (FAMs) which have cellular effects including induction of Nrf2 and inhibition of the NFkB pathway. These compounds have utility in medicine including their use in treatment of diseases such as Multiple sclerosis, Non-alcoholic Steatohepatitis, Psoriasis, Inflammatory Arthritis, Inflammatory Bowel Disease, Asthma, Chronic Obstructive Pulmonary Disease, Cancer, Parkinson's Disease, Alzheimer's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis.
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BIARYL KINASE INHIBITORS (Fri, 07 Apr 2017)
The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.
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BIARYL KINASE INHIBITORS (Fri, 07 Apr 2017)
The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.
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Pro-Neurogenic Compounds (Fri, 07 Apr 2017)
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.
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AMANTADINE NITRATE COMPOUND HAVING A NEUROPROTECTIVE EFFECT AND PREPARATION AND MEDICAL USE THEREOF (Thu, 06 Apr 2017)
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). 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.
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COMPOSITIONS COMPRISING TRITERPENOIDS (Fri, 31 Mar 2017)
The invention relates to compositions and formulations comprising at least one triterpenoic acid and at least one neutral triterpenoid and uses thereof for treating for use in treating a condition selected from Alzheimer's disease (AD), Parkinson's Diseases (PD) and vascular dementia (VD).
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IMIDAZOPYRIDINE COMPOUNDS AND THEIR USE AS 5-HT6 RECEPTOR LIGANDS (Fri, 31 Mar 2017)
Novel imidazo[4,5-c]pyridine and imidazo[4,5-b]pyridine derivatives of formula (I) as antagonists of 5-HT6 receptors, particularly for use in the prevention or treatment of schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, neuropathic pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome.
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2,3,4,5-TETRAHYDROPYRIDIN-6-AMINE DERIVATIVES (Fri, 31 Mar 2017)
The present invention relates to 2,3,4,5-tetrahydropyridin-6-amine compound inhibitors of beta-secretase having the structure shown in Formula (I) wherein the radicals are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, or dementia associated with beta-amyloid.
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NOVEL IMIDAZO [4,5-C] QUINOLINE AND IMIDAZO [4,5-C][1,5] NAPHTHYRIDINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 24 Mar 2017)
The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R1, R1a, R1b, 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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1-PHENYLPYRROLIDIN-2-ONE DERIVATIVES AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, R6, R7, X and Y 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/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, 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.
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TRIAZOLONE COMPOUNDS AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z 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, as Alzheimer's disease, neuropathic pain, 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, 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.
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IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK (Fri, 24 Mar 2017)
The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, 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, 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.
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NOVEL COMPOSITIONS FOR PREVENTING AND/OR TREATING DEGENERATIVE DISORDERS OF THE CENTRAL NERVOUS SYSTEM (Thu, 23 Mar 2017)
The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Thu, 23 Mar 2017)
The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as medicaments such 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, and the like. The present invention relates to a compound represented by the formula (I) wherein ring A is an optionally substituted 5- or 6-membered ring; R is a C 1-6 alkyl group substituted by 1 to 5 halogen atoms; and X is -CH= or -N=, or a salt thereof.
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Novel Imidazo[4,5-c]Quinoline And Imidazo[4,5-c][1,5]Naphthyridine Derivatives As LRRK2 Inhibitors (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.02mm" wi="58.34mm" file="US20170073343A1-20170316-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>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, 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.</p>
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CYCLOALKYL-HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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HETEROBICYCLIC PYRIMIDINONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 10 Mar 2017)
The invention provides heterobicyclic pyrimidinone compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary heterobicyclic pyrimidinone compounds described herein include 6-oxo-3,4-dihydro-2H,6H-pyrimido[2,1-b)][1,3]thiazine-7-carboxamide compounds.
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THIAZOLO(3,2-A) PYRIMIDINONE AND OTHER HETEROBICYCLIC PYRIMIDINONE COMPOUNDS FOR USE IN MEDICAL THERAPY (Fri, 10 Mar 2017)
The invention provides heterobicyclic pyrimidinone compounds such as thiazolo[3,2-a]pyrimidinone compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary heterobicyclic pyrimidinone compounds described herein include 5-oxo- 2,3-dihydro-5H-hiazolo[3,2-a]pyrimidine-6-carboxarnide compounds.
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DISRUPTION OF THE INTERACTION BETWEEN AMYLOID BETA PEPTIDE AND DIETARY LIPIDS (Fri, 10 Mar 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 aS and neuronal lipids. The invention further relates to assays for identifying agents that reduce interaction between Αβ or aS 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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A PRODUCTION METHOD OF 1-(4-FLUOROBENZYL)-3-(4-ISOBUTOXYBENZYL)-1-(1-METHYLPIPERIDIN- 4— YL)UREA AND ITS DEUTERATED ANALOGS NOT CONTAINING DIMERIC IMPURITIES (Fri, 10 Mar 2017)
The invention relates to an improved production method of 1-(4-fluorobenzyl)-3-(4-- isobutoxybenzyl)-1-(1— methylpiperidin-4-yl)urea of formula I, known under the generic name of pimavanserin. The method consists of two steps, namely a reaction of N-(4- fluorobenzyl)-l-methylpiperidine-4-amine with cyanic acid, the next step being a reaction of the obtained compound from the first step, 1-(4-fluorobenzyl)-1-(1-methylpiperidin-4-yl)urea and 4-isobutoxybenzaldehyde or with its precursors. Pimavanserin is an inverse agonist of the serotonin 5-HT2A receptor and is currently in the tartrate form in stage III of clinical trial for the treatment of psychosis in patients suffering from Parkinson's disease and has potential to become part of the therapy of other psychotic conditions.
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NOVEL FYN KINASE INHIBITORS (Fri, 10 Mar 2017)
The present invention relates to the novel therapies to treat neurodegenerative diseases such as Parkinson's disease (PD). The present invention relates to novel small molecule inhibitors of Fyn Kinase and for testing activity against Parkinsons's disease models compounds that inhibit Fyn kinase having the following formula. (I)
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF PARKINSON'S DISEASE (Fri, 10 Mar 2017)
The invention relates to the compounds of formula I, formula II and formula III or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II and formula III, and methods for treating or preventing Parkinson's diseasemay be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment or management of Parkinson's diseasesuch as Parkinson's disease, scleroderma, restless leg syndrome, hypertension and gestational hypertension.
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6-MEMBERED AZA-HETEROCYCLIC CONTAINING DELTA-OPIOID RECEPTOR MODULATING COMPOUNDS, METHODS OF USING AND MAKING THE SAME (Fri, 10 Mar 2017)
The present embodiments are directed, in part, to compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof for modulating the activity of delta opioid receptor, biased and/or unbiased, and/or methods for treating pain, migraines, headaches, depression, Parkinsons Disease, anxiety, and/or overactive bladder, and other disorders and conditions described herein or any combination thereof.
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HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.54mm" wi="59.77mm" file="US20170057947A1-20170302-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 D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCl, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, bipolar disorder, chronic apathy, anhedonia, chronic fatigue, post-traumatic stress disorder, seasonal affective disorder, social anxiety disorder, post-partum depression, serotonin syndrome, substance abuse and drug dependence, drug abuse relapse, Tourette's syndrome, tardive dyskinesia, drowsiness, excessive daytime sleepiness, cachexia, inattention, sexual dysfunction, migraine, SLE, hyperglycemia, atherosclerosis, dislipidemia, obesity, diabetes, sepsis, post-ischemic tubular necrosis, renal failure, hyponatremia, resistant edema, narcolepsy, hypertension, congestive heart failure, postoperative ocular hypotonia, sleep disorders, and pain.</p>
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BRAIN-PENETRANT CHROMONE OXIME DERIVATIVE FOR THE THERAPY OF LEVODOPA-INDUCED DYSKINESIA (Fri, 03 Mar 2017)
The present invention provides a chromone oxime derivative of formula (I), which is a modulator of nervous system receptors sensitive to the neuroexcitatory amino acid glutamate and presents an advantageously high brain exposure upon oral administration, for the treatment or prevention of levodopa-induced dyskinesia. The present invention also provides an improved therapy of Parkinson's disease, using the chromone oxime derivative of formula (I) in combination with ievodopa.
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ISOINDOLINE-1-ONE DERIVATIVES AS CHOLINERGIC MUSCARINIC M1 RECEPTOR POSITIVE ALLOESTERIC MODULATOR ACTIVITY FOR THE TREATMENT OF ALZHEIMERS DISEASE (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof. (I) wherein each symbol is as described in the specification, or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.12mm" wi="69.85mm" file="US20170044143A1-20170216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Heterocyclic compounds and their use as dopamine D1 ligands (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">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 D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.46mm" wi="60.96mm" file="US09745317-20170829-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 17 Feb 2017)
A compound of Formula (I) is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula (I) as TD02 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula (I).
