Parkinson's disease

SUBSTITUTED INDAZOLE OR INDOLE DERIVATIVES AS IN VITRO MAO-B INHIBITORS (Fri, 18 Jul 2014)
Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson's disease, Alzheimer's disase and dementia
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(4E)-4-(4-SUBSTITUTED BENZYLIDENEAMINO)-2,3-DIHYDRO-3- SUBSTITUTED-2-THIOXOTHIAZOLE-5-CARBONITRILES AS A2AR ANTAGONIST AND PROCESS FOR PREPARATION THEREOF (Fri, 11 Jul 2014)
The present, invention relates to novel the (4E)-4-(4-substituted benzylideneamino)- 2,3-dihydro-3-substituted -2-thioxothiazole-5-carbonitriles of general formula A and a process for the preparation thereof. The compounds of present invention are useful in the treatment of central nervous disorders including, Parkinson disease, Huntington's disease, attention disorder, cognition, Alzheimer disease, depression and hypertension.
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AMINOPYRIDINE DERIVED COMPOUNDS AS LRRK2 INHIBITORS (Fri, 11 Jul 2014)
The present invention is directed to aminopyridine derived compounds of formula (A). The compounds are considered useful for the treatment of diseases associated with LRRK2 such a Lewy body dementia, Parkinson's disease or cancer.
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COMT INHIBITORS (Fri, 04 Jul 2014)
The present invention relates to compounds of formula (I), wherein the substituents are described in claim 1 and to the pharmaceutically acceptable salts thereof. These compounds inhibit the enzyme catechol-O-methyltransferase (COMT). The compounds may be used for the treatment of Parkinson's disease, depression, cognitive impairment and motor symptoms, resistant depression, cognitive impairment, mood and negative symptoms of schizophrenia.
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DEUTERIUM SUBSTITUTED FUMARATE DERIVATIVES (Fri, 27 Jun 2014)
Provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof. Also provided is a method of treating, prophylaxis, or amelioration of a disease, comprising administering to a subject in need of treatment for the disease an effective amount of a compound of formula (I) described herein. In one embodiment, the method is a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, or Alzheimer's disease.
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8'-HYDROXY-DIHYDROERGOTAMINE COMPOUNDS AND COMPOSITIONS (Fri, 27 Jun 2014)
8'-HydiOxy-Dihydroergotamine (8'-OH DHE) medicinal compounds, compositions, and dosage forms containing such compositions are provided. Also provided herein are methods of treatment, prevention, or amelioration of diseases, conditions or disorders selected from amyotrophic lateral sclerosis (ALS), Parkinson's disease, stress/anxiety, nausea, emesis, aggression, pain, neuropathic pain, sleeplessness, insomnia, restless leg syndrome and depression using the compounds, compositions, dosage forms and administration techniques disclosed herein.
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NOVEL METHYSERGIDE DERIVATIVES (Fri, 27 Jun 2014)
Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT2B receptor without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT1A receptor using the compounds and compositions disclosed herein.
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OXAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH (Fri, 20 Jun 2014)
<p id="p-0001" num="0000">The present invention is directed to certain oxazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.</p>
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SUBSTITUTED HETEROCYCLIC DERIVATIVES (Sat, 31 May 2014)
The present invention relates to compounds of general formula (I-1) or (I-2) wherein R1 is hydrogen, lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; R1' is hydrogen, lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; with the proviso that both R1 and R1' may be simultaneously hydrogen, but only one of R1 and R1' is lower alkyl, lower alkoxy, halogen, O(CH2)2-lower akoxy, O(CH2)2N(CH3)2, or O(CH2)-morpholinyl; Het is a 5-or 6 membered heteroaryl group, wherein the heteroatom is selected from N, O or S; X is -CRR'-, -CRR'-NR'-, -C(O)-, -CH2-S-, -CH2-S(O)2-, CH2-O- or -CH2-CRR'-; R/R' are independently from each other hydrogen, lower alkyl, hydroxy or phenyl, or R and R' may form together with the carbon atom to which they are attached a cyclopropyl ring; R2 is lower alkyl, -C(O)O-lower alkyl, C3-6-cycloalkyl optionally substituted by lower alkyl or =O, bridged cyclohexyl or C3-6-cycloalkenyl, or is a 5-membered heteroaryl group, wherein the heteroatom is selected from N, O or S and which is optionally substituted by one or more lower alkyl, or is pyridinyl, optionally substituted by halogen or lower alkoxy; or is phenyl, optionally substituted by one or more R2', selected from halogen, cyano, S(O)2-lower alkyl, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or amino, or is benzo[1,3]dioxolyl, naphthyl, indolyl, benzo-isoxazolyl, 2,3-dihydro-1H-indenyl, optionally substituted by lower alkoxy or by an oxo group, or is 3,4-dihydro-2H- [1,4]oxazinyl, optionally substituted by an oxo group, or is a five or six membered heterocycloalkyl group; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment or prophylaxis of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.
