Alzheimer's disease

CHEMCICAL COMPOUNDS (Fri, 15 Dec 2017)
The invention is directed to substituted pyrrolidine derivatives. Specifically, the invention is directed to compounds according to Formula III: wherein A, B, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, R10, R30, Y1, Y2, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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CHEMICAL COMPOUNDS AS ATF4 PATHWAY INHIBITORS (Fri, 15 Dec 2017)
The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: wherein A, B, X, Y, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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COMPOUNDS (Fri, 08 Dec 2017)
The present technology relates to compounds, kits, compositions, and methods useful for the treatment of numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, defective wound healing, and/or sensorineural hearing and vision loss.
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METHOD FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES (Fri, 24 Nov 2017)
Disclosed is an in vitro method for the determination of neurodegenerative diseases, in particular Parkinson's disease and Alzheimer's disease, based on measuring, in a peripheral blood sample, the heteromeric complexes of a-synuclein with β-amyloid 1-42 and a-syn with tau protein. Further subjects of the invention are an immunochemical assay for the quantitation of said heteromeric complexes and a diagnostic kit for conducting the assay.
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OXOINDOLINE DERIVATIVES AS PROTEIN FUNCTION MODULATORS (Fri, 24 Nov 2017)
The present invention provides chimeric compounds of formula (II) that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CKl-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.
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CAMSYLATE SALT (Fri, 24 Nov 2017)
A camsylate salt of (1r,1'R,4R)- 4-methoxy-5 "-methyl-6'-[5 -(prop-i -yn- 1 -yl)pyridin-3 -yl] 3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine, pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating AB-related pathologies such as Alzheimer's Disease, Down's syndrome, B-amyloid angiopathy and conditions such as dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
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4H-pyran compounds as insulin-regulated aminopeptidase (IRAP) inhibitors (Fri, 24 Nov 2017)
The present disclosure relates to <i>4H</i>-pyran compounds of formula (I) and their use in therapy, to compositions and agents comprising said compounds, to methods of treatment using said compounds, and their use in the manufacture of medicaments. The disclosure further relates to said compounds and compositions thereof as inhibitors of IRAP and their use in the treatment or prevention of Alzheimer's disease and the treatment and prevention of memory and cognitive disorders.
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INHIBITION OF BETA-2 NICOTINIC ACETYLCHOLINE RECEPTORS TO TREAT ALZHEIMER'S DISEASE PATHOLOGY (Fri, 17 Nov 2017)
The invention provides methods of reducing development of mild cognitive impairment and/or learning disorders and/or memory disorders in a subject suspected to have or suffering from Alzheimer's disease (AD). In some embodiments,the methods comprise administering a therapeutically effective amount of a beta-2 nicotinic acetylcholine receptor (n AChR) antagonist and/or beta-2 nAChRnegative allosteric modulator (NAM) to the subject over a therapeutic dosing period to thereby reduce the rate of development of mild cognitive impairment and/or learning disorders and/or memory disorders in the subject over the therapeutic dosing period.
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COMPOUNDS TO PROMOTE NORMAL PROCESSING OF APP (Fri, 17 Nov 2017)
In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of compound C41 to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly enhances sAPPα, lowers Aβ, p-Tau, inhibits the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) and improves memory in a mammal are provided.
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ISOTOPICALLY MODIFIED COMPOSITION AND THERAPEUTIC USES THEREOF (Fri, 10 Nov 2017)
This disclosure relates to isotopically modified amino acids and their pharmaceutical or nutritional uses in stabilizing pharmaceutical protein-based formulations, proteins with long life span, and preventing or treating disease such as Alzheimer's disease. Specifically, the disclosure provides protein drugs having increased stability comprising an L-aspartate (L-Asp) residue or an L-asparagine (L-Asn) residue, wherein the L-Asp residue or the L-Asn residue comprises a deuterium atom.
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MOFEZOLAC DERIVATIVES AS MULTI-FUNCTIONS SELECTIVE COX-1 INHIBITORS (Fri, 03 Nov 2017)
The invention relates to a new class of compounds of formula (I) targeting COX-1. The invention also relates to the use of some of such compounds as a tool to investigate the structure and function of the enzyme, in the treatment targeting COX-1 or detection of COX-1 in relating disorders or diseases such as cancer and neuroinflammation, in particular in neurological (e.g. autism spectrum disorders) and neurodegenerative diseases (e.g. Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury (TBI), HIV dementia and prion diseases), and in gynecological tumour (e.g. ovarian cancer), neck and head tumor, and haematological tumours (e.g. multiple myeloma) and in the detection of COX-1 in "in vitro" (cells and tissues) and in "in vivo".
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.
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PRODRUG OF AMINO ACID DERIVATIVE (Fri, 27 Oct 2017)
Provided is an amino acid derivative prodrug represented by general formula (I-A) that is a prodrug form of an amino acid derivative which is a group 2 metabotropic glutamate receptor antagonist, or a pharmaceutically acceptable salt thereof. More specifically, provided is an amino acid derivative prodrug represented by general formula (I-A) that is a preventive or therapeutic drug for mood disorders (including depression and bipolar disorder), anxiety disorder, cognitive disorders, developmental disorders, Alzheimer's disease, Parkinson's disease, movement disorders associated with muscular rigidity, sleep disorders, Huntington's chorea, eating disorders, drug dependence, epilepsy, brain infarction, cerebral ischemia, cerebral insufficiency, cerebral edema, spinal cord disorders, head trauma, inflammation and immune- related diseases, and so on.
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SELECTIVE D3 DOPAMINE RECEPTOR AGONISTS AND METHODS OF THEIR USE (Fri, 20 Oct 2017)
The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.
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COMPOUNDS AND COMPOSITIONS FOR THE DETECTION AND TREATMENT OF ALZHEIMER'S DISEASE AND RELATED DISORDERS (Thu, 19 Oct 2017)
One aspect of the present invention relates to compounds of formula (II), compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.
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NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS (Fri, 13 Oct 2017)
Neuropeptide S receptor agonists are provided. The NPS agonists include peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.
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NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS (Fri, 13 Oct 2017)
Neuropeptide S receptor agonists are provided. The NPS agonists include trimeric, tetrameric, pentameric or hexameric peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The peptidomimetic molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.
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PROCESS FOR LARGE SCALE PRODUCTION OF 1-ISOPROPYL-3--1H-INDAZOLE OXALATE (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a process suitable for adoption to large scale manufacture of 1-isopropyl-3-{5-[1-(3-methoxypropyl)piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate of formula (I), which is a selective 5-HT<sub>4 </sub>receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.</p>
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HETEROCYCLIC COMPOUND (Fri, 06 Oct 2017)
<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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ALKYLIDENE PHOSPHONATE ESTERS AS P-GLYCOPROTEIN INDUCERS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to the alkylidene phosphonate esters of formula I wherein, R<sub>1 </sub>is selected from a group consisting of hydrogen or alkyl group; R<sub>2 </sub>is selected from a group consisting of hydrogen, hydroxy, alkyl, alkoxy, nitro, halogen, amino, N-substituted alkylamino; alkyl group is selected from a group consisting of methyl, ethyl and isopropyl; Ar is selected from a group consisting of aryl, substituted aryl, fused aryl, heteroaryl, and substituted heteroaryl. The present invention particularly relates to synthesis and p-glycoprotein induction activity of the alkylidene phosphonate esters. In addition, the invention relates to methods of using compounds for treating or preventing Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="52.24mm" file="US20170275314A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula I: R1-L1-C(A)(A′)-CH<sub>2</sub>, -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.</p>
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ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.65mm" wi="69.85mm" file="US20170275260A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Dosing Regimens for Treating And/Or Preventing Cerebral Amyloidoses (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).</p>
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Pharmaceutical compounds and use of same in cancer and tauopathies (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (l)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.</p>
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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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M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS AND METHODS OF USE THEREOF (Fri, 22 Sep 2017)
The present invention is directed to compounds of general formula (I) or pharmaceutically acceptable salts thereof, which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, or pharmaceutically acceptable salts thereof, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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COMBINATION OF A BACE INHIBITOR AND AN ANTIBODY OR ANTIGEN-BINDING FRAGMENT FOR THE TREATMENT OF A DISORDER ASSOCIATED WITH THE ACCUMULATION OF AMYLOID BETA (Fri, 22 Sep 2017)
The present disclosure provides for methods for treating a subject having a disease or disorder associated with the accumulation of amyloid beta, comprising administering to the subject a BACE inhibitor and an antibody or antigen-binding fragment that binds to amyloid beta n-42. In some embodiments, the disease or disorder is Alzheimer's Disease.
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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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DETECTION OF NEURODEGENERATIVE DISEASES (Fri, 15 Sep 2017)
The present invention relates to novel compounds, their uses as biomarker, and/or methods including a non-invasive in vitro method using this biomarker, for diagnosing or monitoring the development or the progression of Alzheimer's disease (AD) or a disease or disorder associated with β-amyloid peptide (Aβ) deposition or tau hyperphosphorylation or a disease or disorder characterized by a proteinopathy implicating abnormalities in protein kinase C (PKC).
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QUINAZOLINE COMPOUNDS USEFUL AS M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 15 Sep 2017)
The present invention is directed to compounds of Formula (I): (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R7, R8, R9, R11, n and p are defined herein. The compounds of Formula (I) are M1 receptor positive allosteric modulators that are useful in the treatment of diseases in which the M1 receptor is involved, including Alzheimer's disease, schizophrenia, pain and sleep disorders. The invention also relates to pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, and to methods of using the compounds of Formula (I) in the treatment of diseases mediated by the M1 receptor.
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BACE 1 INHIBITORS (Sat, 09 Sep 2017)
The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compound of the present invention is useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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PIPERIDINE DERIVATIVE AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention provides N-[1-(1-Cyclohexyl-3,5-dimethyl-1H-pyrazole-4-sulfonyl)-4-phenyl-piperidin-4-ylmethyl]-N-isobutyl-4-{[(piperidin-4-ylmethyl)-amino]-methyl}-benzenesulfonamide and pharmaceutically acceptable salts thereof. These compounds may be useful in the treatment of diseases such as Alzheimer's disease or renal failure. The present invention further relates to methods for the preparation of compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the use of such compounds and/or pharmaceutical compositions in treating certain diseases.