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TROPINOL ESTERS AND RELATED COMPOUNDS TO PROMOTE NORMAL PROCESSING OF APP (Fri, 17 Feb 2017)
The present invention relates to a method of mitigating in a mammal one or more symptoms associated with a disease characterized by amyloid, in particular beta-amyloid, deposits in the brain, or delaying or preventing the onset of said symptoms, said method comprising: administering one or more compounds selected from defined tropinol esters and related quinuclidine esters. Said amyloidogenic diseases include Alzheimer's disease, cognitive impairment, age-related macular degeneration (AMD), cerebrovascular dementia, Parkinson's disease, Huntington's disease, and cerebral amyloid angiopathy. The present invention further relates to a method of promoting the processing of amyloid precursor protein (APP) by the non-amyloidogenic pathway as characterized by increasing sAPPa and/or the sAPPa/A42 ratio in a mammal, and a method of inhibiting the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) in a mammal, via the administration of said defined tropinol esters and related quinuclidine ester compounds Fig. IA Fig. l B
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2,5-Disubstituted-Pyridyl Nicotinic Ligands, and Methods of Use Thereof (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">Disclosed are heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. The compounds are useful for treating a mammal suffering from any one of a range of therapeutic indications, including Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism, trichotillomania, and hypothermia.</p>
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HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">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 D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.04mm" wi="61.13mm" file="US20170037049A1-20170209-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">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 D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.46mm" wi="60.71mm" file="US20170037053A1-20170209-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.23mm" wi="69.85mm" file="US20170029417A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.57mm" wi="53.76mm" file="US09675597-20170613-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Feb 2017)
The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Thu, 02 Feb 2017)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein X, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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COMPOUNDS (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).</p>
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ANTI-NEUROINFLAMMATORY AND PROTECTIVE COMPOUNDS IN ACHILLEA FRAGRANTISSIMA (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">The invention relates to 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TIF) and achillolid A in prevention or treatment of Alzheimer's disease as well as other neurodegenerative diseases such as Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), ischemia, immunodeficiency virus-1 (HTV-1)-associated dementia, Lewy body associated dementia, traumatic brain injury (TBI), glioma, epilepsy. Huntington's disease, multiple sclerosis, glaucoma and schizophrenia where neuroinflammation, oxidative stress, glutamate toxicity and amyloid beta toxicity are part of the pathophysiology.</p>
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PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Isolated or pure compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including but not limited to psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing an isolated or pure compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.</p>
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Arylpyrrolopyridine derived compounds as LRRK2 inhibitors (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">The present invention is directed to arylpyrrolopyridine derivatives of Formula A:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="56.64mm" file="US09675594-20170613-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Lewy body dementia, Parkinson's disease or cancer.</p>
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BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABA<sub>A </sub>receptor agonist (e.g., a α5-containing GABA<sub>A </sub>receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction.</p>
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COMPOUNDS (Fri, 27 Jan 2017)
Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Thu, 26 Jan 2017)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein A, X, R 1 , R 2 , R 3 and R 4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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2-(PHENYL OR PYRID-3-YL) AMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE (Thu, 26 Jan 2017)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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COMPOUNDS (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).</p>
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SUBSTITUTED AMINOQUINAZOLINE COMPOUNDS AS A2A ANTAGONIST (Fri, 20 Jan 2017)
Provide the compound of generic formula I: The compound can be useful as A2A-receptor antagonist. Use the compound for the preparation of a medicament for the treatment and/or prevention of diseases associated with inhibiting the receptor, which includes central nervous system disorders such as Parkinson's disease. Pharmaceutical compositions which include an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier are also provided.
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SUBSTITUTED AMINOQUINAZOLINE COMPOUNDS AS A2A ANTAGONIST (Fri, 20 Jan 2017)
The present invention is directed to compounds of generic formula (I): or pharmaceutically acceptable salts thereof that are believed to be useful as an A2A-receptor antagonist. The invention is further directed to methods of treating a patient (preferably a human) for diseases or disorders in which the A2A-receptor is involved. The invention further involves use of the compounds as an A2A-receptor antagonist and/or inhibitor for the preparation of a medicament for the treatment and/or prevention of diseases associated with inhibiting the receptor, which includes central nervous system disorders such as Parkinson's disease. The invention is also directed to pharmaceutical compositions which include an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, 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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THERAPEUTIC COMPOUNDS (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.</p>
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PYRIDAZIN-3(2H)-ONE DERIVATIVES WHICH ARE SELECTIVE INHIBITORS OF THE ISOFORM B OF MONOAMINE OXIDASE (Thu, 12 Jan 2017)
The present invention refers to pyridazin-3(2H)-one derivatives of general structure I, II and III, which are selective MAO-B inhibitors, and to the use thereof for preparing pharmaceutical compositions intended to treat disorders derived from MAO-B hyperactivity, particularly degenerative disorders of the central nervous system (CNS), such as Parkinson's disease (PD), Alzheimer's disease (AD) and other dementias. These are pyridazin-3(2H)-one derivatives having dithiocarbamate moieties bonded to position 4, 5 or 6 through an alkyl chain of variable length (n=1, 2, 3). This invention is also directed to the preparation of said compounds.
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SUBSTITUTED QUINAZOLINE COMPOUNDS AND USES THEREOF FOR MODULATING GLUCOCEREBROSIDASE ACTIVITY (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">Disclosed are new small molecules having a substituted quinazoline core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules or activated glucocerebrosidase conjugated to the small molecules, which compositions may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease.</p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US20170001994A1-20170105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 inhibitors (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention provides novel 3,4-disubstituted-1H-pyrrolo[2,3-b]pyridine derivatives and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazine derivatives of Formula I, and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.94mm" wi="54.53mm" file="US09695171-20170704-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and X are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy. </p>
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Substituted 4-methyl-pyrrolo[1,2-A]pyrimidine-8-carboxamide compounds and uses thereof for modulating glucocerebrosidase activity (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">Disclosed are new small molecules having a 4-methylpyrrrolo[1,2-a]pyrimidine-8-carboxamide core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.</p>
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BICYCLIC HETEROCYCLIC COMPOUNDS AS PDE2 INHIBITORS (Fri, 06 Jan 2017)
The present invention is directed to dihydropyrazolopyrimidinone compounds of formulas (I) and (II) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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SUBSTITUTED TRIAZOLO BICYCLICCOMPOUNDS AS PDE2 INHIBITORS (Fri, 06 Jan 2017)
The present invention is directed to substituted triazolo bicycliccompounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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SUBSTITUTED TRIAZOLO BICYCLIC COMPOUNDS AS PDE2 INHIBITORS (Fri, 06 Jan 2017)
The present invention is directed to substituted triazolo bicyclic compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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BICYCLIC HETEROCYCLIC COMPOUNDS AS PDE2 INHIBITORS (Fri, 06 Jan 2017)
The present invention is directed to dihydropyrazolopyrimidinone compounds of formulas (I) and (II) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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SUBSTITUTED QUINAZOLINE COMPOUNDS AND USES THEREOF FOR MODULATING GLUCOCEREBROSIDASE ACTIVITY (Fri, 06 Jan 2017)
Disclosed are new small molecules having a substituted quinazoline core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules or activated glucocerebrosidase conjugated to the small molecules, which compositions may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher' s disease and Parkinson's disease.
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SUBSTITUTED 4-METHYL-PYRROLO[1.2-A]PYRIMIDINE-8-CARBOXAMIDE COMPOUNDS AND USES THEREOF FOR MODULATING GLUCOCEREBROSIDASE ACTIVITY (Fri, 06 Jan 2017)
Disclosed are new small molecules having a 4-methylpyrrrolo[l,2-a]pyrimidine- 8-carboxamide core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.
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Novel anti-neurodegenerative natural compounds isolated from Alpiniae Oxyphyllae Fructus and their total synthesis (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">This invention is directed to novel compounds isolated or derived from Alpiniae oxyphyllae fructus, chemically synthesized novel compounds, methods of preparing the novel compounds and uses thereof as neuroprotectants or drugs for treating neurodegenerative diseases such as Parkinson's disease.</p>
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HETEROCYCLIC COMPOUND (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.18mm" wi="69.85mm" file="US20160376244A1-20161229-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the attached DESCRIPTION.</p>
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2,3-DIHYDRO-4H-1,3-BENZOXAZIN-4-ONE DERIVATIVES AS MODULATORS OF CHOLINERGIC MUSCARINIC M1 RECEPTOR (Fri, 30 Dec 2016)
The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof: wherein each symbol is as defined in the attached DESCRIPTION.
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SUBSTITUTED PYRAZOLO/IMIDAZOLO BICYCLIC COMPOUNDS AS PDE2 INHIBITORS (Fri, 30 Dec 2016)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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METHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN AGGREGATION (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a <i>Caenorhabditis elegans </i>model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.</p>
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PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds (referred to herein as “PPDA compounds”) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.</p>
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Carbidopa And L-Dopa Prodrugs And Methods Of Use (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.</p>
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Pro-Neurogenic Compounds (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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Amantadine nitrate compound having a neuroprotective effect and preparation and medical use thereof (Fri, 16 Dec 2016)
The present invention relates to an amantadine nitrate compound having a neuroprotective effect and a preparation and a medical use thereof. The compound has the structure of the general formula (I). The compound has multiple mechanisms of action, comprising inhibiting DNA receptors, releasing NO, inhibiting calcium influxes, and having a better protective effects on cells, in particular neurocytes. The compound can be used for preparing a medicament having a cellular protective effect, which is used for preventing or treating diseases relevant to NMDA receptors, the elevation of the calcium anion in cells and the like, e.g. diseases relevant to neurodegeneration, comprising Alzheimer's disease, Parkinson's disease, cerebral paralysis, glaucoma and the like, and diseases relevant to the cardio-cerebral-vascular system, such as Parkinson's syndrome combined with cerebral arteriosclerosis, as well as preventing or treating respiratory tract infectivity caused by the influenza virus.
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Solid Forms Comprising(-)-O-Desmethylvenlafaxine And Uses Thereof (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Solid forms comprising a compound useful in the treatment, prevention and management of various conditions and diseases are provided herein. In particular, the invention provides solid forms comprising (−)-O-desmethylvenlafaxine, including salts thereof, having utility for the treatment, prevention and management of conditions and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.</p>
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6-ALKYL DIHYDROPYRAZOLOPYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 09 Dec 2016)
The present invention is directed to 6-alkyl dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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DIHYDROPYRAZOLOPYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 09 Dec 2016)
The present invention is directed to dihydropyrazolopyrimidinonecompounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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A NOVEL NEUROPROTECTIVE AND NEURORESTORATIVE N-PROPARGYL CAFFEAMIDE (PACA) AND USE AS A TREATMENT FOR NEURODEGENERATIVE DISEASES (Fri, 09 Dec 2016)
The present invention is directed to compounds, pharmaceutical compositions, and related methods of treatment and/or prevention for neurodegenerative diseases, such as Parkinson's disease.