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THERAPEUTIC AGENTS USEFUL FOR TREATING PAIN (Fri, 23 May 2014)
<p id="p-0001" num="0000">A compound of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="18.71mm" file="US20140142112A1-20140522-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Ar<sub>1</sub>, A, R<sub>3</sub>, X, and m are as disclosed herein and Ar<sub>2 </sub>is a benzothiazolyl, benzooxazolyl, or benzoimidazolyl group or a pharmaceutically acceptable salt thereof (a “Benzoazolylpiperazine Compound”), compositions comprising a Benzoazolylpiperazine Compound, and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound are disclosed.</p>
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ERGOLINE DERIVATIVES AS DOPAMINE RECEPTOR MODULATORS (Fri, 23 May 2014)
The invention provides compounds of formula (I) wherein R1-R4 have any of the values defined in the specification, and salts thereof. The compounds are useful as dopamine receptor modulators for the treatment of diseases where modulation of dopamine receptors is implicated (e.g. sexual dysfunction, prolactinoma, Parkinson's disease, and Cushings disease).
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HETEROAROMATIC COMPOUNDS AS DOPAMINE D1 LIGANDS (Fri, 16 May 2014)
The present invention provides, in part, compounds of Formula I and pharmaceutically acceptable salts thereof and N-oxides of the foregoing; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, salts or N-oxides, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCI, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, and bipolar disorder.
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HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS (Fri, 09 May 2014)
<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="61.64mm" file="US20140128374A1-20140508-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 of the foregoing; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, salts or N-oxides, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, impulsivity, compulsive gambling, overeating, autism spectrum disorder, MCI, age-related cognitive decline, dementia, RLS, Parkinson's disease, Huntington's chorea, anxiety, depression, MDD, TRD, and bipolar disorder.</p>
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7,8-DIHYDOXYFLAVONE AND 7,8-SUBSTITUTED FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO (Fri, 09 May 2014)
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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USE OF A BIOACTIVATED PHYTOCHEMICAL AS A NEUROPROTECTIVE AGENT FOR PREVENTING AND TREATING DISORDERS RELATED TO NERVOUS SYSTEM (Fri, 25 Apr 2014)
The use of a bioactivated phytochemical is disclosed for preventing and treating neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis. In particular, said bioactivated phytochemical is Rs-Glucoraphanin bioactivated with myrosinase and has proved to be particularly suitable as being surprisingly effective and extremely well tolerated by the body.
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Fri, 18 Apr 2014)
<p id="p-0001" num="0000">Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.</p>
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ARYLVINYLAZACYCLOALKANE COMPOUNDS AND METHODS OF PREPARATION AND USE THEREOF (Fri, 18 Apr 2014)
<p id="p-0001" num="0000">Novel vinylazacycloalkane compounds of Formula (I) are disclosed. The compounds are ligands of various nAChRs. The compounds and their pharmaceutically acceptable salts can be used to prepare pharmaceutical compositions and/or medicaments intended to prevent or treat disorders associated with dysfunction of nAChRs, especially within the central nervous system or the gastrointestinal system. Examples of types of disorders that can be treated include neurodegenerative disorders, including central nervous system disorders such as Alzheimer's disease, cognitive disorders, motor disorders such as Parkinson's disease, drug addiction, behavioral disorders and inflammatory disorders within the gastrointestinal system. The compounds can also serve as analgesics in the treatment of acute, chronic or recurrent pain.</p>
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ACYLPIPERAZINES AS INHIBITORS OF TRANSGLUTAMINASE AND THEIR USE IN MEDICINE (Fri, 18 Apr 2014)
The present invention relates to novel compounds of Formula I capable of inhibiting tissue transglutaminase, and uses of the same in medicine. In particular, the invention provides compounds for use in the treatment of prevention of disease and conditions such as fibrosis (e.g. cystic fibrosis), scarring, neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease and Parkinson's disease), autoimmune diseases (e.g. multiple sclerosis and coeliac disease), thrombosis, proliferative disorders (e.g. cancers), AIDS, psoriasis and inflammation (e.g. chronic inflammatory diseases).