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M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR COMPOUNDS AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention is directed to compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Q, X, Y, Z, R1, R7 and n are defined herein. The compounds of Formula (I) are M1 receptor positive allosteric modulators that are useful in the treatment of diseases in which the M1 receptor is involved, including Alzheimer's disease, schizophrenia, pain and sleep disorders. The invention also relates to pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, and to methods of using the compounds of Formula (I) in the treatment of diseases mediated by the M1 receptor.
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NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention aims to provide a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease, which has a novel action mechanism and shows less side effects. A polyphenol derivative having liposolubility enhanced by the introduction of at least one kind of a liposoluble group selected from the group consisting of a chain saturated hydrocarbon group, a chain unsaturated hydrocarbon group, a cyclic saturated hydrocarbon group, a cyclic unsaturated hydrocarbon group, an aromatic hydrocarbon group, a liposoluble vitamin residue and a sterol residue has an action to potentiate neprilysin activity, and is useful as a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease.</p>
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Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof (Fri, 08 Sep 2017)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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GLYCOSIDASE INHIBITORS (Fri, 01 Sep 2017)
Compounds of formula (I) wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
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GLYCOSIDASE INHIBITORS (Fri, 01 Sep 2017)
Compounds of formula (I) wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
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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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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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Curcumin analogs (Wed, 23 Aug 2017)
<p id="p-0001" num="0000">Provided herein are curcumin analogues that are able to interact with amyloid β (Aβ) and to attenuate the copper-induced crosslinking of Aβ. Also provided herein are methods of using the compounds in the treatment of Alzheimer's Disease or a related disorder.</p>
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METHODS OF SYNTHESIZING GAMMA-AAPEPTIDES, GAMMA-AAPEPTIDE BUILDING BLOCKS, GAMMA-AAPEPTIDE LIBRARIES, AND GAMMA-AAPEPTIDE INHIBITORS OF ALPHA-BETA40 AGGREGATES (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Embodiments of the present disclosure provide for γ-AApeptides, γ-AApeptide building blocks, methods of making γ-AApeptides and libraries of γ-AApeptides, methods of screening the γ-AApeptide libraries for desired peptidomimetic activity, and the like. The present disclosure also provides for γ-AApeptides that are inhibitors of Aβ peptide aggregation, methods of inhibiting and disassembling Aβ peptide aggregation, methods of inhibiting the toxicity of Aβ aggregates towards N2a neuroblasotma cells, as well as methods and compounds for treating Alzheimer's disease.</p>
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Tetrahydropyrrolo[3,4-D][1,3]thiazine-derivative as BACE inhibitor (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention provides a compound of Formula I: which is crystalline. The compound of Formula (I) is useful in the treatment of Alzheimer's disease (BACE inhibitor).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.44mm" wi="71.97mm" file="US09828390-20171128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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C5-C6-OXACYLIC FUSED IMINOTHIAZINE DIOXIDE COMPOUNDS BEARING AN ETHER LINKER AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 18 Aug 2017)
In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminothiazine dioxide compounds bearing an ether linker, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, R2, R3, RA, ring A, m, n, -L1-, ring B, RB, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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C5-C6-OXACYLIC FUSED IMINOTHIADIAZINE DIOXIDE COMPOUNDS BEARING AN ETHER LINKER AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 18 Aug 2017)
In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminothiadiazine dioxide compounds bearing an ether linker, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein RN, R1, R2, RA, ring A, ring C, and m are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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APOE4-TARGETED THERAPUTICS THAT INCREASE SIRT1 (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">A link between ApoE4 allele and sirtuins expression level is identified that is believed to be associated with elevated risk for the promotion of processing of amyloid precursor protein (APP) by the non-amyloidogenic pathway in a mammal leading to elevated risk for Alzheimer's disease. Compounds are identified that upregulate sirtuins (e.g., SirT1) expression levels and appear to be useful in the treatment and/or prophylaxis of MCI and/or Alzheimer's disease.</p>
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PIPERAZINE DERIVATIVES AS LIVER X RECEPTOR MODULATORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are liver X receptor modulators, and which are useful in the treatment of diseases and disorders associated with the liver X receptor. Also provided are the compounds of Formula (I) and pharmaceutical compositions thereof for treating atherosclerosis, cardiovascular disease, Alzheimer's disease, dermatitis, dyslipidemia, cancer and other diseases or disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="60.45mm" file="US20170226067A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2,2,2-TRIFLUOROETHYL-THIADIAZINES (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="57.15mm" file="US20170226091A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL 3-AMINO-PYRROLO[3,4-C]PYRAZOLE-5(1H, 4H,6H) CARBALDEHYDE DERIVATIVES (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="92.03mm" wi="69.93mm" file="US20170217991A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A, B, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, R<sup>9 </sup>and R<sup>10 </sup>are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disase pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.</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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METHODS FOR SCREENING THERAPEUTIC AGENT FOR PROTEIN CONFORMATIONAL DISEASES (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Provided is a screening method of a composition for preventing or treating various protein conformational diseases including Alzheimer's disease, and the screening method of a composition for diagnosing protein conformational diseases. The screening method according to the present invention can rapidly mass-screen the composition for treating or diagnosing the protein conformational diseases in silico with highly reliability based on the binding of the peptide of the present invention and the test material.</p>
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Methods for Diagnosing Alzheimer's Disease (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">A method of diagnosing Alzheimer's disease and/or dementia in a subject comprising: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">a) determining and/or characterizing the telomeric organization of cells in a test sample from the subject; <br/> wherein a difference in the telomeric organization, for example the number and/or length of telomeres in the test sample cells compared to a control is indicative the subject has Alzheimer's disease and/or dementia or an increased risk of developing Alzheimer's disease and/or dementia. </li> </ul> </li> </ul> </p>
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Compounds (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit Lp-PLA<sub>2 </sub>activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA<sub>2</sub>, for example Alzheimer's disease.</p>
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Compounds (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit Lp-PLA<sub>2 </sub>activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA<sub>2</sub>, for example atherosclerosis, Alzheimer's disease.</p>
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DIHYDROPYRIDO QUINAZOLINE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 21 Jul 2017)
Disclosed herein are compounds of formula (I), which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases, in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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FLAVONOIDE-TYPE COMPOUNDS BEARING AN O-RHAMNOSYL RESIDUE (Fri, 21 Jul 2017)
The present invention relates to compounds of formula (I) These compounds are useful in the treatment of many diseases such as a skin disease, an allergy, an autoimmune disease, a cardiovascular disease, a lung disease, asthma, a bacterial, viral or parasitic disease, metabolic syndrome, cancer, Alzheimer's disease or diabetes and are furthermore useful in the preparation of cosmetics and for use in food and animal feed.
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SALT FORMS OF [R-(R*,R*)]-2-(4-FLUOROPHENYL)-BETA,DELTA-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">Novel salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid characterized by their X-ray powder diffraction pattern and solid-state NMR spectra are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.</p>
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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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Difluoromethoxy compound with low bioactivation potential for the reduction of beta-amyloid production (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The compound N2-(3-(difluoromethoxy)-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-7-(4-fluorophenyl)-N4,5,5-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine: [PLEASE INSERT CHEMICAL STRUCTURE HERE] reduces -amyloid peptide (A 42) production and has low potential for bioactivation, and may be useful in the treatment of Alzheimer's Disease and other conditions affected by -amyloid peptide (A 42) production.</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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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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TETRAHYDROQUINOXALINE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 16 Jun 2017)
The present invention is directed to tetrahydroquinoxaline compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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TREATMENT OF HOT FLUSHES, VASOMOTOR SYMPTOMS, AND NIGHT SWEATS WITH SEX STEROID PRECURSORS IN COMBINATION WITH SELECTIVE ESTROGEN RECEPTOR MODULATORS (Thu, 15 Jun 2017)
Novel methods for reduction or elimination of the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly benzopyran compounds. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.
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C5-C6-CARBOCYCLIC FUSED IMINOTHIADIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 09 Jun 2017)
In its many embodiments, the present invention provides certain C5-C6-carbocyclic fused iminothiazine dioxide compounds, including compounds Formula (I): and tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, ring A, RA, m, -L1-, ring B, RB, n, q, ring C, RC, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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HOMOBISPIPERIDINYL DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 09 Jun 2017)
In its many embodiments, the present invention provides certain substituted bispiperidinyl compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein ring A, ring B, R1, R2, R3, L, R4, X, Z, Li, Q and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver Χ-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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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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Compounds, Compositions, and Methods for Treating Alzheimer's Disease (Fri, 02 Jun 2017)
<p id="p-0001" num="0000">Novel methods and compounds for treating Alzheimer's Disease are provided. In one aspect, the invention provides methods for treating Alzheimer's Disease by administering certain phenothiazine derivatives. In one embodiment, the methods include administering an effective amount of a 3-oxo-7-dialkyl-amino-phenothiazine derivative, or 3-oxo-7-dialkyl-amino-phenothiazine. In another embodiment, the invention provides methods for treating Alzheimer's Disease by administering an effective amount of a 3,7-diazetidin-1-yl-phenothiazine or a derivative thereof. In another aspect, the invention provides novel azetidinyl phenothiazine compounds.</p>
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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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PYRROPYRIMIDINE COMPOUNDS AS MNKS INHIBITORS (Sat, 27 May 2017)
The present invention relates to compounds of formulae I, or pharmaceutically acceptable salts or esters thereof, wherein: R1 is selected from H and CO-NR8R9, wherein R8 and R9 are each independently selected from H, alkyl, cycloalkyl and mono or bicyclic heterocycloalkyl, wherein said alkyl group is optionally substituted by one or more R12 groups, and said heterocycloalkyl is optionally substituted by R10 or R12; or R8 and R9 are linked, together with the nitrogen to which they are attached, to form a heterocycloalkyl group optionally containing one or more additional heteroatoms, and optionally substituted by one or more groups select from R10 and (CH2)mR12; R2 is selected from H and alkyl, wherein said alkyl group is optionally substituted by one or more R12 groups; R3 is selected from alkyl, cycloalkyl and heterocycloalkyl, each of which may be optionally substituted by halo, OH or alkoxy; Z1, Z2, Z3 and Z4 are all C; R4, R5, R6 and R7 are each independently selected from H, alkyl, CN, NO2,OH, alkoxy, NHCO-alkyl, halo and haloalkyl; or Ζ1, Z3 and Z4 are ail C, Z2 is N, R5 is absent and R4, R6 and R7 are as defined above; or Z1, Z3 and Z4 are all C, Z1 is N, R4 is absent and R5, R6 and R7 are as defined above; each R10 and R11 is independently alkyl; each R12 is independently selected from CO2R10, COOH, OH, alkoxy, haloalkyl, NH2, NHR10, NR10R11, heteroaryl and heterocycloalkyl; R13 is H or halo. Further aspects relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.
