Alzheimer's disease

SMALL MOLECULE INHIBITORS OF NEUTRAL SPHINGOMYELINASE 2 (nSMase2) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 13 Jul 2018)
Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.
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6-AMINO-5-FLUORO-5-(FLUOROMETHYL)-2,3,4,5-TETRAHYDROPYRIDIN-2-YL-PHENYL-5-(METHOXY-D3)-PYRAZINE-2-CARBOXAMIDES AND FLUORINATED DERIVATIVES THEREOF AS BACE1 INHIBITORS (Fri, 29 Jun 2018)
The invention provides amidine compounds of Formula (I) for the treatment of neurodegenerative or cognitive diseases, including Alzheimer's Disease.
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THIENOPYRROLE DERIVATIVES FOR USE IN TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 29 Jun 2018)
The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CKla, GSPTl, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.
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RADIOISOTOPE FLUORINE-18 SUBSTITUTED THIAMINE, SYNTHESIS METHOD THEREFOR, AND APPLICATIONS THEREOF (Thu, 28 Jun 2018)
The present invention discloses a radioisotope 18 F substituted thiamine, synthesis method, and use thereof in small animal PET/CT imaging. The radioisotope 18 F substituted thiamine has a structure of The synthesis method comprises radiochemical synthesis by using existing precursors. In the present invention, the hydroxyl in the hydroxyethyl on the thiazole cycle of thiamine is replaced by radioisotope 18 F, to prepare a PET tracer. The radioisotope 18 F substituted thiamine of the present invention successfully enters the brains of various strains of mice, and the uptake in the brains of thiamine-deficient mice is obviously greater than that in normal control. The present invention is useful in the preparation of a brain imaging tracer for clinical trials of Alzheimer's disease and tumors.
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HYDROXYTRIAZINE COMPOUND AND MEDICAL USE THEREOF (Thu, 28 Jun 2018)
The present invention provides a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and/or cancer including colorectal cancer. The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.
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OXAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (insert Formula I structure) wherein variables W, X, Y, R2, R2', R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to beta amyloid (Aβ) plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
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THIAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (see Formula I structure) wherein variables R1, R1', R2, R2', R3, R4, R5, R6, R7, and b of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
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CYCLOPROPYL FUSED THIAZINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I) wherein variables A, R1, R2, R2', R3, R4, and R5 of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
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1,4-THIAZINE DIOXIDE AND 1,2,4-THIADIAZINE DIOXIDE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND METHODS OF USE (Fri, 22 Jun 2018)
The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, X, R2, R2', R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
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BICYCLIC OGA INHIBITOR COMPOUNDS (Fri, 22 Jun 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.
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MONOCYCLIC OGA INHIBITOR COMPOUNDS (Fri, 22 Jun 2018)
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.
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3-(BENZOIMIDAZOL-2-YL)-INDAZOLE INHIBITORS OF THE WNT SIGNALING PATHWAY AND THERAPEUTIC USES THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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2,3-DIHYDRO-4H-1,3-BENZOXAZIN-4-ONE DERIVATIVES AS MODULATORS OF CHOLINERGIC MUSCARINIC M1 RECEPTOR (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof: wherein each symbol is as defined in the attached DESCRIPTION.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.62mm" wi="53.09mm" file="US20180162850A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CYCLOPROPANAMINE COMPOUND AND USE THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="69.85mm" file="US20180162853A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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HETEROCYCLIC COMPOUND AND USE THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Provided is a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.94mm" wi="69.85mm" file="US20180162875A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the specification, or a salt thereof, which has an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action. The compound of the present invention is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like.</p>
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BICYCLO[1.1.1]PENTANE INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 15 Jun 2018)
Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy -induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).
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Indazole inhibitors of the WNT signal pathway and therapeutic uses thereof (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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Amantadine nitrate compounds with neural protective effect, and preparation and medical use thereof (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to amantadine nitrate compounds having neural protective effect, and preparation method and medical use thereof. The compounds have the structure of the general formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.38mm" wi="51.31mm" file="US20180148404A1-20180531-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds have multifunctional mechanisms, including inhibiting NMDA receptors, releasing NO, inhibiting calcium influxes, and having protective effects on cells particularly neurocytes. The compounds can be used in the preparation of medicaments having a cellular protective effect, for prevention or treatment of the diseases related to such as NMDA receptors and elevation of calcium anions in cells, including the diseases related to neurodegeneration such as Alzheimer's disease, Parkinson's disease, cerebral paralysis and glaucoma, and the diseases related to cardio-cerebral-vascular system such as Parkinson's syndrome combined with cerebral arteriosclerosis, as well as respiratory tract infections caused by influenza virus.</p>
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Quinoline Derivatives for Diagnosis and Treatment of Alzheimer's Disease (Fri, 25 May 2018)
<p id="p-0001" num="0000">A new class of quinoline compounds is useful for the detection and treatment of Alzheimer's disease and other neurodegenerative diseases such as amyloidoses and tauopathies. The compounds can be synthesized in radiolabeled form for use as imaging agents, which can be used for early detection of aggregates in the brain or other tissues prior to onset of symptoms, allowing early therapeutic intervention. The compounds are also useful for the prevention and treatment of such diseases.</p>
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Compositions, Methods and Kits for Detection of Genetic Variants for Alzheimer's Disease (Fri, 25 May 2018)
<p id="p-0001" num="0000">Provided herein are methods, kits, and devices related to genetic variations of neurological disorders. For example, methods, kits, and devices for using such genetic variations to assess susceptibility of developing Alzheimer's disease.</p>
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Metal Delivery Agents and Therapeutic Uses of the Same (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention relates to metal complexes, processes for their preparation and their use as pharmaceutical or veterinary agents, in particular for the treatment of conditions in which metal delivery can prevent, alleviate or ameliorate the condition. There are a number of clinical conditions which are caused by or associated with abnormal levels of metals (typically low metal levels). Conditions in of this type include cancer and conditions characterised by or associated with oxidative damage, more specifically neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease or Huntington's disease. The invention also relates to ligands useful in the preparation of metal complexes of this type.</p>
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Therapeutic compounds (Fri, 25 May 2018)
<p id="p-0001" num="0000">The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.</p>
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2-SUBSTITUTED AMINO-NAPHTH[1,2-D]IMIDAZOL-5-ONE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS (Fri, 25 May 2018)
Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.
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NOVEL PYRAZOLE DERIVATIVE (Thu, 24 May 2018)
Provided is a novel therapeutic means for Alzheimer's disease. In particular, provided is a compound represented by the following general formula (I): [wherein Ar 1 represents 2-methoxy-4-(2-pyridylmethoxy)phenyl etc. and Ar 2 represents a 1H-indol-6-yl group etc.] or a salt thereof.
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 18 May 2018)
Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.
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PHENOXYTRIAZOLES (Fri, 18 May 2018)
The present invention relates to a compound of formula I, HetAr is a five or six membered heteroaryl group, selected from wherein R1 is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen, and may be the same or different, if two R1 occur; R2 is lower alkyl or a mono- or polydeutered derivative thereof, lower alkyl substituted by halogen or lower alkoxy, lower alkenyl unsubstituted or substituted by halogen, cycloalkyl or CH2-cycloalkyl unsubstituted or substituted by halogen, heterocycloalkyl or CH2-heterocycloalkyl unsubstituted or substituted by lower alkyl; R3 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or S(0)2-lower alkyl; n is 1, 2 or 3; if n is >1, then R3 may be the same or different; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or an optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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P2X7 MODULATORS (Thu, 17 May 2018)
The present invention is directed to a compound of Formula (I) or (la). The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (la) and methods comprising administering of compounds of Formula (I) or (la) for treating rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuroimmune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomemlonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, chlamydia, neuroblastoma, Tuberculosis, and migraine.
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BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Thu, 17 May 2018)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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4,4A,5,7-TETRAHYDRO-3H-FURO[3,4-B]PYRIDINYL COMPOUNDS (Sat, 12 May 2018)
The present invention relates to 4,4a,5,7-tetrahydro-3H-furo[3,4-b]pyridinyl compound inhibitors of beta-site APP-cleaving enzyme having the structure shown in Formula (I) wherein the radicals are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-site APP- cleaving enzyme is involved, such as Alzheimer's disease (AD), mild cognitive impairment, preclinical Alzheimer's disease, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, and dementia associated with beta-amyloid.
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COMPOSITIONS TARGETING 3-REPEAT TAU FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS, AND METHODS FOR MAKING AND USING THEM (Sat, 12 May 2018)
In alternative embodiments, provided are compositions such as antibodies, e.g., single chain antibodies, that target 3-repeat (3R) Tau for the treatment of neurodegenerative disorders and taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation, and methods for making and using them. In alternative embodiments, provided are brain-penetrating antibodies that specifically recognize 3R Tau, and methods of using them to treat, ameliorate, prevent or decrease the symptoms of neurodegenerative disorders including taupathies such as Alzheimer's Disease (AD), Pick's Disease (PiD) and Fronto-temporal lobar degeneration (FTLD), or any disorder or condition associated with a 3R Tau accumulation. Provided are methods for diagnosing a neurodegenerative disorder or a taupathy or any disorder or condition associated with a 3R Tau accumulation.