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HEXAHYDRODIBENZO[A,G]QUINOLIZINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION AND USE THEREOF (Thu, 10 Apr 2014)
The present invention relates to a novel hexahydrodibenzo[a,g]quinoline compound represented by general formula (I) and its derivatives, enantiomer, diastereoisomer, raceme and mixtures thereof, as well as pharmaceutically acceptable salts thereof. The present invention further relates to a method for preparing the compound, and the compound has good prevention and treatment effect on neurological diseases, especially diseases associated with dopamine receptor and 5-hydroxytryptamine receptor. The bioactivity experiment demonstrates that, the compound is expected to be developed into a novel and potent chemical entity for treating diseases associated with dopamine receptor and 5-hydroxytryptamine receptor, especially schizophrenia, Parkinson's disease, drug addiction, migraine and so on.
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URIDINE DIPHOSPHATE DERIVATIVES, PRODRUGS, COMPOSITIONS AND USES THEREOF (Fri, 04 Apr 2014)
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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HEXAHYDRODIBENZO[A,G]QUINOLIZINE COMPOUND, PREPARATION METHOD THEREOF, PHARMACEUTICAL COMPOSITION AND USE THEREOF (Fri, 28 Mar 2014)
<p id="p-0001" num="0000">The present invention relates to a novel hexahydrodibenzo[a,g]quinoline compound represented by general formula (I) and its derivatives, enantiomer, diastereoisomer, raceme and mixtures thereof, as well as pharmaceutically acceptable salts thereof. The present invention further relates to a method for preparing the compound, and the compound has good prevention and treatment effect on neurological diseases, especially diseases associated with dopamine receptor and 5-hydroxytryptamine receptor. The bioactivity experiment demonstrates that, the compound is expected to be developed into a novel and potent chemical entity for treating diseases associated with dopamine receptor and 5-hydroxytryptamine receptor, especially schizophrenia, Parkinson's disease, drug addiction, migraine and so on.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.12mm" wi="60.79mm" file="US20140088130A1-20140327-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLIC COMPOUNDS AND THEIR USE FOR THE TREATMENT OF NEURODEGENERATIVE TAUOPATHIES (Fri, 28 Mar 2014)
The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.
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FTO MODULATING COMPOUNDS AND METHODS OF USE (Fri, 28 Mar 2014)
The present invention relates to compounds which modulate the level or activity of polypeptides having Fe(II) and 2-oxoglutarate (2QG)-dependent oxygenase activity in a cell, tissue, or subject, exemplified by the Fat Mass and Obesity Associated protein (FTO). Aspects relate to N-(3,4-dihydroxy-5-aryl-2-furanyl)-sulfonamides, methods for their synthesis, and methods of using these compounds to modulate the activity of FTO in a cell-free sample, a cell-based assay, and in a subject. Aspects are also directed to compositions comprising compounds which modulate the activity of FTO, including pharmaceutically-acceptable compositions, and to methods of preventing, ameliorating, or treating FTO-mediated conditions or diseases in a subject, including stroke, epilepsy, depression, and degenerative central nervous system disorders such as Alzheimer's and Parkinson's disease. Other aspects elate to use of the compounds to ameliorate or treat conditions associated with metabolic disorders, such as diabetes and obesity.
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Novel Compositions for Preventing and/or Treating Degenerative Disorders of the Central Nervous System (Fri, 21 Mar 2014)
<p id="p-0001" num="0000">The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.</p>
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B- AND y -DIKETONES AND y -HYDROXYKETONES AS WNT/ B -CATENIN SIGNALING PATHWAY ACTIVATORS (Fri, 21 Mar 2014)
<p id="p-0001" num="0000">The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones 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 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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TRIAZOLE CARBOXAMIDE DERIVATIVES (Fri, 21 Mar 2014)
The invention relates to compounds of formula (I), wherein R1 is phenyl or pyridinyl, optionally substituted by halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen and lower alkoxy substituted by halogen; X1 is -N= or CH; X2 is CR2 or =N-; X3 is -N= or CH; with the proviso that only two of X1, X2 or X3 are nitrogen; wherein is a triazole group, selected from R2 is hydrogen or lower alkyl; Z is a bond, -O- or -CH2-; or to pharmaceutically suitable acid addition salts thereof. It has now been found that the compounds of formulas I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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Methods and Compositions for Treating Parkinson's Disease (Fri, 07 Mar 2014)
<p id="p-0001" num="0000">The invention discloses methods and compositions for treating or preventing Parkinson's disease by administering a compound of Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.85mm" wi="36.24mm" file="US20140066434A1-20140306-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PRO-NEUROGENIC COMPOUNDS (Fri, 28 Feb 2014)
This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.