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FUSED THIAZOLOPYRIMIDINE DERIVATIVES AS MNKS INHIBITORS (Sat, 27 May 2017)
The present invention relates to compounds of formulae I and H, or pharmaceutically acceptable salts or esters thereof. Further aspects of the invention relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer'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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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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Systems, Assays, and Methods for Determining Risk Factors for Alzheimer's Disease (Fri, 19 May 2017)
<p id="p-0001" num="0000">A method of determining risk factors for Alzheimer's disease in an individual, including assaying a biological medium obtained from the individual for a biomarker selected from Biomarker 1, Biomarker 2, Biomarker 3, or Biomarker 4, where Biomarker 1 has a mass-to-charge ratio (m/z) of 602.3, Biomarker 2 has a m/z of 804.6, Biomarker 3 has a m/z of 874.6, and Biomarker 4 has a m/z of 804.5, and where the presence of the two or more biomarkers in the individual indicates a risk factor of Alzheimer's disease.</p>
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CYANOPYRIDINE DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 19 May 2017)
In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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BISPIPERIDINYL DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 19 May 2017)
In its many embodiments, the present invention provides certain substituted bispiperidinyl compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, Q and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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INHIBITORS OF ARGININE GINGIPAIN (Fri, 19 May 2017)
The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its proteases arginine gingipain A/B (Rgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.
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NITROGENATED HETEROCYCLIC COMPOUND (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a PDE2A selective inhibitory action, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like.</p> <p id="p-0002" num="0000">The present invention is a compound represented by the formula (1):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.14mm" wi="69.85mm" file="US20170129887A1-20170511-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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THERAPEUTIC AGENT FOR DISEASES ASSOCIATED WITH NERVE AXON DYSFUNCTION, INCLUDING THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE (Fri, 12 May 2017)
<p id="p-0001" num="0000">Provided are a clinically applicable drug for radical cure of Alzheimer's disease (AD), and a drug for treating neurological diseases associated with axonal dysfunction other than AD, wherein the drug utilizes the mechanism of action of the AD radical cure therapy. The drugs are oral drugs, each comprising one or more compounds selected from diosgenin, a diosgenin derivative and a pharmaceutically acceptable salt thereof, the one or more compounds being suspended in an edible oil.</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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Pyrrolo[2,3-C]pyridines as imaging agents for neurofibrillary (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.45mm" wi="59.44mm" file="US09808542-20171107-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMBINATION THERAPY (Fri, 05 May 2017)
The present invention relates to the use of anti-Aβ antibodies and serum amyloid P component (SAP) depleting compounds in the treatment of diseases associated with amyloid deposition, such as Alzheimer's disease.
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NOVEL FLUORINATED HETEROCYCLE DERIVATIVES AND THEIR USES AS THERAPEUTIC AGENTS (Fri, 05 May 2017)
The present application relates to novel fluorinated heterocycle derivatives or compounds of Formula (I), to processes for preparing them, pharmaceutical compositions containing them, and their use thereof in the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, epilepsy, schizophrenia, Alzheimer' disease, cognitive disorders and memory deficits, as well as chronic and acute pain and other related CNS disorders.
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FLUORINATED AMIDE DERIVATIVES AND THEIR USES AS THERAPEUTIC AGENTS (Fri, 05 May 2017)
The present application relates to novel fluorinated amide derivatives of Formula (I), to processes for preparing them, pharmaceutical compositions containing them, and their use thereof in the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, epilepsy, schizophrenia, Alzheimer' disease, cognitive disorders and memory deficits, as well as chronic and acute pain and other related CNS disorders.
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HETEROCYCLE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CNS DISORDERS (Fri, 05 May 2017)
The present application relates to novel heterocycle derivatives of Formula (I), to processes for preparing them, pharmaceutical compositions containing them, and their use thereof in the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, epilepsy, schizophrenia, Alzheimer' disease, cognitive disorders and/or memory deficits, as well as chronic and acute pain and other related CNS disorders.
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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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C2-carbocyclic iminothiazine dioxides as BACE inhibitors, compositions, and their use (Fri, 28 Apr 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C2-carbocyclic iminothiazine dioxide compounds, including compounds Formula (I); or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>1</sup>, R<sup>2</sup>, ring A, R<sup>A</sup>, m, ring B, RB, n, ring C, R<sup>C </sup>and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.33mm" wi="67.99mm" file="US09732088-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MRI METHOD FOR IN VIVO DETECTION OF AMYLOID AND PATHOLOGY IN THE ALZHEIMER BRAIN (Fri, 28 Apr 2017)
Disclosed are systems, biomarkers, and methods for the diagnosis of Alzheimer's Disease.
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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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Inhibitors of Jun N-terminal kinase (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="19.56mm" file="US09796706-20171024-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a salt or solvate thereof, wherein ring A, C<sup>a</sup>, C<sup>b</sup>, Z, R<sup>5</sup>, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease. </p>
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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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CRYSTALLINE ENCENICLINE HYDROCHLORIDE (Fri, 14 Apr 2017)
The present invention relates to a crystalline forms of encenicline hydrochloride and a process for their preparation. The invention also concerns a pharmaceutical compositions comprising an effective amount of the crystalline form of encenicline hydrochloride and at least one pharmaceutically acceptable excipient. The pharmaceutical composition of the present invention can be used as medicament, in particular for treatment and/or prevention of CNS disorders associated with cognitive deficits such as Alzheimer's disease and schizophrenia.
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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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PROCESS FOR THE PREPARATION OF ENCENICLINE FROM 7-CHLORO-BENZO[B]THIOPHENE-2-CARBOXYLIC ACID CHLORIDE AND (R)-QUINUCLIDIN-3-AMINE IN THE PRESENCE OF IMIDAZOLE (Fri, 14 Apr 2017)
The present invention relates to a process for the preparation of an amide from a carboxylic acid chloride and an organic molecule comprising both a primary amine group and a tertiary amine group, wherein the nitrogen atom of the tertiary amine group is comprised in a non-aromatic heterocycle and wherein the amide bond forms selectively with the primary amine group, comprising the step of reacting the carboxylic acid chloride with an organic molecule comprising both the primary amine group and the tertiary amine group, in the presence of imidazole. This is particularly useful in the preparation of amides from quinuclidin-3-amine, such as for the preparation of encenicline ((R) -7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide) from 7-chloro-benzo[b]thiophene-2-carboxylic acid chloride and (R)- quinuclidin-3-amine in the presence of imidazole. Encenicline is a nicotinic acetylcholine receptor agonist useful as a neuromodulator for the treatment of e.g. cognitive impairment, schizophrenia and Alzheimer's disease.
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CRYSTALLINE ENCENICLINE HYDROCHLORIDE (Thu, 13 Apr 2017)
The present invention relates to a crystalline form of encenicline hydrochloride and a process for its preparation. The invention also concerns a pharmaceutical composition comprising an effective amount of the crystalline form of encenicline hydrochloride and at least one pharmaceutically acceptable excipient. The pharmaceutical composition of the present invention can be used as medicament, in particular for treatment and/or prevention of CNS disorders associated with cognitive deficits such as Alzheimer's disease and schizophrenia.
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CRYSTAL FORMS OF A M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR (Fri, 07 Apr 2017)
The invention is directed to novel anhydrous crystalline butenedioate salt form 1 of Compound I, which is a modulator of muscarinic M1 receptors. The novel crystalline forms of compound I are useful in the treatment or prevention of Alzheimer's disease and other disorders and diseases in which muscarinic M1 receptors are involved. The invention is further directed to pharmaceutical compositions comprising the novel crystalline forms of Compound I.
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PROCESS FOR MAKING M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS (Fri, 07 Apr 2017)
This invention provides novel processes for the preparation of compounds such as 3-[(1S,2S)-2-hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]-quinazolin-4(3H)-one, salts and derivatives thereof. The compounds synthesized by the processes of the invention are useful for treating Alzheimer's disease and other diseases (e.g., cognitive impairment, schizophrenia, pain disorders, and sleep disorders) mediated by the muscarinic M1 receptor.
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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 PIPERAZINE AND PIPERIDINE DERIVATIVES, THEIR SYNTHESIS AND USE THEREOF IN INHIBITING VDAC OLIGOMERIZATION, APOPTOSIS AND MITOCHONDRIA DYSFUNCTION (Fri, 24 Mar 2017)
Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's disease.
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APP SPECIFIC BACE INHIBITORS (ASBIs) AND USES THEREOF (Fri, 24 Mar 2017)
In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASPI is a flavonoid (e.g. galangin) or flavonoid prodrug (e.g., galangin prodrug).
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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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LACTOFERRIN COMPOSITIONS AND METHODS FOR MODULATION OF T CELL SUBTYPES AND TREATMENT OF AUTOIMMUNE DISEASES (Fri, 17 Mar 2017)
Provided herein are improved compositions comprising lactoferrin and methods for modulating T cell subtypes and their activities in a subject, to improve the balance between anti¬ inflammatory (Th2) cytokine producing cells and pro-inflammatory (Thl) or Thl7 cells, and skew naive T cells toward a pro-regulatory phenotype, for the treatment and/or amelioration of neurodegenerative or autoimmune diseases and disorders (e.g., inflammatory bowel disease (IBD), amyotrophic lateral sclerosis (ALS), Alzheimers disease, cognitive decline in the elderly resulting from chronic inflammation, and/or rheumatoid arthritis (RA)).