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SUBSTITUTED 6-MEMBERED ARYL OR HETEROARYL ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Sat, 12 May 2018)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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SUBSTITUTED BICYCLIC HETEROARYL ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Sat, 12 May 2018)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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COMPOUNDS FOR TREATMENT OF NEURODEGENERATIVE DISEASES (Sat, 12 May 2018)
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that can metabolize under physiological conditions to ornithine. The pH and plasma stability of compounds of formula (II) is also described. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
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Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions (Fri, 11 May 2018)
<p id="p-0001" num="0000">The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products.</p>
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Pro-Neurogenic Compounds (Fri, 11 May 2018)
<p id="p-0001" num="0000">This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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5-SUBSTITUTED INDAZOLE-3-CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, fibrotic disorders, cartilage (chondral) defects, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, and neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.</p>
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COMPOUNDS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.29mm" wi="59.86mm" file="US20180127405A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl optionally substituted by methyl, ethyl, halo or =0; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl. <br/> and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure. </li> </ul> </li> </ul> </p>
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COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 04 May 2018)
<p id="p-0001" num="0000">Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.25mm" wi="69.85mm" file="US20180118661A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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IMIDAZO ISOINDOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to an imidazo isoindole derivative, a preparation method therefor and a medical use thereof. In particular, the present invention relates to the imidazo isoindole derivative as shown in the formula (I), a preparation method and pharmaceutical composition containing the derivative, and a use thereof for treating diseases with a pathological characteristic of the IDO-mediated tryptophan metabolic pathways. The diseases comprise cancers, Alzheimer's disease, autoimmune diseases, depression, anxiety disorders, cataracts, psychological disorders and AIDS, wherein the substituents in the formula (I) are the same as those defined in the specification.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.61mm" wi="69.85mm" file="US20180118750A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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USE OF SRC PROTEIN INHIBITOR IN THE MANUFACTURE OF A MEDICAMENT FOR THE PROPHYLAXIS AND/OR TREATMENT OF ALZHEIMER'S DISEASE (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention provides use of a Src protein inhibitor N-(2-chloro-6-methylphenyl)-2-{6-[4-(3-hydroxyethyl)-1-piperazinyl]-2 -methyl-4-pyrimidinylamino}-5-thiazolecarboxamide (formula I) in the manufacture of a medicament for the prophylaxis and/or treatment of Alzheimer's disease. An Aβ42 oligomer and a tested drug were applied to primary isolated fetal mouse cerebral cortical neuron for 24 h to test the efficacy of the compound of formula I at different concentrations against Aβ42 oligomer toxicity in vitro, and the results show that the compound of formula I has a wide range of effective concentration and high cell viability at effective concentration.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.28mm" wi="76.12mm" file="US20180117043A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NON-PEPTIDIC GAPDH AGGREGATION INHIBITOR (Fri, 04 May 2018)
<p id="p-0001" num="0000">[Problem] Provided is a non-peptide compound, which can be used as a GAPDH aggregation inhibitor, [Solution] Provided is a GAPDH aggregation inhibitor including as an active ingredient a compound represented by the chemical formula 1 wherein R<sub>1</sub>, R<sub>2</sub>, and R<sub>3 </sub>are each independently a hydrogen atom, a halogen atom, or an aliphatic hydrocarbon group having a carbon number of from 1 to 10, a polysulfurized derivative thereof, or a pharmaceutically acceptable salt thereof. The present compound has a GAPDH aggregation inhibitory activity to suppress intracerebral aggregation of various proteins involved in cerebral neurodegenerative diseases, thereby contributing to improvement in various brain neurological diseases associated with aggregation of these proteins such as Alzheimer's disease, Parkinson's disease, and cerebral infarction, and prevention of advanced seriousness of these diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.09mm" wi="65.02mm" file="US20180116981A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL PIPERAZINE AND PIPERIDINE DERIVATIVES, THEIR SYNTHESIS AND USE THEREOF IN INHIBITING VDAC OLIGOMERIZATION, APOPTOSIS AND MITOCHONDRIA DYSFUNCTION (Fri, 04 May 2018)
<p id="p-0001" num="0000">Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's disease.</p>
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COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF IMIDAZOPYRAZINONES (Fri, 04 May 2018)
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of neurodegenerative disorders such as for example Alzheimer's Disease, Parkinson's Disease or Huntington's Disease. Separate aspects of the invention are directed to the combined use of said compounds for the treatment of neurodegenerative and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of neurodegenerative disorders.
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CRYSTAL OF BIS(8-QUINOLINAMINE) DERIVATIVES (Fri, 04 May 2018)
The present invention provides the crystal of compound N-butyl-2,2'-imino-bis(8-quinolinamine), pharmaceutical composition and use thereof. The crystal compound N-butyl-2,2'-imino-bis(8-quinolinamine) according to the present invention has an excellent property of the preparation of drugs, and can be used for treating abnormal metal ion metabolic-related diseases, as well as the diseases associated with abnormal Tau protein metabolism and abnormal beta-amyloid protein, for example, the neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, ataxia telangiectasia, Creutzfeldt-Jakob disease, Huntington's disease, spinocerebellar ataxia, multiple sclerosis (MS), Parkinson's disease, Alzheimer's disease (AD), primary lateral sclerosis (PLS) and the like.
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COMPOSITIONS, METHODS AND KITS FOR DETECTION OF GENETIC VARIANTS FOR ALZHEIMER'S DISEASE (Fri, 04 May 2018)
Provided herein are methods, kits, and devices related to genetic variations of neurological disorders. For example, methods, kits, and devices for using such genetic variations to assess susceptibility of developing Alzheimer's disease.
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POLYMORPHIC FORMS OF SODIUM BENZOATE AND USES THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present disclosure provides polymorphic forms of sodium benzoate with a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 5.9, 30.2, and 31.2 degrees; or a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 3.7, 5.9, and 26.6 degrees. Also provided herein are methods of preparing the polymorphic forms of sodium benzoate and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, or Alzheimer's disease).</p>
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IMIDAZODIAZEPINE COMPOUND (Thu, 26 Apr 2018)
[Problem] Provided is a compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM). [Means for Solution] The present inventors have studied a compound which has a positive allosteric modulating action (PAM action) on a dopamine D1 receptor and which can be used as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like. Thus, they have found that the imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and thereby completed the present invention. The imidazodiazepine compound of the present invention has a PAM action on a dopamine D1 receptor, and is expected to be an agent for preventing and/or treating cognitive impairment, schizophrenia negative symptom, CIAS, Parkinson's disease, Alzheimer's disease, Huntington's disease, depression, ADHD, drug dependency, or the like.
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DIKETONES AND HYDROXYKETONES AS CATENIN SIGNALING PATHWAY ACTIVATORS (Thu, 26 Apr 2018)
The present invention discloses ²-diketones, ³-diketones or ³-hydroxyketones or analogs thereof, that activate Wnt/²-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
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COMPOUNDS DERIVED FROM 3-ALKYLAMINE-1H-INDOLYL ACRYLATE AND THEIR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The invention relates to the methods for producing derivatives of 3-alkylamino-1H-indole acrylate (I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of the derivatives according to the invention for the treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulation of the activity of phase II genes activated by the factor Nrf2, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.</p>
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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Provided herein are certain substituted N-aryl and N-heteroaryl piperidine compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R 6 are as defined. The said novel compounds, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor(LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory disease and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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BENZOTHIAZOLE DERIVATIVES AS DYRK1 INHIBITORS (Fri, 20 Apr 2018)
The present invention relates to compounds of Formula (I), which are DYRK1A and/or DYRK1B inhibitors,and their use in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), metabolic disorders such as Metabolic Syndrome or diabetes mellitus, and cancer.
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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1,Q, and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Substituted aryl and heteroaryl ether compounds of the Formula (I) and pharmaceutically acceptable salts thereof, wherein X, R 1, R 2, R 3, L, R 4, L 1, Q, and R 5 are as defined herein. These compounds and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted N-aryl and N-heteroaryl piperidine compounds of the Formula (I): (Formula (I)) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1,Q, R5 and R6 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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Uridine diphosphate derivatives, prodrugs, compositions and uses thereof (Fri, 20 Apr 2018)
This disclosure relates to the use of uridine diphosphate (UDP) derivatives, salts and/or prodrugs thereof for the treatment of inflammatory conditions (e.g., psoriasis) and glaucoma, to prodrugs of UDP derivatives, compositions comprising therapeutically effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs for treating various disorders including, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma, and inflammatory conditions, e.g., psoriasis and rheumatoid arthritis.
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BIPHENYL-ETHYL-PYRROLIDINE DERIVATIVES AS HISTAMINE H3 RECEPTOR MODULATORS FOR THE TREATMENT OF COGNITIVE DISORDERS (Thu, 19 Apr 2018)
The present invention relates to biphenyl-ethyl-pyrrolidine derivatives of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that modulate the activity of the histamine H3 receptor (H3R): Compounds of the present invention and pharmaceutical compositions thereof are for use in methods for the treatment of histamine H3-associated disorders, such as treatment of cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as excessive daytime sleepiness, narcolepsy, shift-work sleep disorder, drowsiness as a side effect from a medication, maintenance of vigilance to aid in the completion of tasks and the like, cataplexy, hypersomnia, somnolence syndrome, jet lag, sleep apnea and the like, attention deficit hyperactivity disorder (ADHD), schizophrenia, allergies, allergic responses in the upper airway, allergic rhinitis, nasal congestion, dementia, Alzheimer's disease, pain and pruritus.