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PRO-NEUROGENIC COMPOUNDS (Fri, 28 Feb 2014)
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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Morpholinoalkyl Fumarate Compounds, Pharmaceutical Compositions, and Methods of Use (Fri, 21 Feb 2014)
<p id="p-0001" num="0000">Morpholinoalkyl fumarates, pharmaceutical compositions comprising the morpholinoalkyl fumarates, and methods of using morpholinoalkyl fumarates and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 14 Feb 2014)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, or forms thereof are active on Fms protein kinase, or on Fms and Kit protein kinase, or on Fms and Flt-3 protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinase, Kit protein kinase, or Flt-3 protein kinase including rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, acute myeloid leukemia, melanoma, multiple myeloma, metastatic breast cancer, prostate cancer, pancreatic cancer, neurofibromatosis, brain metastases, and gastrointestinal stromal tumors.</p>
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Selective Cysteine Protease Inhibitors and Uses Thereof (Fri, 07 Feb 2014)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease).</p>
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COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES SUCH AS ALZHEIMER'S DISEASE, TYPE 2 DIABETES, AND PARKINSON'S DISEASE (Fri, 07 Feb 2014)
<p id="p-0001" num="0000">Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.</p>
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Camsylate Salt (Fri, 31 Jan 2014)
<p id="p-0001" num="0000">A camsylate salt of (1r,1′R,4R)-4-methoxy-5″-methyl-6′-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3′H-dispiro[cyclohexane-1,2′-inden-1′2′-imidazole]-4″-amine, pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating Aβ-related pathologies such as Alzheimer's Disease, Down's syndrome, β-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.</p>
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UREA COMPOUNDS AND THEIR USE AS ENZYME INHIBITORS (Fri, 31 Jan 2014)
A compound having the following structure: 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.
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HETEROCYCLIC FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO (Fri, 31 Jan 2014)
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 5 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 to a subject in need thereof.
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DI-AND TRI-HETEROARYL DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 24 Jan 2014)
The present invention relates to certain di- and tri-heteroaryl derivatives, 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, and multiple system atrophy.
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BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 24 Jan 2014)
Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M1, M2, M3, M4, M5) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. This bitopic ligand and its structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M1-M5 acetylcholine receptors.
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BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 17 Jan 2014)
<p id="p-0001" num="0000">Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M<sub>1</sub>, M<sub>2</sub>, M<sub>3</sub>, M<sub>4</sub>, M<sub>5</sub>) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. This bitopic ligand and its structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M<sub>1</sub>-M<sub>5 </sub>acetylcholine receptors.</p>
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ARYLSULFONYL PYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS (Fri, 10 Jan 2014)
<p id="p-0001" num="0000">This invention concerns arylsulfonyl pyrazoline carboxamidine 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 parkinson's disease, huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, irritable bowel syndrome, obesity and type-2 diabetes. The compounds have the general formula (1) wherein the symbols have the meanings given in the description.</p>
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NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS (Sat, 04 Jan 2014)
The present invention provides novel 4,5-disubstituted-7H-pyrrolo[2,3- c/]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4 and R5 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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Novel 4-(Substituted Amino)-7H-Pyrrolo[2,3-d] Pyrimidines As LRRK2 Inhibitors (Fri, 03 Jan 2014)
<p id="p-0001" num="0000">The present invention provides novel 4,5-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.74mm" wi="54.53mm" file="US20140005183A1-20140102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.</p>
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6,7-DIHYDRO-PYRAZOLO[1,5-a]PYRAZIN-4-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 03 Jan 2014)
<p id="p-0001" num="0000">The present invention relates to novel 6,7-dihydro-pyrazolo[1,5-a]pyrazin-4-yl-amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.</p>
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B- AND Y -DIKETONES AND Y -HYDROXYKETONES AS WNT/ B -CATENIN SIGNALING PATHWAY ACTIVATORS (Fri, 03 Jan 2014)
<p id="p-0001" num="0000">The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones 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 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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GLYCINE TRANSPORT INHIBITOR (Thu, 02 Jan 2014)
The present invention relates to novel compounds of formula [I] or pharmaceutically acceptable salts thereof: The compounds of the present invention are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.