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2-Amino-3,5,5-Trifluoro-3,4,5,6-Tetrahydropyridines as BACE1 Inhibitors for Treatment of Alzheimer's Disease (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.</p>
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Indazole inhibitors of the Wnt signal pathway and therapeutic uses thereof (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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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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SMALL MOLECULE INHIBITORS OF DYRK1A AND USES THEREOF (Fri, 10 Mar 2017)
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a benzimidazole or imidazopyridine structure which function as inhibitors of DYRK1A protein, and their use as therapeutics for the treatment of Alzheimer's disease, Down syndrome, glioblastoma, autoimmune diseases, inflammatory disorders (e.g., airway inflammation), and other diseases.
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Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use (Fri, 10 Mar 2017)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I): wherein variables A<sp>4</sp>, A<sp>5</sp>, A<sp>6</sp>, A<sp>8</sp>, and each of R<sp>a</sp>, R<sp>b</sp>, R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp> and R<sp>7</sp> of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.
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HYDROXYTRIAZINE COMPOUNDS AND PHARMACEUTICAL USE THEREOF (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and/or cancer including colorectal cancer.</p> <p id="p-0002" num="0000">The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof:</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="128.35mm" wi="74.08mm" file="US20170057943A1-20170302-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.</p>
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Process for large scale production of 1-isopropyl-3-{5- [1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}- 1h-indazole oxalate (Fri, 03 Mar 2017)
The present invention relates to a process suitable for adoption to large scale manufacture of l-IsopropyI-3-{5-[l1-(3-methoxypropyl) piperidin-4-yl]-[ 1,3,4] oxadiazol-2-yl}- 1H-indazole oxalate of formula (I), which is a selective 5-HT<sb>4</sb> receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.
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Piperazine derivatives as liver X receptor modulators (Fri, 03 Mar 2017)
Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are liver X receptor modulators, and which are useful in the treatment of diseases and disorders associated with the liver X receptor. Also provided are the compounds of Formula (I) and pharmaceutical compositions thereof for treating atherosclerosis, cardiovascular disease, Alzheimer's disease, dermatitis, dyslipidemia, cancer and other diseases or disorders.
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COMPOUNDS FOR THE REDUCTION OF ß-AMYLOID PRODUCTION (Thu, 02 Mar 2017)
The present disclosure provides a series of compounds of the formula (I), which modulate β-amyloid peptide (β-ΑΡ) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-ΑΡ) production.
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ISOLATED COMPOUNDS FROM TURMERIC OIL AND METHODS OF USE (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimer's disease are provided. Methods for treatment, inhibition, and/or abatement of cognitive decline and/or Alzheimer's disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.</p>
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TETRAHYDROOXEPINOPYRIDINE COMPOUND (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">[Problem] Provided is a compound having a positive allosteric modulating activity (PAM activity) on an α7 nicotinic acetylcholine receptor (α7 nACh receptor).</p> <p id="p-0002" num="0000">[Means for Solution] The present inventors have studied on a PAM activity on an α7 nACh receptor, and they have found that a tetrahydrooxepinopyridine compound has a PAM activity on an α7 nACh receptor, thereby completing the present invention. The tetrahydrooxepinopyridine compound of the present invention has a PAM activity on an α7 nACh receptor and can be expected as an agent for preventing or treating dementia, cognitive impairment, schizophrenia, Alzheimer's disease, CIAS, negative symptoms of schizophrenia, inflammatory diseases, or pain.</p>
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AMYLOID Precursor Protein (APP) Based β-Secretase Inhibitor Peptides, and Methods of Use (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention provides fusion peptides, compositions, methods and kits for treating, reducing the risk of, lessening the severity of, preventing, or delaying the onset of amyloid-related disorders, such as Alzheimer's disease and HIV associated neurocognitive impairment.</p>
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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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8-HYDROXYQUINOLINE DERIVATIVES AS DIAGNOSTIC AND THERAPEUTIC AGENTS (Fri, 17 Feb 2017)
The present application provides compounds useful in methods of treating neurological disorders such as Alzheimer's disease, and cancer such as prostate cancer. Also provided herein are radiolabeled compounds useful for imaging techniques, and techniques for diagnosis and monitoring of treatment of neurological disorders and cancer. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography or single- photon emission computed tomography. Methods for preparing radiolabeled compounds and methods for preparing unlabeled compounds are also provided.
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COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING NEURODEGENERATIVE DISORDERS (Fri, 17 Feb 2017)
Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.
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BACE1 INHIBITORS (Fri, 17 Feb 2017)
The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 17 Feb 2017)
A compound of Formula (I) is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula (I) as TD02 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula (I).
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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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Sulfonamide Derivatives And Pharmaceutical Applications Thereof (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">Provided herein are sulfonamide derivatives or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and use of such compounds or pharmaceutical compositions thereof for managing or treating 5-HT<sub>6 </sub>receptor-mediated diseases, especially in the manufacture of a medicament for managing or treating Alzheimer's disease.</p>
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Iminothiadiazepane dioxide compounds as BACE inhibitors, compositions, and their use (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain iminothiadiazepane dioxide compounds, including compounds Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.11mm" wi="60.54mm" file="US09745324-20170829-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>N</sup>, R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, ring A, R<sup>A</sup>, m, -L<sub>1</sub>-, and R<sup>L </sup>are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p>
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 10 Feb 2017)
The present invention provides, in part, compounds of Formula I and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 10 Feb 2017)
Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.
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BROAD SPECTRUM REACTIVATORS OF OPNA-INHIBITION OF HUMAN CHOLINESTERASES (Fri, 10 Feb 2017)
The present invention deals with novel compounds which are reactivators of human acetylcholinesterase, pharmaceutical compositions comprising said compounds, and their use in the treatment of a nervous and/or respiratory failure due to intoxication with at least one organophosphorous nerve agent such as warfare agents and pesticides. It also pertains to these compounds for use in the treatment of neurological diseases such as Alzheimer's disease.
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VINYL FLUORIDE CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 10 Feb 2017)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A7, and each of Ra, Rb, R1, R2, R3, R8 R9 and R10 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions.
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.98mm" wi="62.91mm" file="US20170029390A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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2-SUBSTITUTED-5-HYDROXY-4H-CHROMEN-4-ONES AS NOVEL LIGANDS FOR THE SEROTONIN RECEPTOR 2B (5-HT2B) (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">A family of compounds which function as selective ligands for the serotonin receptor 2B (5-HT<sub>2B</sub>) is identified. Some of the compounds are synthetic non-natural ligands which have a relatively strong interaction with 5-HT2B compared to naturally occurring compounds (some of which are identified for the first time herein as ligands for 5-HT<sub>2B</sub>). Because the compounds, both naturally occurring and synthetically produced, function as ligands for 5-HT<sub>2B </sub>they will have application in, for example, the treatment and/or prevention of nervous system disorders such as Alzheimer's disease.</p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.23mm" wi="69.85mm" file="US20170029417A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Nitrogen-containing heterocyclic compound (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.57mm" wi="53.76mm" file="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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Use of N-(4-isopropylphenyl)-5-amino-isoindoline (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to a novel use of N-(4-isopropylphenyl)-5-amino-isoindoline for diagnosing Alzheimer's disease and quantifying amyloid in the brain.</p>
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Feb 2017)
The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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2-amino-benzimidazole derivatives and their use as 5-lipoxygenase and/or prostaglandin e synthase inhibitors (Fri, 03 Feb 2017)
The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X<sp>1</sp> and X<sp>2</sp> are independently, at each occurrence, CR<sp>5</sp> or N; Y is C<sb>1</sb>-C<sb>6</sb> alkylene, wherein alkylene is optionally substituted with one to two C<sb>1</sb>-C<sb>3</sb> alkyl groups; R<sp>1</sp> is selected from the group consisting of hydrogen, halogen, C<sb>1</sb>-C<sb>6</sb> alkoxy, -NH<sb>2</sb>, -NHR<sp>6</sp>, -NR<sp>7</sp>R<sp>8</sp> and -NH-(R<sp>9</sp>)<sb>n</sb>-R<sp>10</sp>, n being 0 or 1; R<sp>2</sp> is selected from the group consisting of hydrogen, halogen, C<sb>1</sb>-C<sb>6</sb> alkyl, -NH<sb>2</sb>, -NHR<sp>6</sp>, - NR<sp>7</sp>R<sp>8</sp> and -NH-(R<sp>9</sp>)<sb>n</sb>-R<sp>10</sp>; R<sp>3</sp> is selected from the group consisting of hydrogen, hydroxyl, OR<sp>11</sp>, -NR<sp>7</sp>R<sp>8</sp>, C<sb>1</sb>-C<sb>6</sb> alkoxy, C<sb>1</sb>-C<sb>6</sb> alkyl, C<sb>3</sb>-C<sb>10</sb> cycloalkyl, C<sb>1</sb>-C<sb>3</sb> haloalkyl, -C(O)NHR<sp>11</sp>, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R<sp>a</sp> groups; and R<sp>4</sp> is selected from the group consisting of -NH<sb>2</sb>, -N(R<sp>12</sp>)(V)<sb>p</sb>R<sp>13</sp>, - NH(V)<sb>p</sb>-OR<sp>14</sp>, -NHC(O)R<sp>15</sp>, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
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COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia.</p>
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PRODRUG OF AN ICE INHIBITOR (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">This invention describes an ICE inhibitor prodrug (I) having good bioavailability.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.02mm" wi="73.74mm" file="US20170022249A1-20170126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.</p>
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HETEROCYCLIC COMPOUND AND USE THEREOF (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Provided is a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.35mm" wi="69.85mm" file="US20170022222A1-20170126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the specification, or a salt thereof, which has an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action. The compound of the present invention is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like.</p>
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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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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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Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, gamma-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1) (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">Novel forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-Dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1-H-pyrrole-1-heptanoic acid hemi calcium salt designated Form XX, Form XXI, Form XXII, Form XXIII, Form XXIV, Forms XXV, Form XXVI, Form XXVII, Form XXVIII, Form XXIX, and Form XXX characterized by their X-ray powder diffraction, solid state NMR, and/or Raman spectroscopy are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia (BPH) and Alzheimer's disease.</p>
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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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COMPOUNDS (Fri, 27 Jan 2017)
Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
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CRYSTAL FORMS OF TETRA-HYDRO-N, N-DIMETHYL-2, 2-DIPHENYL-3-FURANMETHANAMINE HYDROCHLORIDE, PROCESSES FOR MAKING SUCH FORMS, AND THEIR PHARMACEUTICAL COMPOSITIONS (Fri, 27 Jan 2017)
Polymorphic forms of tetrahydro-N,N-dimethyl-2,2-diphenyl-3- furanmethanamine hydrochloride (ANAVEX2-73) and a metabolite of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) are disclosed and characterized. Compositions and method for treatment of Alzheimer's disease that includes the polymorphic forms and metabolite of tetrahydro-N,N-dimethyl-2,2- diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73).