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6-ALKYL DIHYDROPYRAZOLOPYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 09 Dec 2016)
The present invention is directed to 6-alkyl dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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SMALL MOLECULE ANALOGS OF THE NEMO BINDING PEPTIDE (Fri, 09 Dec 2016)
The invention is directed to a method of inhibiting, within a living cell, the interaction between NF-κB essential modulator ("NEMO") with IκB kinase-β (IKK-β) at the NEMO binding domain (NBD), comprising exposing the cell to an effective amount or concentration of a compound of the invention, a NEMO-binding domain analog (NBDA). The invention is further directed to a method of treating a condition in a patient, wherein inhibiting the interaction between NF-κB essential modulator ("NEMO") with IκB kinase-β (IKK-β) at the NEMO binding domain (NBD) is medically indicated, comprising administering to the patient an effective dose of a compound of the invention. Conditions that can be treated by a method of the invention includes muscular dystrophy, asthma, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, arthritis, diabetes, graft versus host disease, accelerated aging, heart ischemia, cancer, UV-induced skin damage, or an age-related pathology.
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DIHYDROPYRAZOLOPYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 09 Dec 2016)
The present invention is directed to dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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3-(6-CHLORO-3-OXO-3,4-DIHYDRO-(2H)-1,4-BENZOXAZIN-4-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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3-(5-CHLORO-2-OXO-2,3-DIHYDRO-1,3-BENZOTHIAZOL-3-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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Isoindoline-1-one derivatives as cholinergic muscarinic M1 receptor positive alloesteric modulator activity for the treatment of Alzheimers disease (Fri, 02 Dec 2016)
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. The present invention relates to a compound represented by the formula (I) or a salt thereof. (I) wherein each symbol is as described in the specification, or a salt thereof.
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PYRIMIDINONE AMIDE COMPOUNDS AS PDE2 INHIBITORS (Fri, 25 Nov 2016)
The present invention is directed to pyrimidinone amide compounds which may be useful as therapeutic agents for the treatment of central nervous system and/or peripheral disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Alzheimer's, cognitive impairment, anxiety, depression, migraines, or Huntington's disease, Parkinson's disease, Parkinson's disease dementia (PDD), and other diseases associated with striatal hypofunction or basal ganglia dysfunction.
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PYRIMIDINONE AMIDE COMPOUNDS AS PDE2 INHIBITORS (Fri, 25 Nov 2016)
The present invention is directed to pyrimidinone amide compounds which may be useful as therapeutic agents for the treatment of central nervous system and/or peripheral disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Alzheimer's, cognitive impairment, anxiety, depression, migraines, or Huntington's disease, Parkinson's disease, Parkinson's disease dementia (PDD), and other diseases associated with striatal hypofunction or basal ganglia dysfunction.
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HETEROARYL-PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 11 Nov 2016)
The present invention is directed to substituted pyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Cyclopropanamine compound and use thereof (Fri, 11 Nov 2016)
The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.
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3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL) PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">A compound of formula (I) or a salt thereof are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="57.40mm" file="US20160318884A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, X and R<sup>3 </sup>are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.</p>
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4-(piperrazin-1-yl)-pyrrolidin-2-one compounds as monoacylglycerol lipase (MAGL) inhibitors (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention aims to provide a compound having an MAGL inhibitory action, and useful as a prophylactic or therapeutic agent for neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis and the like), anxiety disorder, pain (e.g., inflammatory pain, carcinomatous pain, nervous pain and the like), epilepsy and the like. The present invention relates to a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.19mm" wi="69.85mm" file="US09624170-20170418-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the DESCRIPTION, or a salt thereof. </p>
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Glycolipids and pharmaceutical compositions thereof for use in therapy (Fri, 04 Nov 2016)
A compound of Formula I: R1 -L1 -C(A)(A') - CH<sb>2</sb>, - 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, muscie 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 aikenyl 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.
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SELECTIVE CALCIUM CHANNEL ANTAGONISTS (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to compositions and methods for the treatment and/or prevention of neurodegenerative disorders, e.g., Parkinson's disease (PD). In particular, the present invention provides compositions comprising selective antagonists of calcium ion channels (e.g., cav1.3-type ion channels), and methods of use thereof to treat or prevent neurodegenerative disorders.</p>
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Cyclopropanamine compound and use thereof (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US09714241-20170725-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as defined in the present specification, or a salt thereof. </p>
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Cyclopropanamine compound and use thereof (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="US09718814-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as defined in the present specification, or a salt thereof. </p>
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COMPOUNDS AND THEIR USE AS BACE1 INHIBITORS (Fri, 28 Oct 2016)
The present invention relates to compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, Y, Z, Q, W, m, u, ring (A), R2, R3, R4, R5 and R6, are as defined in the specification and claims. The present invention provides a pharmaceutical composition containing the compounds of Formula (I) and a therapeutic method of treating and/or preventing Downs syndrome, β-amyloid angiopathy, disorders associated with cognitive impairment, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegenerative diseases, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, Alzheimer's disease and/or Down syndrome, age-related macular degeneration (AMD), glaucoma, olfactory function impairment, traumatic brain injury, progressive muscle diseases, Type II diabetes mellitus and cardiovascular diseases (stroke).
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PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS (Fri, 28 Oct 2016)
Isolated or pure compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including but not limited to psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing an isolated or pure compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
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3,4-dihydroisoquinolin-2(1H)-yl compounds (Fri, 28 Oct 2016)
The invention provides certain 3,4-dihydroisoquinolin-2(1H)-yl compounds, particularly compounds of formula I, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat cognitive impairment associated with Parkinson's disease or schizophrenia.
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3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL)PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS (Thu, 27 Oct 2016)
A compound of formula (I) or a salt thereof are provided wherein R<sp>1</sp>, X and R<sp>3</sp> are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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QUINOLONE COMPOUND AND PHARMACEUTICAL COMPOSITION (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a quinolone compound represented by General Formula (1)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="55.54mm" file="US20160304461A1-20161020-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt thereof, wherein R<sub>1 </sub>represents a hydrogen atom, etc.; R<sub>2 </sub>represents a hydrogen atom, etc.; R<sub>3 </sub>represents a phenyl group optionally being substituted with one or more substituents, etc.; R<sub>4 </sub>represents a halogen atom; R<sub>5 </sub>represents a hydrogen atom or halogen atom; R<sub>6 </sub>represents a hydrogen atom; and R<sub>7 </sub>represents a hydroxyl group, etc. The quinolone compound have a functional improvement effect, which suppresses progression of neurological dysfunction by inhibiting the chronic progression of Parkinson's disease or protecting dopamine neurons from the disease etiology, thereby prolonging the period before first administration begins.</p>
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NOVEL COMPOUNDS AS JNK KINASE INHIBITORS (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to modulators, such as inhibitors, of JNK isoform 2 (JNK2) or isoform 3 (JNK3) comprising compounds of formula (I) or formula (II) as described herein. Compounds of the invention can be used for treatment of a medical disorder in a patient wherein modulation of JNK3 is medically indicated, such as when the disorder is Parkinson disease (PD) Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), myocardial infarction (MI), glaucoma, obesity, diabetes, cancer, rheumatoid arthritis, fibrotic disease, pulmonary fibrosis, kidney disease, liver inflammation, Crohns disease, hearing loss, Prader Willi syndrome, or a condition where modification of feeding behavior is medically indicated.</p>
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Compositions and methods for treating neurodegenerative diseases (Fri, 21 Oct 2016)
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 Huntingtons Disease, Parkinson's Disease, and Alzheimers Disease.
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Heteroaromatic compounds and their use as dopamine D1 ligands (Fri, 21 Oct 2016)
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 D1-mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 07 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to substituted indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.</p>
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GUANIDINOGLYCOSIDE-MEDIATED LIPOSOME-BASED DELIVERY OF THERAPEUTICS (Fri, 07 Oct 2016)
This disclosure relates to the incorporation of amphiphilic guanidinylated aminoglycosides (e.g., neomycin) into liposomal assemblies, which contain entrapped therapeutics. The lysosome is responsible for enzymatically breaking down and recycling large biomolecules and aged organelles. While malfunctioned lysosomal enzymes have been established in Lysosomal Storage Disorders (LSDs), recent reports have suggested that defects in lysosomal enzymes (e.g., glucocerebrosidase) are also linked to other chronic ailments, including neurological disorders such as Parkinson's Disease and related disorders.
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Pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds as CDK inhibitors and their therapeutic use (Fri, 07 Oct 2016)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, <i>inter alia</i>, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Thu, 06 Oct 2016)
Compounds of the formula I or pharmaceutically acceptable salts thereof, wherein m, n. X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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PYRAZOLYL PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 30 Sep 2016)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Heteroaromatic compounds and their use as dopamine D1 ligands (Fri, 30 Sep 2016)
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 D1-mediated (or D1 -associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">A compound of Formula I is provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.01mm" wi="56.98mm" file="US20160272628A1-20160922-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula I.</p>
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also 10 relates to a process for manufacturing compounds of Formula I.
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TRIAZOLYL PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 23 Sep 2016)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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TRIAZOLYL PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS (Fri, 23 Sep 2016)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Triazolyl pyrimidinone compounds as PDE2 inhibitors (Fri, 23 Sep 2016)
The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also 10 relates to a process for manufacturing compounds of Formula I.
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NOVEL 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">4-(Indol-3-yl)-pyrazole derivative compounds of Formula I or pharmaceutically acceptable enantiomers, salts or solvates thereof are provided. Further provided is the use of the compounds of Formula I as TDO2 inhibitors. Also provided herein is use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity.</p>
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METHODS FOR TREATING PROTEINOPATHIES (Fri, 16 Sep 2016)
This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.
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Methods for treating proteinopathies (Fri, 16 Sep 2016)
This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.
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THERAPEUTIC COMPOUNDS (Sat, 10 Sep 2016)
The invention provides compounds formula (I) and salts thereof: wherein R1-R4 have any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, inflammation, hyperresponsiveness, allergic conditions, asthma, and psychotic disorders such as schizophrenia. The compounds are also useful to lower IL-4, IL-5, or IL-15 levels in an animal.