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NOVEL CABERGOLINE DERIVATIVES (Sat, 28 Dec 2013)
Provided herein are novel cabergoline analogs and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing dopaminergic D2 receptors and/or antagonizing or inhibiting activity of receptors such as the 5-HT2 serotonin receptors using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTID and/or the 5-HTIB receptor, without agonizing (or very weakly agonising) the 5-HT2B receptor using the compounds and compositions disclosed herein.
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CYCLOHEXANE-1,2'-NAPHTHALENE-1',2"-IMIDAZOLE COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Sat, 28 Dec 2013)
Cyclohexane-1,2'-naphthalene-1',2''-imidazole compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, 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, methods of therapy using such compounds, and pharmaceutical compositions containing such compounds.
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CAMSYLATE SALT (Sat, 28 Dec 2013)
A camsylate salt of (1r,1 'R,4R)- 4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3'H-dispiro[cyclohexane-1,2'-inden-1'2'-imidazole]-4"-amine, pharmaceutical compositions containing the salt and therapeutic uses of the salt for treating Αβ-related pathologies such as Alzheimer's Disease, Down's syndrome, β-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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CYCLOHEXANE-1,2'-INDENE-1',2"-IMIDAZOL COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Sat, 28 Dec 2013)
Cyclohexane-1,2'-indene-1',2''-imidazole compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, 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, methods of therapy using such compounds, and pharmaceutical compositions containing such compounds.
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CYCLOALKYL ETHER COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Sat, 28 Dec 2013)
Cycloalkyl ether compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Αβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, 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 and pharmaceutical compositions containing such compounds. Formula (I) wherein A is -O-, or -CH2-, n is 0 or 1.
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2H-IMIDAZOL-4-AMINE COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Sat, 28 Dec 2013)
2H-imidazol-4-amine compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Αβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, 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 methods of therapy, and pharmaceutical compositions containing such compounds. Formula (I) wherein A is -O- or -CH2-, n is 1 or 1.
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INHIBITORS OF POLO-LIKE KINASE (Fri, 13 Dec 2013)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="55.29mm" file="US20130331376A1-20131212-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, E<sup>1</sup>, E<sup>2</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.</p>
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SPECIFIC DIARYLHYDANTOIN AND DIARYLTHIOHYDANTOIN COMPOUNDS (Fri, 13 Dec 2013)
<p id="p-0001" num="0000">Compositions, such as pharmaceutical compositions, comprising specific diarylhydantoin and diarylthiohydantoin compounds, or salts or solvates thereof, are provided. Isolated and purified forms of the compounds are also described, as are unit dosage forms, compositions of substantially pure compound and kits comprising the compounds. The compounds and pharmaceutical compositions thereof may find use in the prevention and/or treatment of a variety of conditions, including prostate cancer, Parkinson's disease, Alzheimer's disease, and others.</p>
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GLYCINE TRANSPORTER-INHIBITING SUBSTANCES (Fri, 13 Dec 2013)
<p id="p-0001" num="0000">The present invention relates to novel compounds of formula [I] or pharmaceutically acceptable salts thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.92mm" wi="68.24mm" file="US20130331571A1-20131212-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds of the present invention are useful in the prevention or treatment of diseases such as schizophrenia, Alzheimer's disease, cognitive impairment, dementia, anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, post-traumatic stress disorder, specific phobias, acute stress disorder), depression, drug dependence, spasm, tremor, pain, Parkinson's disease, attention deficit hyperactivity disorder, bipolar disorder, eating disorder, or sleep disorders, which is based on the glycine uptake-inhibiting action.</p>
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METHODS FOR TREATING NEUROLOGICAL DISEASE (Fri, 06 Dec 2013)
<p id="p-0001" num="0000">Neurological disorders and diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Down's syndrome, can be ameliorated or beneficially treated by administration of a formulation comprising an effective amount of a pyrone-indole derivative of formula (I)</p> <p id="p-0002" num="0000"> <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>Ar—B—Ar′  (I)<?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0003" num="0000">wherein AR represents an indole nucleus ring system:</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.05mm" wi="27.69mm" file="US20130324583A1-20131205-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">Ar′ represents an alpha-, beta- or gamma-pyrone nucleus ring system:</p> <p id="p-0006" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="21.76mm" wi="69.26mm" file="US20130324583A1-20131205-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0007" num="0000">and each of B, R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>1</sub>′ and R<sub>2</sub>′ are as defined herein.</p>
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METHOD OF PRODUCING BIPHENOLIC COMPOUND, NOVEL BIPHENYL COMPOUND AND SYNTHESIS METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR TREATING PARKINSON'S DISEASE (Fri, 15 Nov 2013)
<p id="p-0001" num="0000">A method of producing honokiol and analogues thereof, and novel intermediates prepared by virtue thereof are disclosed herein. A pharmaceutical composition for treating Parkinson's disease, which contains honokiol and/or the analogues thereof, is also disclosed herein.</p>
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HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF (Fri, 15 Nov 2013)
Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and neurological disorders, including, but not limited to, e.g., psychosis, schizophrenia, depression, movement disorders, and Parkinson's disease.