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METHODS AND COMPOSITIONS COMPRISING TAU OLIGOMERS (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught. Methods for producing and purifying these structures for the development of small molecule and immunotherapeutics as well as antibodies for biomarkers of neurodegenerative diseases are taught.</p>
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Antibodies Specific for Hyperphosphorylated Tau and Methods of Use Thereof (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to a novel class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396), as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and tauopathies.</p>
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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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ANTIBODIES SPECIFIC FOR HYPERPHOSPHORYLATED TAU AND METHODS OF USE THEREOF (Fri, 20 Jan 2017)
The present invention relates to a novel class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396), as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and tauopathies.
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NOVEL IMAGING COMPOUNDS (Fri, 20 Jan 2017)
The present invention relates to novel compounds that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.
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DIHYDROPYRIDOPYRROLE DERIVATIVES AS TAU-PET-LIGANDS (Thu, 19 Jan 2017)
The present invention relates to novel compounds of formula (I) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other Tauopathies using Positron Emission Tomography (PET) Imaging. Formula (I):
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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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Quinoline compounds (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to quinoline compounds as defined by Formula I below. Such quinoline compounds have been shown to inhibit the formation of amyloid deposits (e.g., amyloid oligomers, fibrils or plaques). Consequently, these compounds are suitable for treating a range of diseases and disorders in which amyloid deposits are implicated, such as type-2 diabetes and Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="63.42mm" file="US09822078-20171121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </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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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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Carbazole and Carboline Compounds for Use in the Diagnosis, Treatment, Alleviation or Prevention of Disorders Associated with Amyloid or Amyloid-Like Proteins (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds that can be employed in the diagnosis, treatment, alleviation or prevention of a group of disorders and abnormalities associated with amyloid proteins and amyloid-like proteins, such as Alzheimer's disease. Precursors for the preparation of the compounds according to the present invention are also provided.</p>
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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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MOLECULAR RE-ENGINEERING OF EXCITATION-INHIBITION BALANCE IN MEMORY CIRCUITS (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">Disclosed are memory-regulating agents and methods that target actin binding LIM protein family, member 3 (ABLIM3). Specifically, the disclosure provides methods of inhibiting Ablim3 using inhibitory nucleic acids that target the Ablim3 gene or mRNA to improve memory in subjects with memory dysfunction associated with Alzheimer's Disease (AD), normal aging, or posttraumatic stress disorder (PTSD). Further disclosed is a cell-based assay that can be used to screen for small molecule regulat ors of Ablim3 function.</p>
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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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Omegabalins, GABA derivatives of omega-3 polyunsaturated acids, their formulations and methods of use (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to omegabalins, which are GABA derivatives of omega-3 fatty acids, and their use in pharmaceutically-acceptable formulations for treating neuropathic pain, fibromyalgia, epilepsy, anxiety, depression, insomnia, Alzheimer's disease, and other neurological conditions.</p>
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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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TRIAZINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES (Thu, 29 Dec 2016)
Provided is a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and cancer including colorectal cancer. A compound represented by the formula [I] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the SPECIFICATION.
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Substituted pyrido[2,3-b]pyrazines as phosphodiesterase 2A inhibitors (Wed, 28 Dec 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a PDE2A selective inhibitory action, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like.</p> <p id="p-0002" num="0000">The present invention is a compound represented by the formula (1):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="57.74mm" file="US09527841-20161227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, or a salt thereof. </p>
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BIS-FURAN DERIVATIVES AS TRANSTHYRETIN (TTR) STABILIZERS AND AMYLOID INHIBITORS FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY (FAP) (Fri, 23 Dec 2016)
The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloid polyneuropathy (FAP), despite their lower molecular weight and lipophilicity. Moreover, ex vivo experiments with the strongest inhibitor in the series, conducted in human blood plasma from normal and FAP Val30Met-transthyretin carriers, disclose remarkable affinity and selectivity profiles. The promises and challenges facing further development of this compound are discussed under the light of increasing evidence implicating transthyretin stability as a key factor not only in transthyretin amyloidoses and several associated co-morbidities, but also in Alzheimer's disease.
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PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds (referred to herein as “PPDA compounds”) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.</p>
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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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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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Compounds targeting proteins, compositions, methods, and uses thereof (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.</p>
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Compounds (Fri, 16 Dec 2016)
The present invention relates to novel compounds that inhibit Lp-PLA<sb>2</sb> activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA<sb>2,</sb> for example atherosclerosis, Alzheimer's disease.
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Compounds (Fri, 16 Dec 2016)
The present invention relates to novel compounds that inhibit Lp-PLA<sb>2</sb> activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA<sb>2</sb>, for example Alzheimer's disease.
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Aromatic heterocyclic derivatives and pharmaceutical applications thereof (Fri, 16 Dec 2016)
Provided herein are aromatic heterocyclic derivatives or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof used for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and use of such compounds or pharmaceutical compositions thereof for managing or treating 5-HT<sb>6</sb> receptor-mediated diseases, especially in the manufacture of a medicament for managing or treating Alzheimer's disease.
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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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INHIBITORS OF COGNITIVE DECLINE (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimer's disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimer's disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention.</p>
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NEW COMPOUNDS HAVING A SELECTIVE PDE4D INHIBITING ACTIVITY (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">Compounds of formula (I), wherein Z=cyclopentyl. cyclopropylmethyl, —CH<sub>3</sub>; R′=—CH<sub>3</sub>, CHF<sub>2</sub>, X=formula (II) (III) (IV) (V) Y=—CO; —C═O(CH<sub>2</sub>), —CH(OH)—CH<sub>2</sub>, —CH<sub>2</sub>—C═O, —CH<sub>2</sub>—CH<sub>2</sub>—C═O; —CH<sub>2</sub>—CH(OH)—CH<sub>2</sub>, —CH<sub>2</sub>—CH(OCOR<sub>1</sub>)—CH<sub>2 </sub>NR<sub>2</sub>=—N(CH<sub>2</sub>—CH<sub>2</sub>OH)<sub>2</sub>, formula (VI) (VII) (VIII) (IX) (X) (XI) R<sub>1</sub>=optionally substituted C<sub>1</sub>-C<sub>8 </sub>alkyl, optionally substituted aryl; optionally substituted aralkyl, preferably C<sub>1</sub>-C<sub>3 </sub>alkyl, more preferably CH<sub>3</sub>; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof; these compounds have a PDE4D inhibiting activity and can be used as a medicament for treating dementia, in particular Alzheimer disease, and for improving memory.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="229.95mm" wi="72.22mm" file="US20160355489A1-20161208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="47.33mm" wi="49.19mm" file="US20160355489A1-20161208-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.</p>
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3-(6-CHLORO-3-OXO-3,4-DIHYDRO-(2H)-1,4-BENZOXAZIN-4-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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3-(5-CHLORO-2-OXO-2,3-DIHYDRO-1,3-BENZOTHIAZOL-3-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 02 Dec 2016)
The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.
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Dosing regimens for treating and/or preventing cerebral amyloidoses (Fri, 02 Dec 2016)
Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).
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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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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: R<sp>1</sp> is heteroaryl optionally 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 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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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: R<sp>1</sp> is heteroaryl optionally 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, 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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METHODS OF TREATING NEUROLOGICAL, METABOLIC, AND OTHER DISORDERS USING ENANTIOPURE DEUTERIUM-ENRICHED PIOGLITAZONE (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The invention provides enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating neurological disorders, cancer, respiratory disorders, metabolic disorders, and other disorders using enantiopure deuterium-enriched pioglitazone. A preferred aspect of the invention provides methods of treating Alzheimer's disease, non-small cell lung cancer, hepatocellular carcinoma, and chronic obstructive pulmonary disease using enantiopure deuterium-enriched pioglitazone.</p>
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FUSED IMIDAZOLE COMPOUNDS (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABA<sub>A </sub>α5) and act as GABA<sub>A </sub>α5 negative allosteric modulators (GABA<sub>A </sub>α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABA<sub>A </sub>α5 such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="69.85mm" file="US20160331757A1-20161117-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHOD OF DIAGNOSIS, PROGNOSTIC OR TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">Methods for the diagnosis and prognosis of neurodegenerative diseases, such as Alzheimer's disease, are described. Compositions and method for the treatment of neurodegenerative diseases are also described.</p>
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QUINOLINE DERIVATIVES FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER'S DISEASE (Fri, 18 Nov 2016)
A new class of quinoline compounds is useful for the detection and treatment of Alzheimer's disease and other neurodegenerative diseases such as amyloidoses and tauopathies. The compounds can be synthesized in radiolabeled form for use as imaging agents, which can be used for early detection of aggregates in the brain or other tissues prior to onset of symptoms, allowing early therapeutic intervention. The compounds are also useful for the prevention and treatment of such diseases.
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4H-PYRAN COMPOUNDS AS INSULIN-REGULATED AMINOPEPTIDASE (IRAP) INHIBITORS (Fri, 18 Nov 2016)
The present disclosure relates to 4H-pyran compounds of formula (I) and their use in therapy, to compositions and agents comprising said compounds, to methods of treatment using said compounds, and their use in the manufacture of medicaments. The disclosure further relates to said compounds and compositions thereof as inhibitors of IRAP and their use in the treatment or prevention of Alzheimer's disease and the treatment and prevention of memory and cognitive disorders.