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A PROCESS FOR THE PREPARATION OF A CAMSYLATE SALT ((1S)-(+)-10 CAMPHORSULFONIC ACID) OF (1R,1'R,4R)- 4-METHOXY-5"-METHYL-6'-[5-(PROP-1-YN-1-YL)PYRIDIN- 3-YL]-3'H-DISPIRO[CYCLOHEXANE-1,2'-INDEN-1'2'-IMIDAZOLE]-4"-AMINE (Thu, 08 Sep 2016)
A process for the preparation of a camsylate salt ((1S)-(+)-10 camphorsulfonic acid) of (1r,1'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin- 3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine is disclosed as well as pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating A²-related pathologies such as Alzheimer's Disease, Down's Syndrome, ²-amyloid angiopathy and conditions such as dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's Disease, progressive supranuclear palsy or cortical basal degeneration.
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Uridine diphosphate derivatives, prodrugs, compositions and methods for treating neurodegenerative disorders (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">This disclosure relates to prodrugs of uridine diphosphate (UDP) derivatives, compositions comprising therapeutically effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma, and inflammatory conditions.</p>
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LRRK2 INHIBITORS AND METHODS OF MAKING AND USING THE SAME (Fri, 19 Aug 2016)
Compounds having the formula (I), (II), (III) are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.
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Heteroaryl amides as inhibitors of protein aggregation (Fri, 12 Aug 2016)
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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Compositions and methods using the same for treatment of neurodegenerative and mitochondrial disease (Fri, 12 Aug 2016)
The present disclosure is directed, in part, to compounds, or pharmaceutically acceptable salts thereof, for the treatment and/or prevention of neurodegenerative disease and/or mitchonodrial disease including Parkinson's disease and Leigh's disease.
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COMT Inhibiting Methods and Compositions (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.18mm" wi="51.22mm" file="US20160222001A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMT Inhibiting Methods and Compositions (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="51.22mm" file="US20160222011A1-20160804-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMT INHIBITING METHODS AND COMPOSITIONS (Fri, 05 Aug 2016)
The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.
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COMT INHIBITING METHODS AND COMPOSITIONS (Fri, 05 Aug 2016)
The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula (I), or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.
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Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment (Fri, 05 Aug 2016)
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 a5- containing GABA<sb>A</sb> receptor agonist (<i>e.g.</i>, a α5 -containing GABA<sb>A</sb> 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.
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Anti-depression compounds (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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Neuroprotective polyphenol analogs (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzheimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.</p>
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Heteroaryl amides as inhibitors of protein aggregation (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.</p>
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Compound or mixture of compounds for the treatment of neurodegenerative diseases or oxidative stress injuries (Thu, 21 Jul 2016)
A composition for the treatment and prevention of neurodegenerative disease and injuries induced by oxidative stress comprising coptisine or an extract from Coptis rhizome including pharmaceutically acceptable salts, tautomers and stereoisomers of the compound, including mixtures thereof in all ratios, is provided. Preferably the coptisine is combined with at least one further compound selected from the group including berberine, jatrorrhizine and palmitine including pharmaceutically acceptable salts, tautomers and stereoisomers of the compounds, including mixtures thereof in all ratios. The neurodegenerative disease may be selected from the group including Alzheimers disease and other dementias, brain cancer, degenerative nerve disease, encephaltitis, epilepsy, genetic brain disorders, head and brain malformations, hydrocephalus, stroke, Parkinsons disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease) Huntingtons disease and prion diseases. Coptisine or an extract from Coptis rhizome for modulating the activity of thioredoxine-interacting protein is also provided.
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 15 Jul 2016)
<p id="p-0001" num="0000">The present invention is directed to azaindazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.</p>
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PRODUCTION METHOD OF THIAZOLE DERIVATIVE (Fri, 15 Jul 2016)
Provided is a production method of a thiazole derivative represented by the formula (I), which has an adenosine A2A receptor antagonistic action and is useful as a therapeutic agent for, for example, Parkinson's disease, sleep disorder, analgesic resistance to opioid, migraine, movement disorder, depression, anxiety disorder and the like. Also provided is a production method of a compound represented by the formula (C), which contains (i) a step of reacting a compound represented by the formula (A) and a compound represented by the formula (B), and the like: (wherein R1 represents furyl, R4, R5 and R6 are the same or different and each represents lower alkyl or aryl, R2 represents pyridyl or tetrahydropyranyl, and X1 represents halogen).
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Production method of thiazole derivative (Fri, 15 Jul 2016)
Provided is a production method of a thiazole derivative represented by the formula (I), which has an adenosine A<sb>2A</sb> receptor antagonistic action and is useful as a therapeutic agent for, for example, Parkinson's disease, sleep disorder, analgesic resistance to opioid, migraine, movement disorder, depression, anxiety disorder and the like. Also provided is a production method of a compound represented by the formula (C), which contains (i) a step of reacting a compound represented by the formula (A) and a compound represented by the formula (B), and the like: (wherein R<sp>1</sp> represents furyl, R<sp>4</sp>, R<sp>5</sp> and R<sp>6</sp> are the same or different and each represents lower alkyl or aryl, R<sp>2</sp> represents pyridyl or tetrahydropyranyl, and X<sp>1</sp> represents halogen).
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Compounds (Fri, 08 Jul 2016)
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 characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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Compounds (Fri, 08 Jul 2016)
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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Bismuth-containing compounds, coordination polymers, methods for modulating pharmacokinetic properties of biologically active agents, and methods for treating patients (Fri, 08 Jul 2016)
Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient. 7R7040P 1 (CHMattr) P103435 Al J RONIAM 1 o19 bicadhesive 5-ASA adjuvant bl aodajduhvaenstive 5-ASA
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TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND METHODS OF PREPARATION AND USES THEREOF (Fri, 08 Jul 2016)
Disclosed are a trifluoroacethydrazide compound as well as preparation and application thereof. The compound has a structure represented by general formula (I). The compound has multiple mechanisms of action, comprising inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, and the effect of scavenging free radicals and promoting neural differentiation, and thus has a desirable protective effect on neurocytes and can alleviate memory impairment of a scopolamine-induced mouse model. The compound can be used for preparing a medicament having a cell protective effect, which is used for preventing or treating diseases related to glutamate excitotoxicity, MEF2 imbalance or overproduction of free radicals, e.g., diseases related to neurodegeneration comprising senile dementia, Parkinson's disease, cerebral stroke and the like, and diseases related to free radicals 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, 01 Jul 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.</p>
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Aminopyridine Derived Compounds as LRRK2 Inhibitors (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">The present invention is directed to aminopyridine derived compounds of formula (A)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="69.85mm" file="US20160184317A1-20160630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds are considered useful for the treatment of diseases associated with LRRK2 such a Lewy body dementia, Parkinson's disease or cancer.</p>
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BIDENTATE-BINDING MODULATORS OF LRRK2 AND JNK KINASES (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Both JNK and LRRK2 are associated with Parkinson's disease (PD), myocardial infarction (MI), and other medical disorders. Here we report a reasonably selective and potent kinase inhibitors (e.g., compounds 6 and 10) that bound to both JNK and LRRK2 (a dual inhibitor). A bidentate-binding strategy that simultaneously utilized the ATP hinge binding and a unique protein surface site outside of the ATP pocket was applied to the design and identification of this kind of inhibitor. Compound 6 was a potent JNK3 and modest LRRK2 dual inhibitor with an enzyme IC50 value of 12 nM and 99 nM (LRRK2-G2019S), respectively. 6 also exhibited good cell potency, inhibited LRRK2:G2019S induced mitochondrial dysfunction in SHSY5Y cells, and was demonstrated to be reasonably selective against a panel of 116 kinases from representative kinase families.</p>
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Gastric retentive dosage forms for extended release of acamprosate into the upper gastrointestinal tract (Fri, 01 Jul 2016)
<p id="p-0001" num="0000">Gastric retentive dosage forms for sustained release of acamprosate are described which may allow once- or twice-daily dosing for both acute and long-term treatment of a disorder including alcohol dependence, tinnitus, sleep apnea, Parkinson's disease, levodopa-induced dyskinesias in Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, Cortical spreading depression, migraine, schizophrenia, anxiety, tardive dyskinesia, spasticity, multiple sclerosis, various types pain, or binge eating. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.</p>
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CRYSTAL FORMS OF APOMORPHINE AND USES THEREOF (Fri, 01 Jul 2016)
The present invention provides solid crystalline forms of apomorphine free base or a hydrate, solvate, or co-crystals thereof. Such crystalline forms may be advantageous over amorphous forms of apomorphine, e.g., amorphous salt forms such as acid addition salts of apomorphine, because of their increased/greater stability and/or improved pharmacological properties, e.g., decreased adverse reactions at the site of administration. The invention further provides liquid formulations obtained by dissolving said crystalline forms of apomorphine in a solvent, as well as a method for treatment of a neurological or movement disorder, e.g., Parkinson's disease, or a condition associated therewith, by administration of said liquid formulations.
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COMPOUNDS FOR USE AS PAIN THERAPEUTICS (Fri, 01 Jul 2016)
This disclosure provides compounds and compositions for use as analgesics and for the treatment of one or more conditions selected from: pain; psychic pain; psychological pain; psychiatric pain; depression; allodynia; fibromyalgia; fibromyalgia-ness; central sensitization; centralization; regional pain syndrome; temporomandibular joint syndrome (TMJ); lower back pain; interstitial cystitis; Gulf War syndrome; visceral pain; phantom limb painj.kidney stones; gout; neuropathic pain; post-herpetic neuralgia; diabetic neuropathy; sickle cell pain; priapism; nociceptive pain; post-operative pain; orthopedic injury pain; bunionectomy; dental extraction; pain after severed spinal cord injury; osteoarthritis; rheumatoid arthritis; Lyme disease; Parkinson's disease; opioid-induced constipation; an opioid withdrawal symptom; pain associated with post-traumatic stress disorder (PTSD); and combinations of any of the foregoing conditions. This disclosure also provides compounds that are ligands, and in some embodiments, modulators (e.g., agonists), for the imidazoline receptor type 1.