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LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Fri, 08 Nov 2013)
<p id="p-0001" num="0000">Disclosed are compounds of Formula (I): and the pharmaceutically acceptable salts thereof, wherein “A” is S—; —SO—, —SO<sub>2</sub>—, —O— or NR<sup>ac</sup>—, wherein Rac is H, or C<sub>1-20 </sub>alkyl and R<sup>1 </sup>through R<sup>5 </sup>are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="54.78mm" file="US20130296317A1-20131107-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE (Fri, 08 Nov 2013)
Compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3 and A are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 08 Nov 2013)
Pyrazole compounds that are modulators of LRRK2, methods of making the compounds, and methods for using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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TRIAZOLOPYRIDAZINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF (Fri, 08 Nov 2013)
The present invention provides novel LRRK2 kinase inhibitors and methods of treating disease states using these inhibitors. Certain triazolopyridazine compounds have been discovered according to the present disclosure that inhibit LRRK2, and therefore find utility in the treatment of a number of disorders neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy.
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DUAL TARGETING COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE (Fri, 01 Nov 2013)
Compounds of formula (I) wherein the groups are as defined in the description, are used as medicaments, in particular for the treatment of a disease selected from the group consisting of: cognitive impairment, memory dysfunction, neurodegenerative disorders and related dementia, Alzheimer's disease, Parkinson's disease, neuropsychiatric behavior associated with Alzheimer's disease, pain, depression, attention deficit hyperactivity disorder and for pharmacological addictive substance or intoxicant therapy; and for the neuroprotection from NMDA toxicity.
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METHOD FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISORDER BY USING DIFFUSION KURTOSIS IMAGING (Fri, 25 Oct 2013)
<p id="p-0001" num="0000">The invention relates to the use of diffusion kurtosis imaging (DKI) in the diagnosis of Parkinson Disease related neurodegenerative disorders, including (but not limited to) Parkinson's disease (PD) and Parkinson plus syndromes.</p>
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NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS (Fri, 25 Oct 2013)
<p id="p-0001" num="0000">The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula (I). Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine for agonists.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.27mm" wi="60.03mm" file="US20130281482A1-20131024-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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5,6-DIHYDRO-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 18 Oct 2013)
<p id="p-0001" num="0000">The present invention relates to novel 5,6-dihydro-imidazo[1,2-a]pyrazin-8-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebrovascular amyloid angiopathy, multi-infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.</p>
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PARKINSON'S DISEASE BIOMARKER (Fri, 18 Oct 2013)
The present invention relates to a biomarker for Parkinson's disease. The biomarker and products associated with the biomarker may be used to assist diagnosis or to assess onset and/or development of Parkinson's disease. The invention also relates to use of the biomarker in clinical screening, assessment of prognosis, evaluation of drug treatments, drug screening or drug development in the field of Parkinson's disease and Parkinson's disease related disorders.
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TREATMENT OF MITOCHONDRIAL DISEASES (Fri, 11 Oct 2013)
<p id="p-0001" num="0000">The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.</p>
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NOVEL COMPOUND AND MEDICAL USE THEREOF (Thu, 10 Oct 2013)
Provided is a levodopa prodrug that overcomes the problems attributed to the blood kinetics of levodopa such as large number of doses and the incidence of side effects due to frequent dosing. (2S)-2-Amino-3-(3,4-bis((2-(benzoyloxy)-2-methylpropanoyl)oxy)phenyl)propanoic acid, a salt thereof, or a solvate thereof is a levodopa prodrug, and provides a flat blood concentration-time profile of levodopa through oral administration, and therefore is useful as a preventive and/or therapeutic agent for Parkinson's disease and/or Parkinson's syndrome that overcomes the problems associated with pharmaceutical preparations of levodopa.