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PRODRUG OF 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to the compound (2R,2′R)-bis(((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl) 1,1′-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.</p>
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Chimeric compounds targeting proteins, compositions, methods, and uses thereof (Wed, 11 Apr 2018)
<p id="p-0001" num="0000">The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.</p>
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POTENT GAMMA-SECRETASE MODULATORS (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">Provided herein are compounds and methods for treating a disorder associated with aberrant A3 peptide levels, including Alzheimer's disease. Provided herein are compositions and methods for treating a disorder associated with aberrant Aβ peptide levels, including AD. Provided herein are compounds of Formula (A) or a pharmaceutically acceptable salt thereof, wherein, L′ is selected from the group consisting of C(O), C(R1)(R2), substituted or unsubstituted —C2-6 alkylene-, and substituted or unsubstituted —C3-6 cycloalkylene.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="70.10mm" file="US20180093967A1-20180405-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MATERIALS AND METHODS FOR DIAGNOSIS, PREVENTION AND/OR TREATMENT OF STRESS DISORDERS AND CONDITIONS ASSOCIATED WITH A-BETA PEPTIDE AGGREGATION (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The subject invention concerns materials and methods for treating and/or preventing diseases associated with accumulation of Aβ peptide in neural tissue. The subject invention also concerns materials and methods for treating and/or preventing stress disorders, such as post-traumatic stress disorder (PTSD). In one embodiment, a method of the invention comprises administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, to a person or animal in need of treatment. The methods of the invention can be used to prevent and/or treat Alzheimer's disease, Parkinson's disease, and/or Down's syndrome. The subject invention also concerns compositions that comprise cotinine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or adjuvant.</p> <p id="p-0002" num="0000">The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine. In one embodiment, the method comprises administering cotinine labeled with a detectable label to a person or animal. The presence of labeled cotinine in neural tissue is then determined. The level and/or location of cotinine can be analyzed and a diagnosis made. The subject invention also concerns cotinine labeled with a detectable label. In one embodiment, the cotinine is labeled with a radioisotope that can be detected by Positron Emission Tomography (PET) or single photon emission computed tomography (SPECT).</p>
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HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.</p>
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CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 06 Apr 2018)
The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from (II), (III), (IV), and (V), and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.
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URIDINE NUCLEOSIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE (Fri, 30 Mar 2018)
This disclosure relates to uridine nucleoside derivatives, compositions comprising therapeutically effective amounts of those nucleoside derivatives and methods of using those nucleoside derivatives or compositions in treating disorders that are responsive to compounds, such as agonists, of P2Y6 receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma and inflammatory conditions.
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HETEROCYCLIC COMPOUND (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present invention provides a compound having an MAGL inhibitory action, which is expected to be useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like.</p> <p id="p-0002" num="0000">The present invention relates a compound represented by the formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="69.85mm" file="US20180079756A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as described in the specification, or a salt thereof.</p>
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METHODS AND MATERIALS FOR REDUCING AMYLOID BETA LEVELS WITHIN A MAMMAL (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">This document provides methods and materials for reducing amyloid beta levels within a mammal (e.g. a mammal having Alzheimer's disease). For example, this document provides methods for using compositions containing a potato polysaccharide preparation to reduce one or more symptoms of Alzheimer's disease. In some cases, a composition containing a potato polysaccharide preparation provided herein can be used to increase binding, sequestration, and/or degradation of CNS-derived amyloid beta polypeptides, thereby inhibiting the formation of neurofibrillary plaques.</p>
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KETONE INHIBITORS OF LYSINE GINGIPAIN (Fri, 23 Mar 2018)
The present invention provides compounds according to Formula (I) as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium Porphyromonas gingivalis. Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease.
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COMPOSITIONS AND METHODS FOR TREATING BETA-AMYLOID RELATED DISEASES (Thu, 22 Mar 2018)
In alternative embodiments the invention provides compositions and methods for ameliorating diseases and conditions having a beta-amyloid component, including Alzheimer's disease (AD), Vascular Dementia (VD), dementia, pre-dementia, Cognitive Dysfunction Syndrome (CDS) and loss of cognition in humans and in non-human animal. In alternative embodiment the invention provides analogs of AB-007 and its acid form E64c (loxistatin), their preparation, and pharmaceutical compositions thereof and methods of making and using same. In alternative embodiments compositions of the invention are deuterated analogs of AB-007 (or E64d) and E64c (or loxistatin). In alternative embodiments compositions of the invention are metabolically blocked forms as compared to AB-007 and loxistatin.; In alternative embodiments compositions of the invention are used to ameliorate (including treat, slow, reverse or prevent) a disease or condition which can be ameliorated by partial or complete inhibition of a cysteine protease, e.g., AD, VD, CDS. The invention also provides alternative dosage forms and formulations for AB-007 and loxistatin, and for compounds of this invention, which can be used e.g., to treat AD, VD and CDS, in humans and in non-human animals.
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2 (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 2 (mGlu<sub>2</sub>), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, anxiety, obsessive-compulsive disorder, cognitive disorders, Alzheimer's disease, or autism spectrum disorders in a subject.</p>
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METHODS AND COMPOSITIONS FOR TREATING DEGENERATIVE AND ISCHEMIC DISORDERS (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.</p>
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PYRROLO[2,3-C]PYRIDINES AS IMAGING AGENTS FOR NEUROFIBRILARY TANGLES (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">The present invention is directed to pyrrolopyridine compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.71mm" wi="58.59mm" file="US20180071412A1-20180315-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.</p>
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BIOMARKERS FOR THE DIAGNOSIS AND CHARACTERIZATION OF ALZHEIMER'S DISEASE (Fri, 16 Mar 2018)
Embodiments of the present disclosure relate generally to the analysis and identification of global metabolic changes in Alzheimer's disease (AD). More particularly, the present disclosure provides materials and methods relating to the use of metabolornics as a biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. Defining metabolic changes during AD disease trajectory and their relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.
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ALLOSTERIC CORTICOTROPIN-RELEASING FACTOR RECEPTOR 1 (CRFR1) ANTAGONISTS THAT DECREASE P-TAU AND IMPROVE COGNITION (Fri, 16 Mar 2018)
In various embodiments novel allosteric antagonists of the CRFR1 receptor are provided. It discovered that allosteric CRFR1 receptor antagonists are effective to modulate p-Tau levels in Alzheimer's disease (AD) models.
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AND 1,1,1-TRIFLUORO-4-HYDROXYBUTAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.32mm" wi="69.85mm" file="US20180065943A1-20180308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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THERAPEUTIC COMPOUNDS (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The invention provides compounds formula (I) and salts thereof: wherein R1-R4 have any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, inflammation, hyperresponsiveness, allergic conditions, asthma, and psychotic disorders such as schizophrenia. The compounds are also useful to lower IL-4, IL-5, or IL-15 levels in an animal.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="53.09mm" file="US20180065936A1-20180308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.</p>
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IGF-1R SIGNALING PATHWAY INHIBITORS USEFUL IN THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The present invention provides compounds acting as Insulin/IGF signaling modulators useful in the treatment of neurodegenerative diseases and disorders. The invention provides pharmaceutical compositions including such compounds, and methods of using these compounds and compositions for the treatment of neurodegenerative diseases, in particular neurodegenerative diseases caused by proteotoxicity such as Alzheimer's disease.</p>
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INHIBITORS OF DUAL LEUCINE ZIPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 09 Mar 2018)
Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy -induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).
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MACROPHAGES/MICROGLIA IN NEURO-INFLAMMATION ASSOCIATED WITH NEURODEGENERATIVE DISEASES (Fri, 09 Mar 2018)
Described herein are methods of treating neuron inflammation conditions, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of cromolyn or a cromolyn derivative compound.
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Synthesis and Utility of New Capgroup Largazole Analogs (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.</p>
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INHIBITORS OF DUAL LEUCINE ZIPPER (DLK) KINASE FOR THE TREATMENT OF DISEASE (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds which inhibit the kinase activity of dual leucine zipper (DLK) kinase (MAP3K12), pharmaceutical compositions, and methods of treatment of DLK-mediated diseases, such as neurological diseases that result from traumatic injury to central nervous system and peripheral nervous system neurons (e.g. stroke, traumatic brain injury, spinal cord injury), or that result from a chronic neurodegenerative condition (e.g. Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, progressive supranuclear palsy, Lewy body disease, Kennedy's disease, and other related conditions), from neuropathies resulting from neurological damage (chemotherapy-induced peripheral neuropathy, diabetic neuropathy, and related conditions) and from cognitive disorders caused by pharmacological intervention (e.g. chemotherapy induced cognitive disorder, also known as chemobrain).</p>
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6-SUBSTITUTED ESTRADIOL DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 02 Mar 2018)
A method of treating Alzheimer's Disease (AD) with 6-substituted estradiol compounds and their pharmaceutically acceptable salts or prodrugs. The compounds provide for up-regulation of lipoprotein lipase (LPL) and/or apoliprotein C2 (ApoC2), the protein that activates LPL.
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7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto (Fri, 02 Mar 2018)
In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8 substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.
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HETEROCYCLIC COMPOUND (Thu, 01 Mar 2018)
The present invention provide a compound having an orexin receptor antagonistic activity, which is expected to be useful as medicaments such as agents for the prophylaxis or treatment of sleep disorder, depression, anxiety disorder, panic disorder, schizophrenia, drug dependence, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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IMIDAZO ISOINDOLE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF (Thu, 01 Mar 2018)
The present invention relates to an imidazo isoindole derivative, a preparation method therefor and a medical use thereof. In particular, the present invention relates to the imidazo isoindole derivative as shown in the formula (I), a preparation method and pharmaceutical composition containing the derivative, and a use thereof for treating diseases with the pathological characteristic of IDO-mediated tryptophan metabolic pathways. The diseases comprise cancers, Alzheimer's disease, autoimmune diseases, depression, anxiety disorders, cataracts, psychological disorders and AIDS, wherein the substituents in the formula (I) are the same as those defined in the description.