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Magnesium compositions and uses thereof for neurological disorders (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">A composition for administration to a subject, such as oral administration to a subject, for example, has been provided. Such a composition may comprise at least one magnesium-counter ion compound. A magnesium-counter ion composition described herein may be useful for any of a variety of applications provided herein, such as maintaining, enhancing, and/or improving health, nutrition, and/or another condition of a subject, and/or cognitive, learning, and/or memory function. A magnesium-counter ion composition provided herein may be useful for administration to a subject presenting magnesium deficiency, mild cognitive impairment, Alzheimer's disease, attention deficit hyperactivity disorder, ALS, Parkinson's disease, diabetes, migraine, anxiety disorder, mood disorder, and/or hypertension. A kit, method, and other associated technology are also provided.</p>
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HETEROCYCLIC DERIVATIVES MODULATING ACTIVITY OF CERTAIN PROTEIN KINASES (Fri, 24 Jun 2016)
The present invention relates to novel heterocyclic derivatives having general formula (I) and their therapeutic use for diseases such as cancer, inflammation, pain, autoimmune diseases or neurodegenerative diseases like Alzheimer's or Parkinson's disease that can be treated by modulation of certain protein kinases. Compounds of formula (I) can be used for treatment of patients who do not respond to kinase inhibition therapy that comprises currently available medications.
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2,3,4,5-TETRAHYDROPYRIDIN-6-AMINE AND 3,4-DIHYDRO-2H-PYRROL-5-AMINE COMPOUND INHIBITORS OF BETA-SECRETASE (Fri, 24 Jun 2016)
The present invention relates to 2,3,4,5-tetrahydropyridin-6-amine and 3,4- dihydro-2H-pyrrol-5-amine compound inhibitors of beta-secretase having the structure shown in Formula (I), wherein the radicals are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia associated with beta- amyloid, age-related macular degeneration, type 2 diabetes or metabolic disorders.
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3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOIC ACID USEFUL AS KYNURENINE MONOOXYGENASE INHIBITORS (Fri, 24 Jun 2016)
Compound of formula (I) wherein R1 is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl; and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disewase, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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3-(6-alkoxy-5-chlorobenzo[d]isoxazol-3-yl)propanoic acid useful as kynurenine monooxygenase inhibitors (Fri, 24 Jun 2016)
Compound of formula (I) wherein R<sp>1</sp> is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R<sp>2</sp> is H, methyl or ethyl; and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disewase, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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Novel compositions for preventing and/or treating degenerative disorders of the central nervous system (Fri, 24 Jun 2016)
[00130] The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.
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INHIBITORS OF HUMAN 12/15-LIPOXYGENASE (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.</p>
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KINETICS BIOMARKERS FOR NEURODEGENERATION (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to novel diagnostic, prognostic, predictive and pharmacodynamic properties with regard to amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD) with and without dementia components. The methods described herein will prove very useful in the development of diagnostic as well as treatment strategies for patients with amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD).</p>
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Compounds for treatment of alzheimer's disease (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The invention is directed to the use of a compound of formula I, as defined herein, to a pharmaceutically acceptable salt thereof; to a pharmaceutical composition containing a compound of formula I, and to a combination of a compound of formula I with a pharmacologically effective cholinesterase inhibitor to treat a mammal, including a human, for a disorder or condition selected from the list including Alzheimer's disease, Huntington's disease, Parkinson's disease, non-Alzheimer's dementias and ALS.</p>
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GLYCINE TRANSPORTER INHIBITOR (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds of formula [I] or pharmaceutically acceptable salts thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.25mm" wi="76.28mm" file="US20160159814A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.</p>
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Pyrroloquinoline derivatives as 5-HT<sub>6 </sub>antagonists, preparation method and use thereof (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">This invention concerns pyrroloquinoline derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome. The compounds have the general formula (XIV), wherein the symbols have the meanings given in the description.</p>
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Thu, 09 Jun 2016)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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PPAR-sparing compounds for the treatment of metabolic diseases (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to hydroxamate compounds and pharmaceutical compositions that are useful for treating and/or preventing metabolic inflammation mediated diseases such as diabetes, obesity, hypertension, dyslipidemia, a neurodegenerative disorder (e.g., Alzheimer's disease, Parkinson's disease, or Huntington's disease), or any combination thereof. Moreover, the present invention also provides methods of treatment for these diseases or disorders.</p>
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GLYCOLIPIDS AS TREATMENT FOR DISEASE (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">This invention provides compounds, compositions, and methods for treating a disorder selected from cancer, hyperinsulinemia, hypoglycemia, hyperinsulinemia with hypoglycemia, atypical Parkinson's disease, Huntington's disease, multiple systems atrophy, GM3 synthase deficiency, GM2 synthase deficiency or tauopathy.</p>
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5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid.</p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.66mm" wi="53.68mm" file="US09518042-20161213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="69.85mm" file="US09499516-20161122-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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Substituted benzamide derivatives as in vitro MAO-B inhibitors (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The invention relates to the use of substituted benzamide derivatives of Formula I: Wherein: A<sup>1 </sup>and A<sup>2 </sup>are —N or —CH, so that if A<sup>1 </sup>is —N, then A<sup>2 </sup>is —CH and If A<sup>2 </sup>is —N, then A<sup>1 </sup>is —CH; R is a hydrogen atom, or represents branched or unbranched —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), —(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen, or R is a group wherein R<sup>3 </sup>and R<sup>4 </sup>both together or independently are halogen, hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, —O—(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), —O—(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen; R<sup>1 </sup>and R<sup>2 </sup>both together or independently are halogen, hydroxyl, —(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —(C<sub>1</sub>-C<sub>3</sub>C)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, —O—(C<sub>1</sub>-C<sub>3</sub>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, —O—(C<sub>1</sub>-C<sub>3</sub>)—O—(C<sub>1</sub>-C<sub>3</sub>), -0-(C<sub>1</sub>C<sub>3</sub>)—O—(C<sub>1</sub>C<sub>3</sub>), wherein one, two or three hydrogen atoms may be substituted by a halogen, their pharmaceutically acceptable salts, isomers or mixtures thereof as in vitro selective MAO-B inhibitors. The substituted benzamide derivatives of Formula I, their pharmaceutically acceptable salts, isomers or mixtures thereof are useful for the manufacture of a medicament for prevention and treatment of acute and chronic neurological disorders, cognitive and neurodegenerative diseases, more precisely for the manufacture of a medicament for prevention and treatment of neurodegenerative disorders such as Parkinson's Disease and Alzheimer's Disease.</p>
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GLYCINE TRANSPORTER INHIBITOR (Thu, 02 Jun 2016)
The present invention provides novel compounds of formula [I] or pharmaceutically acceptable salts thereof: which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.
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AMINOPYRAZINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES (Fri, 27 May 2016)
Disclosed are compounds of Formula A and Formula A-1, or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof; wherein "R1", "RA-1", "R2", "R3", and "Het" are defined herein above, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
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Aminopyrazine compounds with A2A antagonist properties (Fri, 27 May 2016)
Disclosed are compounds of Formula A and Formula A-1, or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof; wherein "R<sp>1</sp>", "R<sp>A-1</sp>", "R<sp>2</sp>", "R<sp>3</sp>", and "Het" are defined herein above, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
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BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 20 May 2016)
<p id="p-0001" num="0000">Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M<sub>1</sub>, M<sub>2</sub>, M<sub>3</sub>, M<sub>4</sub>, M<sub>5</sub>) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. Additional bitopic muscarinic antagonists discovered and described herein include BK-23, HD-42, HD153, HD-185, KH-5, JM-31 and JM-32. These bitopic ligands and their structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M<sub>1</sub>-M<sub>5 </sub>acetylcholine receptors.</p>
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COMPOUNDS FOR USE AS IMAGING AGENTS (Fri, 20 May 2016)
The present invention describes the use of the Chinese medicinal compounds ginsenoside RB1, dihydromyricetin and salvianohc acid B, for use in diagnosing, monitoring and treating synucleinopathies, such as Parkinson's disease, in patients.
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SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF AND METHODS FOR THE PRODUCTION AND USE THEREOF (Thu, 19 May 2016)
The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT 6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT 6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity. In the general formula 1: wherein: X = S, SO or NH; R 1 represents hydrogen, optionally substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R 2 represents hydrogen, halogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R 3 represents hydrogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X = S or X = NH, at least one of R 1 , R 2 or R 3 represent substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R 1 , R 2 or R 3 represent hydrogen; R 4 represents C 1 -C 3 alkyl; R 5 represents hydrogen, one or two halogens, C 1 -C 3 alkyl or optionally substituted hydroxyl.
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4-amino-6-phenyl-6,7-dihydro[1,2,3]triazolo[1,5-A]pyrazine derivatives as inhibitors of beta-secretase (BACE) (Fri, 13 May 2016)
<p id="p-0001" num="0000">The present invention relates to novel 6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6-yl derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.</p>
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Map kinase modulators and uses thereof (Fri, 13 May 2016)
<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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SUBSTITUTED PYRAZOLO(1,5-A)PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 May 2016)
The invention provides substituted pyrazolo[l,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[l,5-a]pyrimidine compounds described herein include 5,7- dimethyl-N-phenylpyrazolo[l,5-a]pyrimidine-3-carboxamide compounds and variants thereof.
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SUBSTITUTED IMIDAZO[1,5-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 May 2016)
The invention provides substituted imidazo[1,5-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidine compounds described herein include substituted 2,4-dimethyl-N-phenylimidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.
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SUBSTITUTED PYRROLO[1,2-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS (Fri, 13 May 2016)
The invention provides substituted pyrrolo[l,2-a]pyrimi dines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-N-phenylpyrrolo[l,2-a]pyrimidine-8-carboxamide compounds and variants thereof.
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Compositions and methods for prevention and treatment of brain diseases and conditions (Fri, 13 May 2016)
Disclosed herein are compounds, extracts, and active fractions of the plant Geum japonicum and methods for preventing or treating brain diseases or conditions, such as ischemic stroke, Alzheimer's disease, vascular dementia, mild cognitive impairment (MCI), chronic cerebral ischemia and Parkinson's disease. The compounds provided herein can be formulated into pharmaceutical compositions and medicaments that are useful in the disclosed methods. Also provided are the use of the compounds and extracts in preparing pharmaceutical formulations and medicaments.