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TRANSMUCOSAL DELIVERY OF ENGINEERED POLYPEPTIDES (Fri, 04 Oct 2013)
Formulations are provided that comprise compounds having inter alia good duration of action, high potency and/or convenient dosing regimens, and a permeation enhancer for transmucosal administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. The pharmaceutical compositions provided are suitable for methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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ENGINEERED POLYPEPTIDES (Fri, 04 Oct 2013)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens. The compounds are engineered polypeptides which incorporate an exendin domain in combination with a humanized chimeric seal leptin. Also provided are pharmaceutical compositions and methods of treatment for diseases including diabetes, overweight, obesity, Alzheimer's disease, short bowel syndrome, fatty liver disease, dyslipidemia, coronary artery disease, stroke, hyperlipidemia, NASH or Parkinson's disease.
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SALICYLIC ACID DERIVATIVES USEFUL AS GLUCOCEREBROSIDASE ACTIVATORS (Fri, 04 Oct 2013)
Compounds of Formula (I) and the pharmaceutically acceptable salts thereof are disclosed. The variables. R1-R13, m, n, o, and p are disclosed herein. The compounds are useful for treating Gaucher disease and inhibiting the onset of Gaucher disease symptoms in a patient having a GBA gene mutation and for treating Parkinson's disease. Pharmaceutical compositions containing compounds of Formula (I) and methods of treatment comprising administering compounds of Formula (I) are also disclosed.
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PHENYL-UREA AND PHENYL-CARBAMATE DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 04 Oct 2013)
The present invention relates to certain phenyl-urea and phenyl-carbamate derivatives, 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, and multiple system atrophy.
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NOVEL FLUORINATED SULFAMIDES EXHIBITING NEUROPROTECTIVE ACTION AND THEIR METHOD OF USE (Fri, 27 Sep 2013)
<p id="p-0001" num="0000">Pharmaceutical compositions of the invention include fluorinated sulfamide derivatives having a disease-modifying action in the treatment of diseases associated with excitotoxicity and accompanying oxidative stress that include epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, heavy metal toxicity and any neurodegenerative disease involving glutamate toxicity.</p>
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Continuous Administration of Levodopa and/or Dopa Decarboxylase Inhibitors and Compositions for Same (Fri, 27 Sep 2013)
<p id="p-0001" num="0000">Disclosed herein are for example, liquid aqueous compositions that include for example an ester or salt of levodopa, or an ester or salt of carbidopa, and methods for treating neurological or movement diseases or disorders such as restless leg syndrome, Parkinson's disease, secondary parkinsonism, Huntington's disease, Parkinson's like syndrome, PSP, MSA, ALS, Shy-Drager syndrome, dystonia, and conditions resulting from brain injury including carbon monoxide or manganese intoxication, using substantially continuous administration of levodopa and/or carbidopa or ester and/or salt thereof.</p>
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PYRAZOLOPYRIDINES FOR TREATMENT OF PARKINSONS DISEASE (Fri, 27 Sep 2013)
The invention relates to a compound of formula (1A) or (1B), or a pharmaceutically acceptable salt thereof, Wherein R1 is a group selected from alkyl, monocyclic heterocycloalkyl, bicyclic heterocycloalkyl and cycloalkyl, each of which is optionally substituted by one or more groups selected from alkyl, halo and cycloalkyl; for formula (1A): one, two or three of X1, X2, X3 and X4 are N, and the remainder are each independently CR2; or for formula (1B): X4 is C or N; and one or two of X1, X2and X3 are independently selected from N and NR8, and the remainder are each independently CR2; such that X1, X2,X3,X4and N form a heteroaryl group; each R2 is independently selected from H, alkyl, CN, halo, heteroaryl, heterocycloalkyl, cycloalkyl, OR4, CONR5R6 and SO2R7, wherein said alkyl, heteroaryl, heterocycloalkyl and cycloalkyl groups are each optionally further substituted by one or more groups selected from alkyl, halo and OR9; each R8 is independently selected from H and alkyl, wherein said alkyl group is optionally further substituted by one or more groups selected from CN, halo, heteroaryl, heterocycloalkyl, cycloalkyl, OR4, CONR5R6 and SO2R7; R4, R5, R6, R7and R9 are each independently selected from H and alkyl; or R5 and R6 together with the nitrogen to which they are attached are linked to form a cyclic group which optionally further comprises one or more heteroatoms selected from O, N and S; with the proviso that when the compound is of formula (IB), the compound is other than 3-(5-isopropyl-4H-1,2,4-triazol-3-yl)-N- (tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine or 3-(5-cyclopropyl-4H-,2,4-triazol-3-yl)-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (1A) and (1B).