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HETEROCYCLIC COMPOUND (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.75mm" wi="53.09mm" file="US20180050996A1-20180222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the attached DESCRIPTION.</p>
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ANTIBODY HIGHLY SPECIFICALLY RECOGNIZING TURN STRUCTURE AT 22- AND 23-POSITIONS IN AMYLOID BETA (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">Provided is an antibody or an immunologically reactive fragment thereof which targets exclusively an Aβ having a specific turn structure of Aβ (a toxic conformer of Aβ). Also provided are a medicinal composition comprising, as an active ingredient, an antibody that specifically recognizes a toxic conformer of Aβ, a kit for assaying a toxic conformer of Aβ, a diagnostic agent for Alzheimer's disease, etc.</p>
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5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE (Fri, 23 Feb 2018)
The present invention relates to compounds of Formula A and pharmaceutical compositions thereof that modulate the activity of the 5-HT2C receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of a 5-HT2C receptor-mediated disorder, such as, weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction and the like, obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders, urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a compound herein, optionally in combination with a supplemental agent.
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INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF (Thu, 22 Feb 2018)
Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
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Method of Treating Neurological Conditions with Extract of Nerium Species or Thevetia Species (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">A method of treating neurological condition in a subject by administration of a neuroprotective composition of a mixture of two or more triterpenes. Alzheimer's disease, Huntington's disease, stroke or Parkinson's disease are treated by administering a therapeutically effective amount of the neuroprotective composition to a subject.</p>
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COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.</p>
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METHOD OF DIAGNOSIS, PROGNOSIS OR TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">Methods for the diagnosis and prognosis of neurodegenerative diseases, such as a Tauopathy or Alzheimer's disease, are described. Compositions and methods for the treatment of neurodegenerative diseases are also described.</p>
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METHODS FOR TREATING PROTEINOPATHIES (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">This disclosure relates to a method of treating a proteinopathy in a subject, the method comprising administering to the subject an effective amount of a quinuclidine compound. The disclosure also relates to a method of reducing, reversing or preventing the accumulation of protein aggregates in tissue of a subject diagnosed as having a proteinopathy, or being at risk of developing a proteinopathy, the method comprising administering to the subject an effective amount of a quinuclidine compound. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods. The proteinopathy may be a synucleinopathy or a tauopathy, such as Parkinson's disease, Alzheimer's disease or dementia with Lewy bodies.</p>
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Oxazine Derivative for Use in the Prevention of Alzheimer's Disease in at Risk Patients (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to an oxazine derivative BACE-1 inhibitor and pharmaceutical compositions comprising such oxazine derivative for use in the prevention of Alzheimer's disease in a patient at risk of developing clinical symptoms of Alzheimer's disease, and in particular, wherein the patient at risk of developing clinical symptoms of Alzheimer's disease carries one or two copies of the ApoE4 allele.</p>
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INHIBITORS OF JUN N-TERMINAL KINASE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.36mm" wi="18.88mm" file="US20180037577A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt or solvate thereof, wherein ring A, C<sup>a</sup>, C<sup>b</sup>, Z, R<sup>5</sup>, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.</p>
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GP130 MODULATORS (Fri, 09 Feb 2018)
There are provided, inter alia, compounds and methods useful for the treatment of neurological conditions, such as neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
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HETEROCYCLIC COMPOUND (Thu, 08 Feb 2018)
The present invention provides a compound having an MAGL inhibitory action, which is expected to be useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates a compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof.
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Allosteric modulators of nicotinic acetylcholine receptors (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.65mm" wi="69.85mm" file="US09926285-20180327-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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STABLE AMYLOID BETA MONOMERS AND OLIGOMERS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.</p>
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THIOFLAVIN DERIVATIVES FOR USE IN ANTEMORTEM DIAGNOSIS OF ALZHEIMER'S DISEASE AND IN VIVO IMAGING AND PREVENTION OF AMYLOID DEPOSITION (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">This invention relates to novel thioflavin derivatives, methods of using the derivatives in, for example, in vivo imaging of patients having neuritic plaques, pharmaceutical compositions comprising the thioflavin derivatives and method of synthesizing the compounds. The compounds find particular use in the diagnosis and treatment of patients having diseases where accumulation of neuritic plaques are prevalent. The disease states or maladies include but are not limited to Alzheimer's disease, familial Alzheimer's disease, Down's Syndrome and homozygotes for the apolipoprotein E4 allele.</p>
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GLYCINE METABOLISM MODULATORS AND USES THEREOF (Fri, 02 Feb 2018)
The present invention relates to a compound of general formula (I) and/or its solvates, hydrates and pharmaceutically acceptable salts, which are modulators of glycine metabolism. The present invention also relates to the methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of disorders/conditions/diseases involving, relating to or associated with glycine metabolism or a pathway where glycine decarboxylase (GLDC, or glycine cleavage system) plays a role. In a preferred embodiment the disorders/conditions/disease is cancer, inflammatory conditions, Alzheimer's disease, metabolic disorders and CNS disorders.
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Compounds (Fri, 02 Feb 2018)
COMPOUNDS The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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Compounds (Fri, 02 Feb 2018)
COMPOUNDS The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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Co-crystals of substituted glycine and uses thereof (Wed, 31 Jan 2018)
<p id="p-0001" num="0000">The present disclosure provides co-crystals of a substituted glycine compound and a co-former compound of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.45mm" wi="69.85mm" file="US09877942-20180130-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> compositions comprising such, and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, suicidal ideation and/or behavior, obsessive compulsive disorder or Alzheimer's disease). Also provided herein are methods for preparing the co-crystals. </p>
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NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu3), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.</p>
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COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES (Fri, 26 Jan 2018)
The present invention relates to novel compounds of the formula (II) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.
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COMPOUNDS FOR IMAGING TAU PROTEIN AGGREGATES (Fri, 26 Jan 2018)
The present invention relates to novel compounds of the formula (I) that can be employed in the selective Tau detection of disorders and abnormalities associated with Tau aggregates such as Alzheimer's disease and other tauopathies using Positron Emission Tomography (PET) Imaging.
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ISOQUINOLINE DERIVATIVES AS PERK INHIBITORS (Fri, 26 Jan 2018)
The invention is directed to substituted isoquinoline derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states: (I) wherein R1, R2, R3, R4, R5, R6, R7 and X are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, ather osclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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AN OXAZINE DERIVATIVE FOR USE IN THE PREVENTION OF ALZHEIMER'S DISEASE IN AT RISK PATIENTS (Fri, 26 Jan 2018)
The present invention relates to an oxazine derivative BACE-1 inhibitor and pharmaceutical compositions comprising such oxazine derivative for use in the prevention of Alzheimer's disease in a patient at risk of developing clinical symptoms of Alzheimer's disease, and in particular, wherein the patient at risk of developing clinical symptoms of Alzheimer's disease carries one or two copies of the ApoE4 allele.
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Antibodies Specific for Hyperphosphorylated Tau and Methods of Use Thereof (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to a class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396) with improved affinity, as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and other tauopathies.</p>
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FUSED PYRIMIDINE DERIVATIVES (Fri, 19 Jan 2018)
The present invention relates to a compound of formula (I) wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, -CH2-C3-6-cycloalkyl or bridged C4-6-cycloalkyl, substituted by one, two or three halogen atoms, or by lower alkyl or lower alkyl substituted by halogen;R2 is a five or six membered heteroaryl group, selected from or wherein R6 is hydrogen, lower alkyl, halogen or lower alkoxy; and R7 is hydrogen, lower alkoxy or halogen; R3 is lower alkyl or lower alkyl substituted by hydroxy: R4 is hydrogen or lower alkyl; R5 is hydrogen or lower alkyl; n is 1 or 2; -( )n- is -CH2- or -CH2CH2- for n being 1 or 2; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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Novel Forms of [R-(R*,R*)]-2-(4-Fluorophenyl)-Beta, Gamma-Dihydroxy-5-(1-Methylethyl)-3-Phenyl-4-[(Phenylamino)carbonyl]-1H-Pyrrole-1-Heptanoic Acid Calcium Salt (2:1) (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Novel forms of [R-(R*,R*)]-<b>2</b>-(<b>4</b>-fluorophenyl)-β,δ-dihydroxy-<b>5</b>-(<b>1</b>-methylethyl)-<b>3</b>-phenyl-<b>4</b>-[(phenylamino)carbonyl]-<b>1</b>H-pyrrole-<b>1</b>-heptatonic acid hemi calcium salt designated Form XX, Form XXI, Form XXII, Form XXIII, Form XXIV, Form XXV, Form XXVI, Form XXVII, Form XXVIII, Form XXIX, and Form XXX, characterized by their X-ray powder diffraction, solid-state NMR, and/or Raman spectroscopy are described as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia (BPH) and Alzheimer's disease.</p>
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FUSED PYRIMIDINE DERIVATIVES (Fri, 12 Jan 2018)
The present invention relates to compounds of formula (I), wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, -CH2-C3-6-cycloalkyl, or bridged C3-5-cycloalkyl, optionally substituted by one, two or three substituents, selected from halogen, lower alkyl or lower alkyl substituted by halogen; R2 is hydrogen, halogen, lower alkoxy, lower alkyl substituted by halogen or lower alkoxy substituted by halogen; R3 is a five membered heteroaryl group, selected from (A), (B), (C), (D); wherein R6 is hydrogen or lower alkyl; R7 is halogen or lower alkyl; R8 is hydrogen or lower alkyl; R9 is hydrogen or lower alkyl; R4 is lower alkyl or lower alkyl substituted by hydroxy; R5/R5' is independently from each other hydrogen or lower alkyl; -( )n- is –CH2- or –CH2CH2- for n being 1 or 2; X is CH or N; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.