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Substituted pyrazolo(1,5-a)pyrimidines and their use in the treatment of medical disorders (Fri, 13 May 2016)
The invention provides substituted pyrazolo[l,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[l,5-a]pyrimidine compounds described herein include 5,7- dimethyl-<i>N</i>-phenylpyrazolo[l,5-a]pyrimidine-3-carboxamide compounds and variants thereof.
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Substituted pyrrolo(1,2-a)pyrimidines and their use in the treatment of medical disorders (Fri, 13 May 2016)
The invention provides substituted pyrrolo[l,2-a]pyrimi dines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-<i>N</i>-phenylpyrrolo[l,2-a]pyrimidine-8-carboxamide compounds and variants thereof.
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GHRELIN SPLICE VARIANT FOR TREATING NEURONAL DAMAGE,NEURODEGENERATIVE DISEASE, PARKINSONS DISEASE, ALZHEIMERS DISEASE, AND/OR DEPRESSION (Fri, 06 May 2016)
<p id="p-0001" num="0000">The present disclosure relates, in one aspect, to use of ghrelin splice variant or an analogue thereof, or a ghrelin splice variant-like compound for the preparation of a medicament for one or more of: treatment and/or prevention of neuronal damage and/or neurodegeneration and, prophylaxis or treatment of neuronal damage and/or neurodegenerative disease, Parkinson's disease, Alzheimer's disease, depression stimulation of neuronal activity. A further aspect relates to a number of new ghrelin splice variant-like compounds and uses thereof, as well as to pharmaceutical compositions and medical packaging comprising the new ghrelin splice variant-like compounds.</p>
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CONJUGATES OF POLYUNSATURATED FATTY ACIDS AND AMINE-CONTAINING COMPOUNDS AND USES THEREOF (Fri, 06 May 2016)
<p id="p-0001" num="0000">Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases, dermatitis and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis.</p>
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4-amino-6-phenyl-5,6-dihydroimidazo[1,5-A]pyrazine derivatives as inhibitors of beta-secretase (BACE) (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazinyl derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.</p>
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4-AMINO-6-PHENYL-5,6-DIHYDROIMIDAZO[1,5-A]PYRAZIN-3(2H)-ONE DERIVATIVES AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 29 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazin-3(2H)-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.</p>
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DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF (Fri, 29 Apr 2016)
Provided herein are compounds of formula (I) and compositions containing the compounds. The compounds and compositions are useful in the methods of treating, amelioration or prophylaxix of diseases associated with Nrf2/ NF-κΒ pathways. The diseases associated include, but are not limited to a fibrotic disease such as lung fibrosis, liver fibrosis, kidney fibrosis, and scleroderma, or a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, and sickle cell disease.
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CARBIDOPA AND L-DOPA PRODRUGS AND THEIR USE TO TREAT PARKINSON'S DISEASE (Fri, 29 Apr 2016)
The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.
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Carbidopa and L-dopa prodrugs and their use to treat Parkinson's disease (Fri, 29 Apr 2016)
The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.
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INDOLIN-2-ONE OR PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE DERIVATIVES (Thu, 28 Apr 2016)
The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula (I) wherein Ar is a heteroaryl group, containing one, two or three heteroatoms, selected from N, S or O; R<sp>1</sp> is hydrogen, lower alkyl, halogen, amino, dimethylamino, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, CH(OH)CF<sb>3</sb>, (CH<sb>2</sb>)<sb>o</sb>-lower alkoxy, cycloalkyl optionally substituted by CF<sb>3</sb>, or heterocycloalkyl optionally substituted by lower alkyl; R<sp>2</sp> is hydrogen, lower alkyl, (CH<sb>2</sb>)<sb>o</sb>-cycloalkyl, (CH<sb>2</sb>)<sb>o</sb>-O-cycloalkyl, (CH<sb>2</sb>)<sb>o</sb>-lower alkoxy, CH<sb>2</sb>)<sb>o</sb>-lower alkoxy substituted by halogen, (CH<sb>2</sb>)<sb>o</sb>-heterocycloalkyl optionally substituted by lower alkyl, (CH<sb>2</sb>)<sb>o</sb>-S(O)<sb>2</sb>-cycloalkyl, lower alkyl substituted by one or two hydroxy, lower alkyl substituted by one or two lower alkoxy, (CH<sb>2</sb>)<sb>o</sb>-S(O)<sb>2</sb>-lower alkyl, lower alkyl substituted by halogen or CH<sb>2</sb>CH(OH)CF<sb>3</sb>; R<sp>3</sp> is halogen or lower alkyl; X is CH or N; X<sp>1</sp> is CH or N; n is 1 or 2; o is 0, 1, 2 or 3; m is 0, 1 or 2; and the dotted line is a bond or not; as well as with a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof The compounds may be used for the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.
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4-(5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)-1,4-dimethyl-1H-pyrrol-3-yl)benzenesulfonamide as alpha 7 nAChR modulator (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">Disclosed are an alpha 7 nAChR receptor modulator compound, 4-(5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)-1,4-dimethyl-1H-pyrrol-3-yljbenzenesulfonamide, its tautomeric form, its pharmaceutically acceptable salts, pharmaceutical compositions comprising the compound or a salt thereof, and a method of treating various diseases, disorders or conditions, for example, Alzheimer's disease, mild cognitive impairment, senile dementia, vascular dementia, dementia of Parkinson's disease, and attention deficit disorder.</p>
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Carbidopa and L-dopa prodrugs and methods of use (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.</p>
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FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE (Fri, 22 Apr 2016)
Monomethyl and monoethyl fumarate prodrugs, pharmaceutical compositions comprising the monomethyl and monoethyl fumarate prodrugs, and methods of using monomethyl and monoethyl fumarate prodrugs and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed.
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GLYCINE TRANSPORTER INHIBITOR (Thu, 21 Apr 2016)
The present invention provides novel compounds of formula [IA] or pharmaceutically acceptable salts thereof: which are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.
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PROGRANULIN FOR USE IN TREATING PARKINSON'S DISEASE OR ALZHEIMER'S DISEASE (Thu, 21 Apr 2016)
The invention relates to methods and compositions for treating a neurodegenerative disease. More particularly, the present invention is directed to methods of treatment of neurodegenerative diseases using progranulin and progranulin polypeptides, and methods of treatment of neurodegenerative diseases using effectors, or combinations of effectors, that modify progranulin expression.
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4-AMINO-6-PHENYL-5,6-DIHYDROIMIDAZO[1,5-A]PYRAZIN-3(2H)-ONE DERIVATIVES AS INHIBITORS OF BETA-SECRETASE (BACE) (Thu, 21 Apr 2016)
The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazin-3(2<i>H</i>)-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.
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Arylpyrrolopyridine derived compounds as LRRK2 inhibitors (Fri, 15 Apr 2016)
<p id="p-0001" num="0000">The present invention is directed to arylpyrrolopyridine derivatives of formula (A) (A). The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Lewy body dementia, Parkinson's disease cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="54.36mm" file="US09499542-20161122-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 15 Apr 2016)
The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
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3,4-DIHYDROISOQUINOLIN-2(1H)-YL COMPOUNDS (Thu, 14 Apr 2016)
The invention provides certain 3,4-dihydroisoquinolin-2(1H)-yl compounds, particularly compounds of formula (I), and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula (I) to treat cognitive impairment associated with Parkinson's disease or schizophrenia.
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STEROIDAL NITRONES FOR THE TREATMENT AND PREVENTION OF A CEREBRAL STROKE OR ISCHAEMIA, ALZHEIMER AND PARKINSON DISEASE AND AMYOTROPHIC LATERAL SCLEROSIS (Fri, 01 Apr 2016)
<p id="p-0001" num="0000">The invention relates to neuroprotective, antioxidant steroidal nitrones to which the blood-brain barrier is highly permeable, as potential drugs for the treatment of a cerebral stroke or ischaemia, Alzheimer and Parkinson disease and amyotrophic lateral sclerosis.</p>
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COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF BETA-AMYLOID DISEASES AND SYNUCLEINOPATHIES (Fri, 01 Apr 2016)
Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of -amyloid diseases, such as observed in Alzheimer's disease, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.
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STEROIDAL NITRONES FOR THE TREATMENT AND PREVENTION OF A CEREBRAL STROKE OR ISCHAEMIA, ALZHEIMER AND PARKINSON DISEASE AND AMYOTROPHIC LATERAL SCLEROSIS (Thu, 31 Mar 2016)
The invention relates to neuroprotective, antioxidant steroidal nitrones to which the blood-brain barrier is highly permeable, as potential drugs for the treatment of a cerebral stroke or ischaemia, Alzheimer's and Parkinson's disease and amyotrophic lateral sclerosis.
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KINETICS BIOMARKERS FOR NEURODEGENERATION (Fri, 25 Mar 2016)
The present invention relates to novel diagnostic, prognostic, predictive and pharmacodynamic properties with regard to amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD) with and without dementia components. The methods described herein will prove very useful in the development of diagnostic as well as treatment strategies for patients with amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD).
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MACROCYCLIC LRRK2 KINASE INHIBITORS (Fri, 25 Mar 2016)
The present invention relates to novel macrocyclic compounds of formula (I) and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 (Leucine-Rich Repeat Kinase 2). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine or diagnostic agent, in particular for the treatment and/or diagnosis of diseases characterized by LRRK2 kinase activity such as neurological disorders including Parkinson's disease and Alzheimer's disease.
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Naphthyl sulfonamide derivatives as KEAP-1 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders (Thu, 24 Mar 2016)
The present invention relates to naphthyl sulfonamide derivatives of the formula I in which R1, R2, R3, R4, R5, R6, R10, A, D, X, q, i, n, L and R50 are defined as indicated below. The naphthyl sulfonamide derivatives I are KEAP-1 modulators and useful for the prevention and/or treatment of diabetes, obesity, dyslipidemia and related disorders, neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. The invention furthermore relates to the use of naphthyl sulfonamide derivatives of the formula I or II as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.