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A CASEIN KINASE 1 DELTA INHIBITOR (Fri, 18 Nov 2016)
The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl) carbonyl] indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.
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PYRIDAZINE COMPOUNDS, COMPOSITIONS AND METHODS (Fri, 11 Nov 2016)
<p id="p-0001" num="0000">The invention relates to novel chemical compounds, compositions and methods of making and using the same. In particular, the invention provides pyridazine compounds and/or related heterocyclic derivatives, compositions comprising the same, and methods of making and using pyridazine compounds and/or related heterocyclic derivatives and compositions comprising the same, for modulation of cellular pathways (e.g., signal transduction pathways), for treatment or prevention of inflammatory diseases (e.g., Alzheimer's disease), for research, drug screening, and therapeutic applications.</p>
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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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Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles (Fri, 11 Nov 2016)
The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain <i>in vivo</i> to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.
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1H-pyrazolo[3,4-<i>b</i>]pyridines and therapeutic uses thereof (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">Provided herein are compounds according to Formulas (I) or (II) and pharmaceutically acceptable salts thereof, and compositions comprising the same, for use in various methods, including treating cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, osteoarthritis, idiopathic pulmonary fibrosis and neurological conditions/disorders/diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="93.30mm" wi="63.16mm" file="US09586977-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-(5-CHLORO-2-OXOBENZO[D]OXAZOL-3(2H)-YL) PROPANOIC ACID DERIVATIVES AS KMO INHIBITORS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">A compound of formula (I) or a salt thereof are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="57.40mm" file="US20160318884A1-20161103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, X and R<sup>3 </sup>are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.</p>
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URIDINE DIPHOSPHATE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISORDERS (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">This disclosure relates to uridine di phosphate (UDP) derivatives, compositions comprising therapeutically effective amounts of those UDP derivatives and methods of using those derivatives or compositions in treating disorders that are responsive to ligands, such as agonists, of P<sub>2</sub>Y<sub>6 </sub>receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease) and traumatic CNS injury, as well as pain.</p>
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4-(piperrazin-1-yl)-pyrrolidin-2-one compounds as monoacylglycerol lipase (MAGL) inhibitors (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention aims to provide a compound having an MAGL inhibitory action, and useful as a prophylactic or therapeutic agent for neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis and the like), anxiety disorder, pain (e.g., inflammatory pain, carcinomatous pain, nervous pain and the like), epilepsy and the like. The present invention relates to a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.19mm" wi="69.85mm" file="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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5-aryl-1-imino-1-oxo-[1,2,4]thiadiazines (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention provides a compound of formula I′ having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.28mm" wi="55.63mm" file="US09605006-20170328-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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P-GP RADIOTRACERS FOR IMAGING AS BIOMARKER INVOLVED IN ONSET OF NEURODEGENERATIVE DISEASES (Fri, 04 Nov 2016)
The invention includes a new class of radiolabeled compounds of formula I able to bind P-glycoprotein with high affinity and selectivity. The protein prevents accumulation in the brain of a wide range of drugs and, changes in P-gp expression and function, are also believed to occur in several neurological disorder, such as Alzheimer's disease (AD). Indeed, it is widely reported that decreased expression of P- gp and/or activity at the BBB level could cause accumulation of I3- amyloid plaques, the main hallmark of AD onset. 13-amyloid is a P-gp substrate, and these results support the importance of P-gp in the clearance of 13-amyloid peptide from brain parenchyma. For this reason, P-gp can be considered a useful biomarker for the early diagnosis of neurodegeneration. There is considerable interest in the development of P-gp PET radiotracers for imaging expression and function of P-gp. Formula I wherein the compound is labeled with an isotope selected from H, 11C 14C, 13N, 150 18F 19F, 75Br, 76Br, 79Br.
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 04 Nov 2016)
Provided in some embodiments are compounds herein. Also provided in some embodiments are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided in some embodiments are compositions comprising a compound herein, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a compound herein, optionally in combination with a supplemental agent.
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Cyclopropanamine compound and use thereof (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="69.85mm" file="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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ALPHA B-CRYSTALLIN FOR USE IN TREATING GLUTAMATE EXCITOTOXICITY OR TAUOPATHIES (Fri, 28 Oct 2016)
The present invention describes a compound for use in treating or preventing glutamate excitotoxicity and/or tauopathy in a subject, preferably a disorder selected from the group of epilepsy, spinal cord injury, stroke, traumatic brain injury, Alzheimer's disease, Pick's disease, amyotrophic lateral sclerosis, frontotemporal dementia, frontotemporal lobar degeneration, progressive supranuclear palsy, Parkinsonism linked to chromosome 17, cortical basal degeneration, hearing loss, and in alcoholism or alcohol withdrawal problems, wherein said compound comprises a small heat shock protein having an alpha-crystallin domain, and methods for treating or preventing glutamate excitotoxicity and/or tauopathy in a subject, using said compound.
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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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A prodrug of 1,1'-(1,6-dioxo-1,6-hexanediyl)bis-d-proline (Fri, 28 Oct 2016)
The present invention relates to the compound (2R,2'R)-bis(((((tetrahydro-2H-pyran- 4-yl)oxy)carbonyl)oxy)methyl) 1,1'-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.
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Imidazo isoindole derivative, preparation method therefor and medical use thereof (Fri, 28 Oct 2016)
The present invention relates to an imidazo isoindole derivative, a preparation method therefor and a medical use thereof. In particular, the present invention relates to the imidazo isoindole derivative as shown in the formula (I), a preparation method and pharmaceutical composition containing the derivative, and a use thereof for treating diseases with the pathological characteristic of IDO-mediated tryptophan metabolic pathways. The diseases comprise cancers, Alzheimer's disease, autoimmune diseases, depression, anxiety disorders, cataracts, psychological disorders and AIDS, wherein the substituents in the formula (I) are the same as those defined in the description.
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METHOD FOR PREPARING THE ANHYDROUS CRYSTALLINE FORM OF ISONIAZID-DERIVED HYDRAZONE, THUS PRODUCED CRYSTALLINE POLYMORPH OF THE ANHYDROUS FORM, USE THEREOF FOR THE TREATMENT OF ALZHEIMER'S DISEASE, PARKINSONISM AND OTHER NEURODEGENERATIVE DISORDERS, AND PHARMACEUTICAL COMPOSITION (Thu, 27 Oct 2016)
The present invention relates to the method for preparing the anhydrous crystalline form of isoniazid-derived hydrazone (8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone), to the thus produced polymorph and to the use thereof for the treatment of Alzheimer's disease and parkinsonism, inter alia, and to a pharmaceutical composition.
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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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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 TO ASSESS THE CAPACITY OF HDL TO SUPPORT REVERSE CHOLESTEROL TRANSPORT (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">The invention provides compositions and methods for assessing the capacity of high density lipoprotein (HDL) to support reverse cholesterol transport in blood by measuring exchange if HDL-specific spin-labeled lipoprotein probes and electron paramagnetic spectroscopy. The invention also provides methods to identify individuals at risk for cardiovascular disease, to monitor the treatment of cardiovascular disease and in the development of therapies to treat cardiovascular disease. The invention also provides methods to identify individuals at risk for Alzheimer's disease, to monitor the treatment of Alzheimer's disease and in the development of therapies to treat Alzheimer's disease.</p>
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Gamma secretase modulators (Fri, 21 Oct 2016)
<p id="p-0001" num="0000">Disclosed herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the compound of Formula (I) and use of the compound in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="63.08mm" file="US09598437-20170321-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 21 Oct 2016)
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
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TREATMENT OF ALZHEIMER'S DISEASE, LOSS OF COGNITION, MEMORY LOSS, AND DEMENTIA WITH SEX STEROID PRECURSORS IN COMBINATION WITH SELECTIVE ESTROGEN RECEPTOR MODULATORS (Fri, 21 Oct 2016)
Novel methods for reduction or elimination of the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly benzopyran compounds. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.
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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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INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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SPIROCYCLIC COMPOUNDS CONTAINING SPIRO[INDOLYL-3,1'-PYRROLO[3,4-C]PYRROLE] CORE AND SULPHUR-CONTAINING AMINO ACID RESIDUES (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to spirocyclic compounds on the basis of 2-oxindole derivatives containing a spiro[indolyl-3,1′-pyrrolo[3,4-c]-pyrrole] core and biogenic sulphur-containing amino acid residues, which display a glucocorticoid-mimicking action by influencing 11β-HSD1 enzyme cortisone->cortisol conversion, or by inhibiting GRs- or GITR- or mineralocorticoid receptors, or other targets, but do not interfere with steroidal haemostasis in HPA; and compositions containing same and their use for therapy as part of undifferentiated stroke therapy (in the absence of final verification of the stroke subtype) at various stages of acute ischemic stroke (AIS), during the period of recovery from stroke and craniocerebral trauma, in patients with chronic cerebrovascular pathology (against a background of diabetes), in combinational therapy for Alzheimer's disease and encephalopathy of various origin (discirculatory, alcoholic, infectious-toxic), and diabetes, combinational therapy for retinal degenerative eye diseases, as part of combinational therapy for metabolic syndrome (obesity, in patients suffering from Cushing's syndrome, Reaven metabolic syndrome (also known as syndrome X or insulin resistance syndrome) and other diseases where GCs hormones play a key role.</p>
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Process for large scale production of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">A process suitable for adoption to large scale manufacture of 1-[(2-bromophenyl-sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate, which is a selective 5-HT<sub>6 </sub>receptor antagonist intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.</p>
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S1P3 ANTAGONISTS (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to antagonists of the S1P3 receptor formula (A) as herein described and pharmaceutical compositions thereof. The compounds of formula (A) are useful in the preparation of a medicament, in particular for the treatment of Alzheimer's disease.</p>
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IMMUNOLOGICAL METHODS AND COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to immunogenic compositions and peptides comprising residues 4-10 (FRHDSGY) of the amyloid peptide Abeta<sub>42</sub>. The invention further relates to antibodies that bind to the Abeta<sub>(4-10) </sub>antigenic determinant. The invention provides methods for treating Alzheimer's disease and for reducing the amyloid load in Alzheimers patients. The invention also relates to methods for designing small molecule inhibitors of amyloid deposition.</p>
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PROCESS FOR LARGE SCALE PRODUCTION OF 1-[(2-BROMOPHENYL)SULFONYL]-5-METHOXY-3-[(4-METHYL-1-PIPERAZINYL)METHYL]-1H-INDOLE DIMESYLATE MONOHYDRATE (Thu, 13 Oct 2016)
A process suitable for adoption to large scale manufacture of 1-[(2- bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl- 1-piperazinyl)methyl]-1H-indole dimesylate monohydrate, which is a selective 5-HT<sb>6</sb> receptor antagonist intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.