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NITROGEN-CONTAINING HETEROCYCLIC COMPOUND (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.29mm" wi="69.85mm" file="US20180000780A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as described in the specification, or a salt thereof.</p>
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COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia.</p>
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5,7-Dihydro-Pyrrolo-Pyridine Derivatives (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.47mm" wi="76.20mm" file="US20180002331A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R<sup>1</sup>, R<sup>2</sup>, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.</p>
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5,7-DIHYDRO-PYRROLO-PYRIDINE DERIVATIVES FOR TREATING NEUROLOGICAL AND NEURODEGENERATIVE DISEASES (Fri, 05 Jan 2018)
The present invention provides, in part, compounds of Formula (I): or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N- oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4- associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.
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BICYCLO[3.2.1]OCTYL AMIDE DERIVATIVES AS ALLOSTERIC MODULATORS OF THE METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLU5 OR MGLUR5) FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM (CNS) DISORDERS (Thu, 04 Jan 2018)
The present invention provides bicyclo[3.2.1]octyl amide derivatives of formula (I): wherein L, R 1 and R 2 are as defined herein, as allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 or mGluR5) for the treatment of central nervous system (CNS) disorders, such as e.g. mood disorders, anxiety, schizophrenia, Alzheimer's disease, Parkinson's disease and multiple sclerosis.
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3.ALPHA.-ETHYNYL, 3.BETA.-HYDROXY-5.ALPHA.-PREGNAN-20-OXIME FOR USE IN THE TREATMENT OF CNS DISORDERS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention relates to 3α-ethynyl, 3β-hydroxy, 5α-pregnan-20-oxime or a pharmaceutically acceptable salt thereof, which compounds and/or salts are useful as modulators of the mammal brain excitability via the gamma-5 aminobutyric acid receptor-chloride ionophore (GABA<sub>A</sub>-R) complex and in the treatment of disorders such as hepatic encephalopathy, Down's syndrome and Alzheimer's disease.</p>
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IMINOTHIADIAZINE DIOXIDES BEARING AN AMINE-LINKED SUBSTITUENT AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>1</sup>, R<sup>2</sup>, ring A, R<sup>A</sup>, m, ring B, R<sup>B</sup>, and n are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.23mm" wi="59.10mm" file="US20170369484A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MAP KINASE MODULATORS AND USES THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention provides for novel MAP kinase inhibitors and compositions comprising the same. In some embodiments, the MAP kinase inhibitors are p38α MAP kinase inhibitors. The invention further provides for methods for treatment of diseases comprising administration of MAP kinase inhibitors or compositions comprising MAP kinase inhibitors. In some embodiments, the disease is Alzheimer's Disease, ALS, Huntington's Disease or Parkinson's Disease.</p>
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N-(SUBSTITUTED-PHENYL)-SULFONAMIDE DERIVATIVES AS KINASE INHIBITORS (Fri, 29 Dec 2017)
The invention relates to N-(substituted-phenyl)-sulfonamide compounds, which are extremely useful as inhibitors of protein kinases (e.g. PERK kinase) and accordingly can be used for the treatment of cell proliferative disorders, such as cancer, or diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
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NEW THIOSEMICARBAZONE COMPOUNDS AND ANALOGUES THEREOF (Fri, 29 Dec 2017)
The present invention relates to new multi-functional compounds that are useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing neurodegenerative diseases.
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2,3,4,5-TETRAHYDROPYRIDIN-6-AMINE AND 3,4-DIHYDRO-2H-PYRROL-5-AMINE COMPOUND INHIBITORS OF BETA-SECRETASE (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to 2,3,4,5-tetrahydropyridin-6-amine and 3,4-dihydro-2H-pyrrol-5-amine compound inhibitors of beta-secretase having the structure shown in Formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="44.45mm" file="US20170362198A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein the radicals are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease, dementia associated with beta-amyloid, age-related macular degeneration, type 2 diabetes or metabolic disorders.</p>
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C5-C6-OXACYCLIC FUSED IMINOPYRIMIDINONE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminopyrimidinone compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>N</sup>, R<sup>1</sup>, R<sup>A</sup>, ring A, m, n, -L<sub>1</sub>-, ring B, R<sup>B</sup>, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.36mm" wi="70.27mm" file="US20170362248A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CO-CRYSTALS OF SODIUM BENZOATE AND USES THEREOF (Fri, 22 Dec 2017)
Provided are co-crystals of a sodium benzoate compound and a co-former compound of Formula (I). Also provided herein are methods of preparing the co-crystals and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, or Alzheimer's disease) or a glucose or lipid metabolic disorder (e.g., obesity, diabetes, hypercholesterolemia, hypertension, or hyperlipidemia).
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ADAMANTANE COMPOUNDS (Fri, 22 Dec 2017)
The present invention relates to new multi-functional compounds that are useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing neurodegenerative diseases.
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DISRUPTION OF THE INTERACTION BETWEEN AMYLOID BETA PEPTIDE AND DIETARY LIPIDS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to methods of treating neurodegenerative disorders associated with Alzheimer's disease (AD), Parkinson's disease (PD) and synucleinopathies, such as dementia with Lewy bodies, Down Syndrome (DS) and associated cognitive disorders, multiple system atrophy, and rare neuroaxonal dystrophies, such as Niemann-Pick type C disease (NPC) and Gaucher's disease comprising administering an inhibitor to disrupt the interaction between Aβ or αS and neuronal lipids. The invention further relates to assays for identifying agents that reduce interaction between Aβ or αS and neuronal lipids. Lastly, the invention relates to methods and compositions for intranasal administration of fatty acids or lipids containing fatty acid acyl chains of dietary lipids for promoting central nervous system health and/or prevention or treatment of neurodegenerative disorders.</p>
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DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">Provided herein are compounds of formula (I) and compositions containing the compounds. The compounds and compositions are useful in the methods of treating, amelioration or prophylaxix of diseases associated with Nrf2/NF-<sub>κ</sub>B pathways. The diseases associated include, but are not limited to a fibrotic disease such as lung fibrosis, liver fibrosis, kidney fibrosis, and scleroderma, or a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, and sickle cell disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.69mm" wi="57.40mm" file="US20170354639A1-20171214-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SULFUR-CONTAINING COMPOUNDS TARGETING VESICULAR ACETYLCHOLINE TRANSPORTER (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The present invention generally relates to various compounds that are useful as vesicular acetylcholine transporter (VAChT) ligands. The invention further relates to methods of using these compounds and their radiolabeled analogs for the detection of neurodegenerative diseases including Parkinson's disease (PD), and Alzheimer's disease (AD).</p>
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STABLE AMYLOID BETA MONOMERS AND OLIGOMERS (Fri, 15 Dec 2017)
<p id="p-0001" num="0000">The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.</p>
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CHEMCICAL COMPOUNDS (Fri, 15 Dec 2017)
The invention is directed to substituted pyrrolidine derivatives. Specifically, the invention is directed to compounds according to Formula III: wherein A, B, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, R10, R30, Y1, Y2, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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CHEMICAL COMPOUNDS AS ATF4 PATHWAY INHIBITORS (Fri, 15 Dec 2017)
The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: wherein A, B, X, Y, L1, L2, L3, R1, R2, R3, R4, R5, R6, R9, z2, z4, z5, and z6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-D]PYRIMIDINES AS LRRK2 INHIBITORS (Thu, 14 Dec 2017)
The present invention provides novel 4,5-disubstituted-7 H -pyrrolo[2,3- d ]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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3-(6-alkoxy-5-chlorobenzo[d]isoxazol-3-yl)propanoic acid useful as kynurenine monooxygenase inhibitors (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.37mm" wi="58.42mm" file="US09932328-20180403-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or ═O; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl; <br/> and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure. </li> </ul> </li> </ul> </p>
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PROCESS FOR PREPARING N-(5-(3-(7-(3-FLUOROPHENYL)-3H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-INDAZOL-5-YL)PYRIDIN-3-YL)-3-METHYLBUTANAMIDE (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Provided herein is a synthetic process for preparing a compound of Formula (1).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.78mm" wi="68.58mm" file="US20170349584A1-20171207-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The disclosure also provides useful intermediates and salts, amorphous and polymorph forms of the compound of Formula (1). These compounds are useful for various disease including cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, and osteoarthritis as well as Wnt-related diseases.</p>
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COMPETITIVE INHIBITORS OF INVARIANT CHAIN EXPRESSION AND/OR ECTOPIC CLIP BINDING (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The invention relates to methods for modulating the immune function through targeting of CLIP molecules. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including autoimmune disease, cancer, Alzheimer's disease, allergic disease, transplant and cell graft rejection, HIV infection and other viral, bacterial, and parasitic infection, and AIDS. Methods are also provided for preparing a peptide having the property of being able to displace CLIP by feeding one or more peptide sequences into software that predicts MHC Class II binding regions in an antigen sequence and related products.</p>
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HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to novel hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., Syndrome X), thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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Inhibitors of lysine gingipain (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention relates generally to therapeutics targeting the bacterium <i>Porphyromonas gingivalis</i>, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with <i>P. gingivalis </i>infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.31mm" wi="69.85mm" file="US09988375-20180605-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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4H-pyran compounds as insulin-regulated aminopeptidase (IRAP) inhibitors (Fri, 24 Nov 2017)
The present disclosure relates to <i>4H</i>-pyran compounds of formula (I) and their use in therapy, to compositions and agents comprising said compounds, to methods of treatment using said compounds, and their use in the manufacture of medicaments. The disclosure further relates to said compounds and compositions thereof as inhibitors of IRAP and their use in the treatment or prevention of Alzheimer's disease and the treatment and prevention of memory and cognitive disorders.