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4-(p-quinonyl)-2-hydroxybutanamide derivatives for treatment of mitochondrial diseases (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.</p>
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Pro-neurogenic compounds (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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URIDINE NUCLEOSIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">This disclosure relates to uridine nucleoside derivatives, compositions comprising therapeutically effective amounts of those nucleoside derivatives and methods of using those nucleoside derivatives or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma and inflammatory conditions.</p>
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3, 4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.</p>
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AMINOMETHYL- AND METHYLOXY-LINKED TRICYCLIC COMPOUNDS AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 18 Mar 2016)
The present invention relates to certain aminomethyl- and methyloxy-linked tricyclic compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy.
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COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Fri, 11 Mar 2016)
The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R9, and A are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.
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Pyrroloquinoline derivatives as 5-HT6 antagonists, preparation method and use thereof (Fri, 11 Mar 2016)
This invention concerns pyrroloquinoline derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in schizophrenia, anxiety, depression, maniac depression, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, panic attacks, attention deficit hyperactivity disorder, attention deficit disorder, Parkinson's disease, Huntington's disease, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, obesity and type-2 diabetes, functional bowel disorder, Irritable Bowel Syndrome. The compounds have the general formula (XIV), wherein the symbols have the meanings given in the description.
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SUBSTITUTED BENZAMIDE DERIVATIVES AS MAO-B INHIBITORS (Thu, 10 Mar 2016)
The invention relates to the use of substituted benzamide derivatives of Formula I: Wherein: A<sp>1</sp> and A<sp>2</sp> are -N or -CH, so that if A<sp>1</sp> is -N, then A<sp>2</sp> is -CH and If A<sp>2</sp> is -N, then A<sp>1</sp> is -CH; R is a hydrogen atom, or represents branched or unbranched -(C<sb>1</sb>-C<sb>3</sb>)-alkyl, -(C<sb>1</sb>-C<sb>3</sb>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, -(C<sb>1</sb> -C<sb>3</sb>)-O-(C<sb>1</sb>-C<sb>3</sb>), -(C<sb>1</sb>-C<sb>3</sb>)-O-(C<sb>1</sb>-C<sb>3</sb>), wherein one, two or three hydrogen atoms may be substituted by a halogen, or R is a group wherein R<sp>3</sp> and R<sp>4 </sp>both together or independently are halogen, hydroxyl, -(C<sb>1</sb>-C<sb>3</sb>)alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, -O-(C<sb>1</sb>-C<sb>3</sb>)-alkyl, -O-(C<sb>1</sb>-C<sb>3</sb>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, -O-(C<sb>1</sb>-C<sb>3</sb>)-O-(C<sb>1</sb>-C<sb>3</sb>), -O-(C<sb>1</sb>-C<sb>3</sb>)-O-(C<sb>1</sb>-C<sb>3</sb>), wherein one, two or three hydrogen atoms may be substituted by a halogen; R<sp>1</sp> and R<sp>2</sp> both together or independently are halogen, hydroxyl, -(C<sb>1</sb>-C<sb>3</sb>)-alkyl, -(C<sb>1</sb>-C<sb>3</sb>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen or hydroxyl, -O- (C<sb>1</sb>-C<sb>3</sb>)-alkyl, -O-(C<sb>1</sb>-C<sb>3</sb>)-alkyl, wherein one, two or three hydrogen atoms may be substituted by a halogen, -Ο-(C<sb>1</sb>-C<sb>3</sb>)-Ο-(C<sb>1</sb>-C<sb>3</sb>), -0-(C<sb>1</sb>C<sb>3</sb>)-O-(C<sb>1</sb>C<sb>3</sb>), wherein one, two or three hydrogen atoms may be substituted by a halogen, their pharmaceutically acceptable salts, isomers or mixtures thereof as in vitro selective MAO-B inhibitors. The substituted benzamide derivatives of Formula I, their pharmaceutically acceptable salts, isomers or mixtures thereof are useful for the manufacture of a medicament for prevention and treatment of acute and chronic neurological disorders, cognitive and neurodegenerative diseases, more precisely for the manufacture of a medicament for prevention and treatment of neurodegenerative disorders such as Parkinson's Disease and Alzheimer's Disease.
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.</p>
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Substituted benzimidazoles as nociceptin receptor modulators (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">The invention provides modulators of the nociceptin receptor (NOP), including both agonists and antagonists. A compound of the invention can be a selective modulator of NOP with respect to the μ- and κ-opioid receptors (MOP and KOP), thus providing a therapeutic method for the treatment of conditions wherein selective NOP modulation is medically indicated and MOP or KOP modulation may be less desirable. A compound of the invention can be a NOP full agonist, partial agonist, inverse agonist, positive or negative allosteric modulator, or a functionally biased agonist. A compound of the invention can be used for the treatment of an anxiety state, post-traumatic stress disorder, addictive disorders (including overuse of alcohol, tobacco, and drugs of abuse such as cocaine, amphetamines, and opitates), misregulated food intake and/or energy expenditure, cough, sleep disorders, migraine, pain, depression, or neurodegenerative disorders such as Parkinsons disease or Alzheimers disease.</p>
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ARYLPYRROLOPYRIDINE DERIVED COMPOUNDS AS LRRK2 INHIBITORS (Thu, 25 Feb 2016)
The present invention is directed to arylpyrrolopyridine derivatives of formula (A) (A). The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Lewy body dementia, Parkinson's disease cancer.
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HETEROCYCLIC ACETIC ACID AMIDE COMPOUND (Thu, 25 Feb 2016)
[Problem] A compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM) is provided. [Means for Solution] The present inventors have studied a compound which has a dopamine D1 receptor positive allosteric modulating activity and is useful as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like, and they have thus found that a heterocyclic acetamide compound has a dopamine D1 receptor positive allosteric modulating activity, thereby completing the present invention. The heterocyclic acetamide compound of the present invention has a dopamine D1 receptor positive allosteric modulating activity and can be used as an agent for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like.
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Synthesis of autophagy inducing compound and the uses thereof (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to a composition comprising compound of formula CB6 or CB8,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="89.24mm" wi="63.92mm" file="US09604987-20170328-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> the pharmaceutically-acceptable carrier, solvent, the salts thereof or a combination thereof which is used to treat autophagy-associated diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, etc. The present invention also relates to a method of treating these diseases by administering a therapeutically-effective amount of the compound to the subject in need of the treatment. The present invention further relates to the use of this compound in preparation of the composition to treat the diseases. </p>
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Ghrelin splice variant for treating neuronal damage, neurodegenerative disease, Parkinsons disease, Alzheimers disease, and/or depression (Fri, 19 Feb 2016)
The present disclosure relates, in one aspect, to use of ghrelin splice variant or an analogue thereof, or a ghrelin splice variant-like compound for the preparation of a medicament for one or more of: treatment and/or prevention of neuronal damage and/or neurodegeneration and, prophylaxis or treatment of neuronal damage and/or neurodegenerative disease, Parkinson's disease, Alzheimer's disease, depression stimulation of neuronal activity. A further aspect relates to a number of new ghrelin splice variant-like compounds and uses thereof, as well as to pharmaceutical compositions and medical packaging comprising the new ghrelin splice variant-like compounds.
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Compounds and their use as BACE inhibitors (Fri, 12 Feb 2016)
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 AD-related pathologies such as Down's syndrome, j-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
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2-Halo-5-Alkynyl-Pyridyl Nicotinic Ligands (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">Disclosed are heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. The compounds are useful for treating a mammal suffering from any one of a range of therapeutic indications, including Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism, trichotillomania, and hypothermia.</p>
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Benzimidazole derivatives and uses thereof (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and pharmaceutical compositions thereof. The present invention also provides methods and kits using the inventive compounds and pharmaceutical compositions for treating and/or preventing diseases associated with protein aggregation, such as amyloidoses (e.g., Parkinson's disease and Alzheimer's disease), treating and/or preventing neurodegenerative diseases, treating and/or preventing diseases associated with Tar DNA binding protein 43 kDa, reducing or preventing protein aggregation, and/or modulating E3 ubiquitin ligase in a subject in need thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.68mm" wi="75.01mm" file="US09790188-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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6-AMINO-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL OR 3-AMINOCHROMAN-7-YL DERIVATIVES AS TAAR MODULATORS (Fri, 05 Feb 2016)
The present invention relates to a compound of formula (I), wherein L is –C(O)NH-, -NHC(O)-, -S(O)2NH-, -NH- or -NHC(O)NH-; Ar is phenyl, benzyl, naphthyl or heteroaryl, selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, isoxazolyl or pyrazinyl, wherein Ar may be optionally substituted by one, two or three R1; R1 is hydrogen, lower alkyl, lower alkoxy, halogen, cyano, cycloalkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen, or is phenyl optionally substituted by one or two halogen atoms, CF3O or lower alkyl, or is furanyl, thiazolyl or thiophenyl, optionally substituted by halogen or lower alkyl; X is CH or O; R is hydrogen or halogen; or a pharmaceutically suitable acid addition salt thereof, all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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2-OXA-5-AZABICYCLO[2.2.1]HEPTAN-3-YL DERIVATIVES (Fri, 05 Feb 2016)
The present invention relates to compounds of formula (I), wherein L is a bond, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, CH2C(O)NH-, -CH2NH-, -NH- or -NHC(O)NH-; R1 is hydrogen, lower alkyl, halogen, lower alkoxy-alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen or is phenyl or heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl or pyrazolyl, and wherein phenyl and heteroaryl are optionally substituted by one, two or three substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cycloalkyl or O-CH2-cycloalkyl; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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PPAR-sparing compounds for the treatment of metabolic diseases (Fri, 05 Feb 2016)
The present invention relates to hydroxamate compounds and pharmaceutical compositions that are useful for treating and/or preventing metabolic inflammation mediated diseases such as diabetes, obesity, hypertension, dyslipidemia, a neurodegenerative disorder (e.g., Alzheimer's disease, Parkinson's disease, or Huntington's disease), or any combination thereof. Moreover, the present invention also provides methods of treatment for these diseases or disorders.