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Hybrid compounds of curcumin and melatonin as neuroprotectants for neurodegenerative disorders (Fri, 07 Oct 2016)
<p id="p-0001" num="0000">Hybrid compounds of curcumin and melatonin as neuroprotectants are provided. The hybrid compounds are useful for the treatment and/or prevention of Alzheimer's disease (AD), as well as other neurodegenerative diseases. The hybrid compounds exhibited superior and potent neuroprotection in an AD model.</p>
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METHODS AND MATERIALS FOR REDUCING AMYLOID BETA LEVELS WITHIN A MAMMAL (Fri, 07 Oct 2016)
This document provides methods and materials for reducing amyloid beta levels within a mammal (e.g. a mammal having Alzheimer's disease). For example, this document provides methods for using compositions containing a potato polysaccharide preparation to reduce one or more symptoms of Alzheimer's disease. In some cases, a composition containing a potato polysaccharide preparation provided herein can be used to increase binding, sequestration, and/or degradation of CNS-derived amyloid beta polypeptides, thereby inhibiting the formation of neurofibrillary plaques.
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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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Methods and materials for reducing amyloid beta levels within a mammal (Fri, 07 Oct 2016)
This document provides methods and materials for reducing amyloid beta levels within a mammal (e.g. a mammal having Alzheimer's disease). For example, this document provides methods for using compositions containing a potato polysaccharide preparation to reduce one or more symptoms of Alzheimer's disease. In some cases, a composition containing a potato polysaccharide preparation provided herein can be used to increase binding, sequestration, and/or degradation of CNS-derived amyloid beta polypeptides, thereby inhibiting the formation of neurofibrillary plaques.
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Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.40mm" wi="56.47mm" file="US09611261-20170404-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein variables A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, A<sup>8</sup>, each of R<sup>a</sup>, R<sup>b</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>7 </sup>of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention. </p>
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DISUBSTITUTED PIPERIDINE DERIVATIVES AS BUTYRYLCHOLINESTERASE INHIBITORS FOR USE IN THE TREATMENT OF ALZHEIMER (Fri, 30 Sep 2016)
This invention relates to new inhibitors of butyrylcholinesterase with general formulas I and II, where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the treatment of Alzheimer's disease and other forms of dementia.
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METHOD OF DIAGNOSIS OR TREATMENT OF NEUROLOGICAL DISORDERS WITH P75ECD AND/OR P75 (Fri, 30 Sep 2016)
A method of treating and/or preventing neurological conditions, comprising administering to a subject in need thereof a therapeutically effective amount of a p75 extracellular domain (p75ECD) or a functional fragment, variant, analogue or derivative thereof. Also provided is a method of diagnosing and/or prognosing Alzheimer's disease (AD) in a test subject comprising comparing the concentration of p75ECD and/or p75FL and/or the ratio of p75ECD: p75FL in a biological sample of the test subject to the concentration of p75ECD and/or p75FL and/or the ratio of p75ECD: p75FL in a comparable biological sample obtained from a non-demented control subject(s).
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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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SPIROCYCLIC DIHYDRO-THIAZINE AND DIHYDRO-OXAZINE BACE INHIBITORS, AND COMPOSITIONS AND USES THEREOF (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">Compounds are provided having a structure according to Formula (I): wherein A<sub>1</sub>, A<sub>2</sub>, A<sub>3</sub>, Y, R<sub>1</sub>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, m, n and p are defined herein. Further provided are pharmaceutical compositions including the compounds provided and methods of making and using the compounds and compositions as provided, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.</p>
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HUMANIZED ANTIBODY (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease.</p>
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Tau imaging probe (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">An object of the present invention is to provide a probe for imaging a β-sheet structure protein which can be used for the diagnosis of conformational diseases, particularly disease (tauopathy) having a cardinal symptom such as intracerebral accumulation of tau protein, for example, Alzheimer's disease. Another object of the present invention is to provide a compound which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or non-recognized toxicity.</p> <p id="p-0002" num="0000">According to the present invention, the above problems are solved by providing a compound of a formula I (wherein A, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>a </sup>and R<sup>b </sup>are as defined in the present description) or a pharmaceutically acceptable salt or solvate thereof.</p>
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also 10 relates to a process for manufacturing compounds of Formula I.
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ADENOSINE THIOPHOSPHATE DERIVATIVES AND USES THEREOF (Fri, 23 Sep 2016)
Novel adenosine 5'-thiophosphate derivatives, represented by Formulae (I) or (I*), and salts thereof, represented by Formulae (Ia) and (I*a), as defined in the specification, and uses thereof as antioxidants and/or P2Y1-R agonists, and/or in the treatment of medical conditions associated with oxidative stress and/or neurodegeneration, and in the treatment of Alzheimer's Disease in particular, are disclosed.
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 23 Sep 2016)
Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu2), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.
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Chromene and 1,1 a,2,7b-tetrahydrocyclopropa[c]chromene pyridopyrazinediones as gamma-secretase modulators (Fri, 23 Sep 2016)
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I), wherein X, R<sp>1</sp>, R<sp>2a</sp>, R<sp>2b</sp>, R4<sp>a</sp>, R<sp>4b</sp>, R<sp>5a</sp>, R<sp>5b</sp>, R<sp>6</sp>, R<sp>7,</sp> y and z are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed. These compounds are γ-secretase modulators, useful for the treatment of neurodegenerative and/ or neurological disorders such as Alzheimer's disease and Down's syndrome.
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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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ALZHEIMER'S DISEASE ASSAY IN A LIVING PATIENT (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">An assay for Alzheimer's disease pathology (AD) in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, TLR4-FLNA and/or α7nAChR-Aβ<sub>42 </sub>complex present as a protein-protein complex in a sample is determined and compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is determined and compared to an amount determined in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four of the six pharmacophores of FIGS. <b>7</b>-<b>12</b>. An amount of protein or protein complex determined in the presence of the medicament less than the first determined amount indicates a favorable treatment prognosis.</p>
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C6-spiro iminothiadiazine dioxides as BACE inhibitors, compositions, and their use (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): (structurally represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds, wherein R1, R2, R3, X, Y, s, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="57.15mm" file="US09580396-20170228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLIC COMPOUND (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">The problem of the present invention is to provide a compound having a PDE2A inhibitory action, and useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="69.93mm" file="US20160264536A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the DESCRIPTION, or a salt thereof.</p>
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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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CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula;</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="66.80mm" wi="76.03mm" file="US20160263257A1-20160915-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X is OH, C<sub>1</sub>-C<sub>6 </sub>alkoxyl; Y and Z are independently selected from a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxyl, halogen, mi-substituted or C<sub>1</sub>-C<sub>6 </sub>substituted amine, <sup>18</sup>F, <sup>19</sup>F, or H; and n is 1, 2, or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H and X is OH.</p>
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Phosphonate derivatives and methods of use thereof in the treatment of Alzheimer's disease (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">Benzothiazole phosphonate analogs and methods of using the same to inhibit the activity of Amyloid Binding Alcohol Dehydrogenase and in the amelioration or treatment of Alzheimer's disease are provided.</p>
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SYNTHESIS AND UTILITY OF NEW CAPGROUP LARGAZOLE ANALOGS (Fri, 16 Sep 2016)
Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.
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METHODS FOR TREATING PROTEINOPATHIES (Fri, 16 Sep 2016)
This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.
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Synthesis and utility of new capgroup largazole analogs (Fri, 16 Sep 2016)
Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.
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Methods for treating proteinopathies (Fri, 16 Sep 2016)
This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.
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THERAPEUTIC COMPOUNDS (Sat, 10 Sep 2016)
The invention provides compounds formula (I) and salts thereof: wherein R1-R4 have any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, inflammation, hyperresponsiveness, allergic conditions, asthma, and psychotic disorders such as schizophrenia. The compounds are also useful to lower IL-4, IL-5, or IL-15 levels in an animal.
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6-substituted estradiol derivatives for the treatment of Alzheimer's Disease (Fri, 09 Sep 2016)
Disclosed is a method of treating Alzheimer's Disease with 6-substituted estradiol compounds of the formula. The methods can be used to treat a variety of diseases related to the up-regulation of lipoprotein lipase or apolipoprotein C2.
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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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Protective Effects of Oil Palm Composition on Alzheimer's Disease (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Present invention discloses an oil palm composition for use in prevention or treatment of Alzheimer's disease. The composition is useful in impeding formation of neurotoxic peptide. Present invention can be used in preparation of a medicament in a therapeutic effective amount for prevention or treatment of Alzheimer's disease and diseases related thereto.</p>
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CELLS EXPRESSING APOLIPOPROTEIN E AND USES THEREOF (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE-induced toxicity.</p>
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AROMATIC HETEROCYCLIC COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">Provided herein are novel aromatic heterocyclic compounds or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and methods for using such compounds or pharmaceutical compositions thereof to treat Alzheimer's disease.</p>
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3,3-disubstituted-(8-aza-bicyclo[3.2.1]OCT-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanones as inhibitors of 11 (β)-HSD1 (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.62mm" wi="57.23mm" file="US09834549-20171205-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS (Fri, 02 Sep 2016)
The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound- 1, or a pharmaceutically acceptable salt thereof.
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COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION (Fri, 02 Sep 2016)
The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation / retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.
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Compositions and methods for treating retinal degradation (Fri, 02 Sep 2016)
The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation / retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.