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CAMSYLATE SALT (Fri, 24 Nov 2017)
A camsylate salt of (1r,1'R,4R)- 4-methoxy-5 "-methyl-6'-[5 -(prop-i -yn- 1 -yl)pyridin-3 -yl] 3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine, pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating AB-related pathologies such as Alzheimer's Disease, Down's syndrome, B-amyloid angiopathy and conditions such as dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
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COMPOUNDS TO PROMOTE NORMAL PROCESSING OF APP (Fri, 17 Nov 2017)
In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of compound C41 to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly enhances sAPPα, lowers Aβ, p-Tau, inhibits the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) and improves memory in a mammal are provided.
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INHIBITION OF BETA-2 NICOTINIC ACETYLCHOLINE RECEPTORS TO TREAT ALZHEIMER'S DISEASE PATHOLOGY (Fri, 17 Nov 2017)
The invention provides methods of reducing development of mild cognitive impairment and/or learning disorders and/or memory disorders in a subject suspected to have or suffering from Alzheimer's disease (AD). In some embodiments,the methods comprise administering a therapeutically effective amount of a beta-2 nicotinic acetylcholine receptor (n AChR) antagonist and/or beta-2 nAChRnegative allosteric modulator (NAM) to the subject over a therapeutic dosing period to thereby reduce the rate of development of mild cognitive impairment and/or learning disorders and/or memory disorders in the subject over the therapeutic dosing period.
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Compounds and their use as BACE inhibitors (Fri, 10 Nov 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.</p>
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ISOTOPICALLY MODIFIED COMPOSITION AND THERAPEUTIC USES THEREOF (Fri, 10 Nov 2017)
This disclosure relates to isotopically modified amino acids and their pharmaceutical or nutritional uses in stabilizing pharmaceutical protein-based formulations, proteins with long life span, and preventing or treating disease such as Alzheimer's disease. Specifically, the disclosure provides protein drugs having increased stability comprising an L-aspartate (L-Asp) residue or an L-asparagine (L-Asn) residue, wherein the L-Asp residue or the L-Asn residue comprises a deuterium atom.
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TRIFLUOROACETHYDRAZIDE COMPOUND AS WELL AS PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN PREPARING MEDICAMENT (Thu, 09 Nov 2017)
The present invention relates to trifluoroacetyl hydrazide compounds and methods of preparation and uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells.. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">The present application relates to compounds of formula (I), (Ia), or (Ib) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.</p>
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2-Amino-3,5-Difluoro-3,6-Dimethyl-6-Phenyl-3,4,5,6-Tetrahydropyridines as BACE1 Inhibitors for Treating Alzheimer's Disease (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">The present invention is directed to compounds according to Formula (I) which compounds are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for 5 which the reduction of Aβ deposits is beneficial such as Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.75mm" wi="69.85mm" file="US20170313658A1-20171102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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AMYLOID BINDING AGENTS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">There are provided compounds and methods for the detection of amyloids and treatment of diseases related to amyloids including Alzheimer's disease and other related amyloid-based neurodegenerative diseases.</p>
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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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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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ANTIBODY HIGHLY SPECIFICALLY RECOGNIZING TURN STRUCTURE AT 22- AND 23-POSITIONS IN AMYLOID BETA (Thu, 02 Nov 2017)
Provided is an antibody or an immunologically reactive fragment thereof which targets exclusively an A² having a specific turn structure of A² (a toxic conformer of A²). Also provided are a medicinal composition comprising, as an active ingredient, an antibody that specifically recognizes a toxic conformer of A², a kit for assaying a toxic conformer of A², a diagnostic agent for Alzheimer's disease, etc.
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Pro-Neurogenic Compounds (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.</p>
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TETRAHYDRONAPHTHYRIDINE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R<sup>1</sup>, R<sup>2</sup>, L, X<sub>1</sub>, X<sub>2</sub>, and X<sub>3</sub>, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="61.38mm" file="US20170305902A1-20171026-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.</p>
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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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HETEROCYCLIC COMPOUND (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention provides a compound having an MAGL inhibitory action, and useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.45mm" wi="69.85mm" file="US20170283406A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as defined in the specification, or a salt thereof.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula Ia:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.46mm" wi="62.48mm" file="US20170283423A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metastases, gastrointestinal stromal tumors, and giant cell tumors.</p>
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Process for large scale production of 1-isopropyl-3-{5-[1-(3-methoxypropyl)piperidin-4-YL]-[1,3,4]oxadiazol-2-YL}-1H-indazole oxalate (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a process suitable for adoption to large scale manufacture of 1-isopropyl-3-{5-[1-(3-methoxypropyl)piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate of formula (I), which is a selective 5-HT<sub>4 </sub>receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.</p>
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HETEROCYCLIC COMPOUND (Fri, 06 Oct 2017)
The present invention provides a compound having an MAGL inhibitory action, and useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates to a compound represented by the formula (I) : wherein each symbol is as defined in the specification, or a salt thereof.
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Pharmaceutical compounds and use of same in cancer and tauopathies (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (l)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.</p>
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Dosing Regimens for Treating And/Or Preventing Cerebral Amyloidoses (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).</p>
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ALKYLIDENE PHOSPHONATE ESTERS AS P-GLYCOPROTEIN INDUCERS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to the alkylidene phosphonate esters of formula I wherein, R<sub>1 </sub>is selected from a group consisting of hydrogen or alkyl group; R<sub>2 </sub>is selected from a group consisting of hydrogen, hydroxy, alkyl, alkoxy, nitro, halogen, amino, N-substituted alkylamino; alkyl group is selected from a group consisting of methyl, ethyl and isopropyl; Ar is selected from a group consisting of aryl, substituted aryl, fused aryl, heteroaryl, and substituted heteroaryl. The present invention particularly relates to synthesis and p-glycoprotein induction activity of the alkylidene phosphonate esters. In addition, the invention relates to methods of using compounds for treating or preventing Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="52.24mm" file="US20170275314A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula I: R1-L1-C(A)(A′)-CH<sub>2</sub>, -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.</p>
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Allosteric modulators of nicotinic acetylcholine receptors (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.65mm" wi="69.85mm" file="US09840481-20171212-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS (Fri, 29 Sep 2017)
The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
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Prodrug of 1,1′-(1,6-dioxo -1,6-hexanediyl)bis-D-proline (Fri, 22 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to the compound (2R,2′R)-bis(((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl) 1,1′-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.</p>
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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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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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γ-diketones as Wnt/β-catenin signaling pathway activators (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.</p>
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Nitrogen-containing heterocyclic compound (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I) or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.98mm" wi="54.02mm" file="US09789084-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein each symbol is as described in the specification, <br/> or a salt thereof. </p>
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S-imino-S-oxo iminothiazine compounds as bace inhibitors, compositions, and their use (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2A</sup>, R<sup>2B</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>N</sup>, ring A, R<sup>A</sup>, m, ring B, R<sup>B</sup>, and n are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.18mm" wi="61.89mm" file="US09957269-20180501-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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BACE 1 INHIBITORS (Sat, 09 Sep 2017)
The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compound of the present invention is useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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PIPERIDINE DERIVATIVE AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention provides N-[1-(1-Cyclohexyl-3,5-dimethyl-1H-pyrazole-4-sulfonyl)-4-phenyl-piperidin-4-ylmethyl]-N-isobutyl-4-{[(piperidin-4-ylmethyl)-amino]-methyl}-benzenesulfonamide and pharmaceutically acceptable salts thereof. These compounds may be useful in the treatment of diseases such as Alzheimer's disease or renal failure. The present invention further relates to methods for the preparation of compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the use of such compounds and/or pharmaceutical compositions in treating certain diseases.
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M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR COMPOUNDS AND METHODS OF USE THEREOF (Sat, 09 Sep 2017)
The present invention is directed to compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Q, X, Y, Z, R1, R7 and n are defined herein. The compounds of Formula (I) are M1 receptor positive allosteric modulators that are useful in the treatment of diseases in which the M1 receptor is involved, including Alzheimer's disease, schizophrenia, pain and sleep disorders. The invention also relates to pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, and to methods of using the compounds of Formula (I) in the treatment of diseases mediated by the M1 receptor.
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Therapeutic agent for Alzheimer's disease (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention aims to provide a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease, which has a novel action mechanism and shows less side effects. A polyphenol derivative having liposolubility enhanced by the introduction of at least one kind of a liposoluble group selected from the group consisting of a chain saturated hydrocarbon group, a chain unsaturated hydrocarbon group, a cyclic saturated hydrocarbon group, a cyclic unsaturated hydrocarbon group, an aromatic hydrocarbon group, a liposoluble vitamin residue and a sterol residue has an action to potentiate neprilysin activity, and is useful as a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease.</p>
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Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof (Fri, 08 Sep 2017)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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β- and γ-diketones and γ-hydroxyketones as <i>WNT</i>/β-catenin signaling pathway activators (Fri, 01 Sep 2017)
<p id="p-0001" num="0000">The present application discloses a compound which is</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.83mm" wi="54.02mm" file="US09884053-20180206-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> which activates Wnt/β-catenin signaling and thus treats or prevents diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases. </p>
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Diazine-fused amidines as BACE inhibitors, compositions, and their use (Fri, 01 Sep 2017)
<p id="p-0001" num="0000">In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R<sup>1A</sup>, R<sup>1B</sup>, R<sup>2</sup>, R<sup>A</sup>, ring A, R<sup>A</sup>, m, L<sub>1</sub>, R<sup>L</sup>, ring C, R<sup>C</sup>, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.50mm" wi="60.28mm" file="US09868738-20180116-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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2-amino-3,5-difluoro-3,6-dimethyl-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 inhibitors for treating alzheimer's disease (Sat, 19 Aug 2017)
The present invention is directed to compounds according to Formula (I) which compounds are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for 5 which the reduction of A[beta] deposits is beneficial such as Alzheimer's disease.