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INHIBITORS OF LRRK2 KINASE ACTIVITY (Fri, 29 Jan 2016)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula I. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="55.37mm" file="US20160024071A1-20160128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS (Thu, 28 Jan 2016)
The present invention provides compositions and methods useful for treating and preventing neurodegenerative disease and neurologically related disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing diseases and disorders with abnormal blood brain barrier (BBB) function, for example neurodegenerative diseases with a permeable BBB, such as but not limited to, Alzheimer's Disease, Huntington's Disease, Parkinson's Disease and Vascular Dementia.
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P2X7 MODULATORS (Fri, 22 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to a compound of Formula (I) Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) and methods comprising administering to a subject at least one compound selected from compounds of Formula (I) for treating diseases mediated by P2X7 receptor activity, such as rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuro-immune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomerulonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, <i>chlamydia</i>, neuroblastoma, Tuberculosis, and migraine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.40mm" wi="62.40mm" file="US20160016962A1-20160121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.</p>
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.</p>
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.</p>
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Compounds inhibiting leucine-rich repeat kinase enzyme activity (Fri, 15 Jan 2016)
<p id="p-0001" num="0000">The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK2 kinase is involved.</p>
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SUBSTITUTED INDAZOLE OR INDOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS (Thu, 14 Jan 2016)
Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson's disease, Alzheimer's disase and dementia
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COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Thu, 14 Jan 2016)
The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK2 kinase is involved.
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COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Thu, 14 Jan 2016)
The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.
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COMT inhibitors (Fri, 08 Jan 2016)
<p id="p-0001" num="0000">The present invention relates to compounds of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US09656971-20170523-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein the substituents are described in claim <b>1</b> and to the pharmaceutically acceptable salts thereof. </p> <p id="p-0003" num="0000">These compounds inhibit the enzyme catechol-O-methyltransferase (COMT). The compounds may be used for the treatment of Parkinson's disease, depression, cognitive impairment and motor symptoms, resistant depression, cognitive impairment, mood and negative symptoms of schizophrenia.</p>
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Substituted pyrrolo[2,3-d]pyrimidines as LRRK2 inhibitors (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">The present invention provides novel 4,5-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.74mm" wi="54.53mm" file="US09642855-20170509-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy. </p>
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N-substituted-5-substituted phthalamic acids as sortilin inhibitors (Fri, 25 Dec 2015)
<p id="p-0001" num="0000">The present invention is directed to N-substituted-5-substituted phthalamic acids which of formula (A). The compounds are considered useful for the treatment of diseases treatment of a neurodegenerative disease, psychiatric disease, motorneuron disease, peripheral neuropathies, pain, neuroinflammation or atherosclerosis such as Alzheimer's disease and Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="54.53mm" file="US09682967-20170620-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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QUINAZOLINONE COMPOUNDS (Fri, 18 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to quinazolinone compounds, processes for their preparation and their use as pharmaceutical agents for the treatment of Parkinson's disease (PD). The quinazolinone compounds are of general formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="38.69mm" file="US20150359796A1-20151217-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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LRRK2 GTP binding inhibitors for treatment of Parkinson's disease and neuroinflammatory disorders (Fri, 18 Dec 2015)
<p id="p-0001" num="0000">Compounds, and methods of using the same, are provided as therapies for the treatment leucine-rich repeat kinase-2 (LRRK2)-related disorders including, but not limited to, neurodegenerative and neuroinflammatory disorders, such as Parkinson's Disease.</p>
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ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF (Fri, 18 Dec 2015)
Disclosed are compounds of Formula (IVA), or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof: Formula (IVA), wherein "RIa", "RIb", "RIc", "RId", "RIe", are defined herein above, which compounds are believed suitable for use in positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) receptors, for example, those found in the cerebral cortex and the hippocampus. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Alzheimer's disease (AD), schizophrenia, and Parkinson's disease (PD), or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
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4-(5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)-1,4-dimethyl-1H-pyrrol-3-yl)benzenesulfonamide as alpha 7 nAChR modulator (Fri, 18 Dec 2015)
Disclosed are an alpha 7 nAChR receptor modulator compound, 4- (5-(4-chlorophenyl)-2-(2-cyclopropylacetyl)- 1,4-dimethyl- lH-pyrrol-3- yljbenzenesulfonamide, its tautomeric form, its pharmaceutically acceptable salts, pharmaceutical compositions comprising the compound or a salt thereof, and a method of treating various diseases, disorders or conditions, for example, Alzheimer's disease, mild cognitive impairment, senile dementia, vascular dementia, dementia of Parkinson's disease, and attention deficit disorder.
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Substituted indazole derivatives as in vitro MAO-B inhibitors (Fri, 11 Dec 2015)
<p id="p-0001" num="0000">Substituted indazole or imidazole derivatives of formula I as an in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and dementia.</p>
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Steroidal nitrones for the treatment and prevention of a cerebral stroke or ischaemia, Alzheimer and Parkinson disease and amyotrophic lateral sclerosis (Fri, 11 Dec 2015)
The invention relates to neuroprotective, antioxidant steroidal nitrones to which the blood-brain barrier is highly permeable, as potential drugs for the treatment of a cerebral stroke or ischaemia, Alzheimer and Parkinson disease and amyotrophic lateral sclerosis.
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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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Heteroaromatic compounds and their use as dopamine D1 ligands (Fri, 04 Dec 2015)
<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="34.71mm" wi="62.15mm" file="US09527843-20161227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and pharmaceutically acceptable salts thereof and N-oxides of the foregoing; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, salts or N-oxides, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCI, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, and bipolar disorder. </p>
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Hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 04 Dec 2015)
<p id="p-0001" num="0000">The present invention relates to novel 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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5-OXA-2-AZABICYCLO[2.2.2]OCTAN-4-YL AND 5-OXA-2-AZABICYCLO[2.2.1]HEPTAN-4-YL DERIVATIVES AS TAAR1 MODULATORS (Fri, 04 Dec 2015)
The invention relates to compounds of formula (I) wherein.....C.....is -CH2- or -CH2-CH2-; X is -NH-, -C(0)NH- or -NHC(0)NH-; Ar is phenyl or a 5 or 6-membered heteroaryl group containing one or two N atoms; R1 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by cycloalkyl, lower alkoxy substituted by halogen or is cycloalkyl; -( )- is -CH2-; n is 0 or 1; m is 0, 1 or 2; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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DIKETONES AND HYDROXYKETONES AS CATENIN SIGNALING PATHWAY ACTIVATORS (Fri, 04 Dec 2015)
[0279] The present invention discloses -diketones, y-diketones or 7 hydroxyketones or analogs thereof, that activate Wnt/p-catenin signalling 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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(4E)-4-(4-substituted benzylideneamino)-2,3-dihydro-3-substituted-2-thioxothiazole-5-carbonitriles as A2AR antagonist and process for preparation thereof (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">The present invention provides (4E)-4-(4-substituted benzylideneamino)-2,3-dihydro-3-substituted-2-thioxothiazole-5-carbonitriles of general formula A, below, and a process for the preparation thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.71mm" wi="68.33mm" file="US09518033-20161213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> The compounds of present invention are useful in the treatment of central nervous disorders including, Parkinson disease, Huntington's disease, attention disorder, cognition, Alzheimer disease, depression and hypertension. </p>
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Aminopyridine derived compounds as LRRK2 inhibitors (Fri, 27 Nov 2015)
<p id="p-0001" num="0000">The present invention is directed to aminopyridine derived compounds of formula (A). The compounds are considered useful for the treatment of diseases associated with LRRK2 such a Lewy body dementia, Parkinson's disease or cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="69.85mm" file="US09321748-20160426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INDOLIN-2-ONE AND 1,3-DIHYDRO-PYRROLO[3,2-c]PYRIDIN-2-ONE DERIVATIVES (Fri, 27 Nov 2015)
The present invention is concerned with indolin-2-one and l,3-dihydro-pyrrolo[3,2-c]pyridin-2-one derivatives of general formula (I) wherein Ar1 is phenyl, pyridinyl or pyrimidinyl; Ar2 is a 5 or 6 membered heteroaryl group, containing 2 or 3 heteroatoms, selected from N, O or S; R1 is hydrogen, lower alkyl, halogen or lower alkoxy; R2 is hydrogen or lower alkyl; R3 is hydrogen, lower alkyl, lower alkyl substituted by hydroxy, cycloalkyl, oxetan-3-yl, pyridinyl, imidazolyl, pyrazolyl, pyrimidinyl, which rings may optionally substituted by lower alkyl, or is -(CH2)3-S(O)2-cyclopropyl; X is CH or N; n is 1 or 2; as well as with a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof, for use in the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.
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3,4-dihydroisoquinolin-2(1H)-yl compounds (Fri, 20 Nov 2015)
The invention provides certain 3,4-dihydroisoquinolin-2(1H)-yl compounds, particularly compounds of formula (I), and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula (I) to treat cognitive impairment associated with Parkinson's disease or schizophrenia.
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4-amino-6-phenyl-5,6-dihydroimidazo[1,5-a]pyrazin-3(2H)-one derivatives as inhibitors of beta-secretase (BACE) (Fri, 20 Nov 2015)
The present invention relates to novel 5,6-dihydroimidazo[1,5-a]pyrazin-3(2<i>H</i>)-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes and other metabolic disorders.
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4-amino-6-phenyl-6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazine derivatives as inhibitors of beta-secretase (BACE) (Fri, 13 Nov 2015)
The present invention relates to novel 6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazin- 6-yl derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, in particular BACE1 and/or BACE2 (wherein BACE1, is also known as Asp2, or memapsin2 and BACE2 is also known as Asp1, Memapsin 1 or DRAP). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia of the Alzheimer's type, dementia associated with beta-amyloid, age- related macular degeneration, type 2 diabetes and other metabolic disorders.
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