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HETEROCYCLIC COMPOUND (Thu, 01 Sep 2016)
The problem of the present invention is to provide a compound having a PDE2A inhibitory action, and useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.
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TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound-1, or a pharmaceutically acceptable salt thereof.</p>
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PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING DEGENERATIVE BRAIN DISEASE COMPRISING MULTI-TARGETING COMPOUNDS (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">A pharmaceutical composition for treating or preventing a degenerative brain disease, the pharmaceutical composition including, as an active component, a multi-targeting compound for further improving treatment efficiency of a degenerative brain disease such as Alzheimer's disease is disclosed. The pharmaceutical composition includes a compound represented by Formula 1 or 2, wherein the compound of Formula 1 or 2 induces a gathering of amyloid-peptides in a manner of toxicity-free aggregation under conditions both in the presence and absence of metals such as copper and zinc, and also reacts with multiple targets of Alzheimer's diseases at once to inhibit toxicity thereof, the multiple targets including amyloid-peptide, metal-amyloid-peptide, a metal, and an activated oxidizing species. The pharmaceutical composition including the compound of Formula 1 or 2 may be utilized as a therapeutic agent or a health food in regard to a brain disease, including Alzheimer's disease.</p>
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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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Imaging beta-amyloid peptides aggregation (Fri, 26 Aug 2016)
<p id="p-0001" num="0000">The present invention is in the field of pharmaceuticals and chemical industries. In particular, one aspect of the present invention relates to methods for labeling, imaging and detecting the beta-amyloid (Aβ) peptides, oligomers, and fibrils in vitro and in vivo via magnetic resonance and florescence imaging by using modified carbazole-based fluorophores. A further aspect of the present invention relates to a method of reducing and preventing aggregation of beta-amyloid peptides for Alzheimer's disease (AD) as well as of treating and/or preventing Alzheimer's disease by using the modified carbazole-based fluorophore. The modified carbazole-based fluorophore according to an embodiment of the present invention is prepared by conjugating a carbazole-based fluorophore with magnetic nanoparticles to form a conjugate which is permeable to blood brain barrier of a subject being introduced therewith.</p>
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Compounds and compositions for the detection and treatment of Alzheimer's disease and related disorders (Fri, 26 Aug 2016)
One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.
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1H-PYRAZOLO[3,4-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 26 Aug 2016)
Provided herein are compounds according to Formulas (I) or (II) and pharmaceutically acceptable salts thereof, and compositions comprising the same, for use in various methods including treating cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, osteoarthritis, idiopathic pulmonary fibrosis and neurological conditions/disorders/diseases.
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Methods of treating Alzheimer's Disease (Fri, 26 Aug 2016)
Methods of treating Alzheimer's Disease (AD) in patients suffering from mild to moderate AD, including ApoE4 positive patients and patients suffering from mild AD are provided. Also provided are methods of selecting or identifying patients for treatment with an anti-Abeta antibody. Methods include the use of prognostic and/or predictive biomarkers.
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Histamine-3 Receptor Antagonists (Fri, 19 Aug 2016)
<p id="p-0001" num="0000">The invention is directed to a compound of formula I, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I; and a method of treatment of a disorder or condition selected from the list consisting of acute myocardial infarction; memory processes disorders; dementia; cognition disorders such as Alzheimer's disease; attention deficit disorder (ADD); attention-deficit hyperactivity disorder (ADHD); cancers such as cutaneous carcinoma, medullary thyroid carcinoma and melanoma; Meniere's disease; gastrointestinal disorders; inflammation; migraine; motion sickness; obesity; pain; septic shock; respiratory disorders (including allergic rhinitis, nasal congestion and allergic congestion) in a mammal, including a human, that may be effected by administering to said mammal a pharmacologically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.</p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 19 Aug 2016)
Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu3), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.
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OLIGOMER-SPECIFIC AMYLOID BETA EPITOPE AND ANTIBODIES (Thu, 18 Aug 2016)
An isolated antibody that specifically binds to a cyclic peptide comprising the conformational epitope which has at least the amino acid sequences GSNK or SNKG, wherein the K (lysine) is solvent-exposed and wherein the antibody can specifically bind to amyloid beta is described. Methods of treating and preventing Alzheimer's disease, as well as methods to produce the antibody, are also described.
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Aryl methyl benzoquinazolinone M1 receptor positive allosteric modulators (Fri, 12 Aug 2016)
<p id="p-0001" num="0000">The present invention is directed to benzoquinazilinone compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.62mm" wi="36.07mm" file="US09708273-20170718-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor. </p>
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Oligomer-specific amyloid beta epitope and antibodies (Fri, 12 Aug 2016)
A novel constrained peptide epitope derived from AP, related antibody compositions and methods of use. An isolated antibody that specifically binds to a cyclic peptide comprising the conformational epitope corresponding to a solvent-exposed, antibody accessible knuckle region of oligomeric As is described. An antigenic peptide comprising an epitope having a constrained cyclic configuration, corresponding to a solvent-exposed, antibody accessible knuckle region of oligomeric A is also described. Methods of treating, preventing, and diagnosing Alzheimer's disease are also described.
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2-amino-3, 5, 5-trifluoro-3, 4, 5, 6-tetrahydropyridines as BACE1 inhibitors for treatment of Alzheimer's disease (Fri, 12 Aug 2016)
The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Αβ deposits is beneficial such as Alzheimer's disease.
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Methods of treating Alzheimer's Disease (Fri, 12 Aug 2016)
Methods of treating Alzheimer's Disease (AD) in patients suffering from mild to moderate AD, including ApoE4 positive patients and patients suffering from mild AD are provided.
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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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6-CYCLOALKYL-1, 5-DIHYDRO-PYRAZOLO [3, 4-D]PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A INHIBITORS (Thu, 11 Aug 2016)
Novel 6-Cycloalkyl-pyrazolopyrimidinones according to formula (I) with PDE9 inhibiting properties, wherein R 1 is a 5 or 6 membered aromatic heteroaryl-group, R 2 is an optional substituent, D is optionally substituted cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl or 2-, 3- or 4-pyridyl, m= 1 or 2 and n is 0, 1 or 2. The new compounds can be used as medicaments, in particular for the treatment of conditions concerning deficits in perception, concentration, learning or memory. Such conditions may be associated with Alzheimer's disease, schizophrenia and other diseases. The new compounds can be used in the treatment of cognitive impairment associated with such diseases.
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Indole derivatives and process for their preparation (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">Substituted indole derivatives of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.59mm" wi="60.45mm" file="US09629824-20170425-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein the radicals have e.g. the following meaning: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">R<sup>1 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl, R<sup>2 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl or cycloC<sub>3-12</sub>-alkyl;</li> <li id="ul0001-0002" num="0000">R<sup>3 </sup>is —OR</li> <li id="ul0001-0003" num="0000">R<sup>4 </sup>is hydrogen or halogen,</li> <li id="ul0001-0004" num="0000">R<sup>5 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl</li> <li id="ul0001-0005" num="0000">R<sup>6 </sup>is hydrogen, —C<sub>1-6</sub>-alkyl</li> <li id="ul0001-0006" num="0000">R is hydrogen or —C<sub>1-6</sub>-alkyl;</li> <li id="ul0001-0007" num="0000">X is a group —C(O)CH<sub>2</sub>— or —CH═CH—;</li> <li id="ul0001-0008" num="0000">R<sup>7 </sup>is hydrogen <br/> are potent inhibitors of Abeta peptide polymerization and can be used for the treatment of e.g. Alzheimers disease or ocular disorders. </li> </ul> </p>
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C5-spiro iminothiazine dioxides as BACE inhibitors, compositions, and their use (Fri, 05 Aug 2016)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein R<sup>L</sup>, X, Y, R<sup>1A</sup>, R<sup>1B</sup>, R2, R3, m, and RA are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="59.86mm" file="US09725468-20170808-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu<sub>2</sub>), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.</p>
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HETEROCYCLIC MOLECULES FOR BIOMEDICAL IMAGING AND THERAPEUTIC APPLICATIONS (Fri, 29 Jul 2016)
<p id="p-0001" num="0000">Probes which target diffuse and fibrillar forms of amyloid beta (Aβ) are described. These probes demonstrate high initial brain penetration and facile clearance from non-targeted regions. The agents can be used to image amyloid quantitatively for monitoring efficacy of Aβ-modifying therapeutics and assist in premortem diagnosis of Alzheimer's disease (AD). Disclosed probes can bind Aβ aggregates of preformed Aβ<sub>1-42 </sub>fibrils in vitro and can be used to image fibrillar and diffuse plaques ex vivo in brain sections. Disclosed probes can be used to determine Aβ burden in early stages of AD. These probes can be used for multimodality imaging of Aβ. F-AI-187(1 μM) can detect Aβ plaques in brain sections of APP/PS1 mice. F-AI-187(10 μM) can detect Aβ plaques in the frontal lobe in a brain section of a patient with confirmed AD. Some probes can be used for fluorescence imaging of plaque.</p>
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IMINOTHIADIAZINE DIOXIDES BEARING AN AMINE-LINKED SUBSTITUENT AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 29 Jul 2016)
In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, R2, ring A, RA, m, ring B, RB, and n are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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HUMANIZED ANTIBODY AGAINST AMYLOID BETA (Fri, 29 Jul 2016)
The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease.
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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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Methods of synthesizing γ-aapeptides, γ-aapeptide building blocks, γ-aapeptide libraries, and γ-aapeptide inhibitors of Aβ<sub>40 </sub>aggregates (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">Embodiments of the present disclosure provide for γ-AApeptides, γ-AApeptide building blocks, methods of making γ-AApeptides and libraries of γ-AApeptides, methods of screening the γ-AApeptide libraries for desired peptidomimetic activity, and the like. The present disclosure also provides for γ-AApeptides that are inhibitors of Aβ peptide aggregation, methods of inhibiting and disassembling Aβ peptide aggregation, methods of inhibiting the toxicity of Aβ aggregates towards N2a neuroblasotma cells, as well as methods and compounds for treating Alzheimer's disease.</p>
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Neuroprotective polyphenol analogs (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzheimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.</p>
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