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Pyrrolidine-2,4-diketone compound and preparation method thereof (Sat, 19 Aug 2017)
The invention relates to a novel compound and a preparation method thereof. A structure general formula is shown as a formula I. An animal experiment verifies that the compound provided by the invention has the memory effect of saving an animal model, is high in safety, has no induced mutagenicity and can stay for several hours in blood after oral administration and intravenous injection, enter a brain and be used for preparing a drug for treating an Alzheimer's disease.
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Lipoic acid-tacrine similar gene heterodimer and application thereof for curing Alzheimer's disease (Sat, 19 Aug 2017)
The invention relates to a tacrine similar gene, a series of lipoic acid-tacrine similar gene heterodimer and a stereisomer thereof, a tautome, a nitric oxide, a solvate and a pharmaceutically acceptable salt or prodrug, which are of selectivity chelated copper ions, and inhibit the multi-target effect for cholinesterase and nerve cell protection. The invention also relates to a method for preparing the compound and application for curing and preventing Alzheimer's disease.
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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="US09896438-20180220-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </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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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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(1H-pyrazolo[3,4-d]pyrimidine)-4-amino derivative and application of same as IDO inhibitor to drug preparation (Sat, 29 Jul 2017)
The invention discloses a (1H-pyrazolo[3,4-d]pyrimidine)-4-amino derivative and a preparation method thereof, and application of the derivative as an IDO inhibitor. The derivative provided by the invention can be used for preventing and/or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections related to cellular immune activation, autoimmune diseases, AIDS, cancers, depression or metabolic disorder of tryptophan.
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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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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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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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Cholinesterase Inhibitors (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">The invention provides compounds that inhibit cholinesterases, such as acetylcholinesterase and butyrylcholinesterase. Such compounds are useful to prevent or treat exposure of a patient (e.g., a human) to an organophosphoric nerve agent (e.g., sarin and VX) or to treat a patient suffering from a neurodegenerative disorder such as Alzheimer's Disease or Lewy Body Dementia. The compounds are further useful as diagnostic tools for use in medical or research radiography (e.g., positron emission tomography) when synthesized with a radionuclide (e.g., [18F]. Synthetic schemes to produce such compounds are also provided.</p>
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METHODS OF TREATING ALZHEIMER'S DISEASE (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">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.</p>
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Salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-hepatonic 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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Ligustrazine-fused cyclic compound and medicine composition thereof, as well as application in medicine thereof (Sat, 01 Jul 2017)
The invention discloses a ligustrazine-fused cyclic compound and a medicine composition thereof and application in a medicine. The ligustrazine-fused cyclic compound has the following structural general formula I: as shown in the specification. The medicine composition is a medicinal active component for the ligustrazine-fused cyclic compound and a pharmaceutically acceptable carrier, an excipient, a diluent, an adjuvant, a medium or a combination thereof; the ligustrazine-fused cyclic compound and the medicine composition can be used for preventing or treating cardiovascular and cerebrovascular diseases, digestive system diseases, respiratory diseases, the alzheimer's disease, kidney diseases and complications of the above-mentioned diseases due to thrombus and excessive free radicals. The ligustrazine-fused cyclic compound disclosed by the invention has an extremely good inhibition effect on in vitro ADP (adenosine diphosphate)-induced platelet aggregation; meanwhile, compared with the pharmacokinetic property of ligustrazine serving as a female parent, the pharmacokinetic property of the ligustrazine-fused cyclic compound in the body of a rat is obviously improved.
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APP specific bace inhibitors (asbis) and uses thereof (Sat, 01 Jul 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 ASBI is a flavonoid (e.g. galangin) or flavonoid progrug (e.g., galangin prodrug).
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Amide group substituted hesperetin derivatives, preparation method thereof and application of derivatives as anti-AD (anti-Alzheimer's disease) drugs (Sat, 01 Jul 2017)
The invention belongs to the fields of pharmaceutical chemistry and pharmacotherapeutics and discloses amide group substituted hesperetin derivatives, a preparation method thereof and an application of the derivatives as AD (Alzheimer's disease) treatment drugs. Study proves that the amide group substituted hesperetin derivatives have strong inhibition property and good inhibition selectivity on acetylcholinesterase, and inhibition capacity of the derivatives on acetylcholinesterase is more than 500 times higher than inhibitory activity on butyrylcholinesterase. The study indicates that the compounds can be developed into the AD treatment drugs.
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THERAPEUTIC COMPOUNDS (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The invention provides compounds of formulae I, II, III, and IV:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="145.97mm" wi="62.65mm" file="US20170182046A1-20170629-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers and Alzheimer's disease.</p>
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PIPERIDIN-1 -YL AND AZEPIN-1 -YL CARBOXYLATES AS MUSCARINIC M4 RECEPTOR AGONISTS (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The present invention provides muscarinic M4 receptor agonists of formula (I) and pharmaceutically acceptable salts thereof, wherein m, n, p, q, R, R<sup>2 </sup>and R<sup>3 </sup>are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases such as schizophrenia, Alzheimer's disease and various cognitive disorders as well as in the treatment or alleviation of pain.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.85mm" wi="64.52mm" file="US20170183338A1-20170629-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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Phthalimide IDO1 (indoleamine-2,3-dioxygenase 1) inhibitor and use thereof (Wed, 21 Jun 2017)
The invention relates to the field of medicinal chemistry, in particular to an IDO1 (indoleamine-2,3-dioxygenase 1) inhibitor (I) of a phthalimide structure and a preparation method, wherein X and R are defined in the specification. A pharmacodynamic test shows that the compound can be used for treating diseases with the histopathologic characteristic of an IDO1-mediated tryptophan metabolism pathway, such as malignant tumors, autoimmune diseases, Alzheimer's disease and schizophrenia. (The formula is shown in the specification).
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Heteroaromatic Compounds and their Use as Dopamine D1 Ligands (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">The present invention provides, in part, compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.46mm" wi="69.85mm" file="US20170165270A1-20170615-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) and the uses of such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension. The present invention further provides a D1 agonist with reduced D1R desensitization, a D1 agonist with a reduced β-arrestin recruitment activity relative to Dopamine, a D1 agonist interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, a D1 agonist interacting less strongly the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.</p>
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2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X<sup>1 </sup>and X<sup>2 </sup>are independently, at each occurrence, CR<sup>5 </sup>or N; Y is C<sub>1</sub>-C<sub>6 </sub>alkylene, wherein alkylene is optionally substituted with one to two C<sub>1</sub>-C<sub>3 </sub>alkyl groups; R<sup>1 </sup>is selected from the group consisting of hydrogen, halogen, C<sub>1</sub>-C<sub>6 </sub>alkoxy, —NH<sub>2</sub>, —NHR<sup>6</sup>, —NR<sup>7</sup>R<sup>8 </sup>and —NH—(R<sup>9</sup>)<sub>n</sub>—R<sup>10</sup>, n being 0 or 1; R<sup>2 </sup>is selected from the group consisting of hydrogen, halogen, C<sub>1</sub>-C<sub>6 </sub>alkyl, —NH<sub>2</sub>, —NHR<sup>6</sup>, —NR<sup>7</sup>R<sup>8 </sup>and —NH—(R<sup>9</sup>)<sub>n</sub>—R<sup>10</sup>; R<sup>3 </sup>is selected from the group consisting of hydrogen, hydroxyl, OR<sup>11</sup>, —NR<sup>7</sup>R<sup>8</sup>, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>3</sub>- C<sub>10 </sub>cycloalkyl, C<sub>1</sub>-C<sub>3 </sub>haloalkyl, —C(O)NHR<sup>11</sup>, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R<sup>a </sup>groups; and R<sup>4 </sup>is selected from the group consisting of —NH<sub>2</sub>, —N(R<sup>12</sup>)(V)<sub>p</sub>R<sup>13</sup>, —NH(V)<sub>p</sub>—OR<sup>14</sup>, —NHC(O)R<sup>15</sup>, and groups of formula 1a shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="62.48mm" wi="66.89mm" file="US20170166563A1-20170615-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Heterocyclic flavone derivatives, compositions, and methods related thereto (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as depression, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein.</p>
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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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Hydroxystyrylpyridine mannich bases compound, and preparation method and uses thereof (Wed, 14 Jun 2017)
The invention discloses a novel hydroxystyrylpyridine mannich bases compound (I), and pharmaceutically acceptable salts and a preparation method thereof, a medicine composition, and uses in preparation of a medicine for treating and/or preventing neurodegeneration-related diseases including, but not limited to, vascular dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, progressive lateral sclerosis, neuropathic pain and glaucoma.
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N-(1,2,3,4-tetrahydroisoquinolinyl)-feruloylagmatine-O-alkylamine compound and application (Wed, 14 Jun 2017)
The invention belongs to the technical field of medicinal chemistry and discloses a N-(1,2,3,4-tetrahydroisoquinolinyl)-feruloylagmatine-O-alkylamine compound (I) and pharmaceutically acceptable salt, and a preparation method and application thereof. The structure is as shown in a formula I. The compound (I) provided by the invention has high butyrylcholine esterase inhibiting activity, anti-oxidation activity and Abeta1-42 aggregation inhibiting activity, and has remarkable neuroprotective function on PC12 cell injury induced by hydrogen peroxide, which indicates that the compound is a multi-target-point inhibitor. The compound further shows a good effect of treating alzheimer disease in in-vivo experiments, and has low toxicity and a good clinical application prospect.
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METHOD FOR PREPARING THE ANHYDROUS CRYSTALLINE FORM OF ISONIAZID-DERIVED HYDRAZONE, THUS PRODUCED CRISTALLINE POLYMORPH OF THE ANHYDROUS FORM, USE THEREOF FOR THE TREATMENT OF ALZHEIMER'S DISEASE, PARKINSONISM AND OTHER NEURODEGENERATIVE DISORDERS, AND PHARMACEUTICAL COMPOSITION (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">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.</p>
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Anti-depression Compounds (Fri, 09 Jun 2017)
<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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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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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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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="US09994518-20180612-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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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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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: R<sb>1</sb> is selected from H and CO-NR<sb>8</sb>R<sb>9</sb>, wherein R<sb>8</sb> and R<sb>9</sb> are each independently selected from H, alkyl, cycloalkyl and mono or bicyclic heterocycloalkyl, wherein said alkyl group is optionally substituted by one or more R<sb>12</sb> groups, and said heterocycloalkyl is optionally substituted by R<sb>10</sb> or R<sb>12</sb>; or R<sb>8</sb> and R<sb>9</sb> 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 R<sb>10</sb> and (CH<sb>2</sb>)<sb>m</sb>R<sb>12</sb>; R<sb>2</sb> is selected from H and alkyl, wherein said alkyl group is optionally substituted by one or more R<sb>12</sb> groups; R<sb>3</sb> is selected from alkyl, cycloalkyl and heterocycloalkyl, each of which may be optionally substituted by halo, OH or alkoxy; Z<sb>1</sb>, Z<sb>2</sb>, Z<sb>3</sb> and Z<sb>4</sb> are all C; R<sb>4</sb>, R<sb>5</sb>, R<sb>6</sb> and R<sb>7</sb> are each independently selected from H, alkyl, CN, NO<sb>2</sb>,OH, alkoxy, NHCO-alkyl, halo and haloalkyl; or Ζ<sb>1</sb>, Z<sb>3</sb> and Z<sb>4 </sb>are ail C, Z<sb>2</sb> is N, R<sb>5</sb> is absent and R<sb>4</sb>, R<sb>6</sb> and R<sb>7</sb> are as defined above; or Z<sb>1</sb>, Z<sb>3</sb> and Z<sb>4</sb> are all C, Z<sb>1</sb> is N, R<sb>4</sb> is absent and R<sb>5</sb>, R<sb>6</sb> and R<sb>7</sb> are as defined above; each R<sb>10</sb> and R11 is independently alkyl; each R<sb>12</sb> is independently selected from CO<sb>2</sb>R<sb>10</sb>, COOH, OH, alkoxy, haloalkyl, NH<sb>2</sb>, NHR<sb>10</sb>, NR<sb>10</sb>R<sb>11</sb>, heteroaryl and heterocycloalkyl; R<sb>13</sb> 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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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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6-amino-5,6,7,8-tetrahydronaphthalen-2-yl or 3-aminochroman-7-yl derivatives as taar modulators (Thu, 25 May 2017)
The present invention relates to a compound of formula (I), wherein L is -C(O)NH-, -NHC(O)-, -S(O)2NH-, -NH- or -NHC(O)NH-; Ar is phenyl, benzyl, naphthyl or heteroaryl, selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, isoxazolyl or pyrazinyl, wherein Ar may be optionally substituted by one, two or three R1; R1 is hydrogen, lower alkyl, lower alkoxy, halogen, cyano, cycloalkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen, or is phenyl optionally substituted by one or two halogen atoms, CF3O or lower alkyl, or is furanyl, thiazolyl or thiophenyl, optionally substituted by halogen or lower alkyl; X is CH or O; R is hydrogen or halogen; or a pharmaceutically suitable acid addition salt thereof, all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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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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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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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="US10017508-20180710-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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Pyridyl-triazabicycles (Thu, 11 May 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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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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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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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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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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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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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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Synthesis method of diagnosis and treatment integrated target prodrug for AD (Alzheimer's disease) tau protein (Thu, 27 Apr 2017)
As an indole drug, T807 is widely applied to a PET tracer agent of AD due to the characteristics of high selectivity and affinity of combination with tau protein, good biological distribution in animal bodies, less retention in white matter, stable uptake in brains, removal fastness and the like. The invention discloses a synthesis method of a diagnosis and treatment integrated target prodrug, namely, amino-T807, for AD (Alzheimer's disease) tau protein. Boc-protected nitro-T807 is prepared from 4-bormophenylboronic acid, 3-bromo-4-nitropyridine and 3-bromo-6-nitropyridine used as raw materials through several steps of coupling reactions, and after nitrogen reduction, amino-T807 is obtained through deprotection of Boc. Raw materials used in the route are cheap and available the reaction conditions are mild, the yield is higher, and the environmental pollution is smaller.
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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 (Thu, 27 Apr 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-HT4 receptor ligand intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.
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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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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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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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Oxadiazole derivative, preparing method of oxadiazole derivative and application of oxadiazole derivative to medicines (Thu, 20 Apr 2017)
The invention relates to an oxadiazole derivative, a preparing method of the oxadiazole derivative and application of the oxadiazole derivative to medicines, in particular to an oxadiazole derivative shown in the general formula (1), a preparing method of the oxadiazole derivative, a medicine composition comprising the derivative and application of the oxadiazole derivative to treatment of diseases with the tryptophan metabolic pathway pathological feature mediated by IDO. The diseases include the cancer, the alzheimer disease, the autoimmune disease, the depression, the anxiety disorder, the cataract, the psychological disorder and the AIDS. Definition of substituent groups in the general formula (1) is the same with the definition of the substituent groups in the specification.
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DUAL INHIBITOR COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISORDERS AND ALZHEIMER'S DISEASE (Thu, 20 Apr 2017)
The present invention relates to Compounds of Formula (I) and pharmaceutical compositions containing the same. It further relates to their use in the prevention or treatment of central nervous system diseases or disorders, in particular, cognitive, neurodegenerative or neuronal diseases or disorders.
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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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ORGANOSULFUR COMPOUNDS FOR THE PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 14 Apr 2017)
<p id="p-0001" num="0000">Divalent salts of S-allylmercapto-N-acetylcysteine and related compositions are disclosed which can be administered in order to provide protection from the formation of aldehyde-protein adducts, protein carbonylation, protein aggregation, 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, stroke and cerebral ischemia.</p>
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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="39.71mm" wi="53.17mm" file="US09662316-20170530-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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UREA COMPOUNDS AND THEIR USE AS ENZYME INHIBITORS (Fri, 14 Apr 2017)
<p id="p-0001" num="0000">A compound having the following structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="58.34mm" wi="60.45mm" file="US20170101381A1-20170413-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt or derivative thereof. The compound may be used in the treatment or prevention of a disorder selected from appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions such as opiates, nicotine, cocaine, alcohol and psychostimulants, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease such as hepatitis and liver cirrhosis, arthritis and osteoporosis.</p>
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Substituted prolines/piperidines as orexin receptor antagonists (Fri, 14 Apr 2017)
<p id="p-0001" num="0000">The present invention is directed to compounds that modulate the bioactivity of an orexin receptor such as OX<sub>1 </sub>or OX<sub>2</sub>, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention. For example, orexin receptor-modulatory compounds of the present invention can be used in treatment of an eating disorder, obesity, alcoholism or an alcohol-related disorder, drug abuse or addiction including addiction to cocaine, opiates, amphetamines, or nicotine, a sleep disorder, a cognitive dysfunction in a psychiatric or neurologic disorder, depression, anxiety, panic disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, headache, migraine, pain, gastrointestinal diseases, epilepsy, inflammations, immune-related diseases, endocrine-related diseases, cancer, hypertension, behavior disorder, mood disorder, manic depression, dementia, sex disorder, psychosexual disorder, or renal disease.</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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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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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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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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Magnetic platform for direct and multiplex immune-based detection of trace amount of protein biomarkers (Fri, 07 Apr 2017)
<p id="p-0001" num="0000">The present invention discloses a magnetic platform for direct and multiplex immune-based detection of trace amount of protein biomarkers for cancers, neurodegenerative disease such as Alzheimer's disease</p>
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Aromatic heterocyclic derivatives and pharmaceutical applications thereof (Fri, 07 Apr 2017)
<p id="p-0001" num="0000">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<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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Dual inhibitor compounds for use in the treatment of neurodegenerative disorders and alzheimer's disease (Fri, 07 Apr 2017)
<p id="p-0001" num="0000">The present invention relates to Compounds of Formula (I) and pharmaceutical compositions containing the same. It further relates to their use in the prevention or treatment of central nervous system diseases or disorders, in particular, cognitive, neurodegenerative or neuronal diseases or disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.73mm" wi="60.11mm" file="US09975861-20180522-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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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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5-OXA-2-AZABICYCLO[2.2.2]OCTAN-4-YL AND 5-OXA-2-AZABICYCLO[2.2.1]HEPTAN-4-YL DERIVATIVES AS TAAR1 MODULATORS (Thu, 06 Apr 2017)
The invention relates to compounds of formula (I) wherein.....C.....is -CH<sb>2</sb>- or -CH<sb>2</sb>-CH<sb>2</sb>-; X is -NH-, -C(0)NH- or -NHC(0)NH-; Ar is phenyl or a 5 or 6-membered heteroaryl group containing one or two N atoms; R<sp>1</sp> is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by cycloalkyl, lower alkoxy substituted by halogen or is cycloalkyl; -( )- is -CH<sb>2</sb>-; n is 0 or 1; m is 0, 1 or 2; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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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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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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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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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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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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