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COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES SUCH AS ALZHEIMER'S DISEASE, TYPE 2 DIABETES, AND PARKINSON'S DISEASE (Fri, 20 Sep 2013)
<p id="p-0001" num="0000">The use of 3,4,3′,4′-tetrahydroxychalcone in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease.</p>
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Compound and medical use thereof (Fri, 20 Sep 2013)
<p id="p-0001" num="0000">Provided is a levodopa prodrug that overcomes the problems attributed to the blood kinetics of levodopa such as large number of doses and the incidence of side effects due to frequent dosing. (2S)-2-Amino-3-(3,4-bis((2-(benzoyloxy)-2-methylpropanoyl)oxy)phenyl)propanoic acid, a salt thereof, or a solvate thereof is a levodopa prodrug, and provides a flat blood concentration-time profile of levodopa through oral administration, and therefore is useful as a preventive and/or therapeutic agent for Parkinson's disease and/or Parkinson's syndrome that overcomes the problems associated with pharmaceutical preparations of levodopa.</p>
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BIARYL INHIBITORS OF THE SODIUM CHANNEL (Sat, 07 Sep 2013)
The invention relates to compounds useful in treating conditions associated with voltage- gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns biaryl derivatives (e.g., compounds according to any of Formulas (I)-(XII) or Compounds (l)-(372) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.
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INHIBITORS OF POLO-LIKE KINASE (Fri, 06 Sep 2013)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="61.38mm" file="US20130231335A1-20130905-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, X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6</sup>, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.</p>
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(+)-3-HYDROXYMORPHINAN-BASED POLYCYCLE DERIVATIVES (Fri, 23 Aug 2013)
<p id="p-0001" num="0000">A (+)-3-hydroxymorphinan-based polycycle derivative of formula (I) is effective as a neuroprotective agent for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and ischemic stroke.</p>
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2-ALKOXY-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF (Fri, 16 Aug 2013)
<p id="p-0001" num="0000">The invention features 2-alkoxy-11-hydroxyaporphine derivatives that selectively bind D<sub>2</sub><sup>high </sup>receptors. The compounds are useful for imaging D<sub>2</sub><sup>high </sup>receptors and for the treatment of diseases, such as Parkinson's disease, sexual dysfunction, and depressive disorders.</p>
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Compounds and Their Use as BACE Inhibitors (Fri, 16 Aug 2013)
<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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MORPHOLINOALKYL FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE (Fri, 16 Aug 2013)
Morpholinoalkyl fumarates, pharmaceutical compositions comprising the morpholinoalkyl fumarates, and methods of using morpholinoalkyl fumarates and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed.
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1,2,4-TRIAZOLONE DERIVATIVE (Thu, 08 Aug 2013)
The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.
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1, 2, 4-TRIAZOLONE DERIVATIVE (Fri, 02 Aug 2013)
<p id="p-0001" num="0000">The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="76.20mm" file="US20130197217A1-20130801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOSITION COMPRISING XANTHOCERAS SORBIFOLIA EXTRACTS, COMPOUNDS ISOLATED FROM SAME, METHODS FOR PREPARING SAME AND USES THEREOF (Fri, 26 Jul 2013)
<p id="p-0001" num="0000">This invention provides compositions, methods and process of producing extracts from <i>Xanthoceras sorbifolia</i>. The extract comprises alkaloids, coumarins, saccharides, proteins, polysaccharides, glycosides, saponins, tannins, acid, flavonoids and others. The composition can be used for treating cancer, arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder, impotence and premature ejaculation; for preventing cerebral aging; for improving memory, cerebral functions; or for curing enuresis, frequent micturition, urinary incontinence, dementia, weak intelligence and Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions, and treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder. This invention provides compounds comprising at least one sugar, a triterpene, such as Sapogenin, and at least one side chains at Carbon 21 and 22, such as Angeloyl groups. The compounds of the present have various pharmaceutical and therapeutic applications.</p>
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BICYCLIC AMIDES FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES (Fri, 26 Jul 2013)
<p id="p-0001" num="0000">This invention relates to bicyclic amide compounds, pharmaceutical compositions and methods for use in the prevention and treatment of a variety of conditions and/or disease states including cerebral insufficiency, through the enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors as defined herein. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in other disorders wherein a deficiency in neurotrophic factors is implicated, as well as other disorders as described herein.</p>
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Methods for treating amyotrophic lateral sclerosis using pro-neurogenic compounds (Fri, 26 Jul 2013)
<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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PYRROLIDINE DERIVATIVES (Fri, 19 Jul 2013)
<p id="p-0001" num="0000">The present invention relates to compounds of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.06mm" wi="69.85mm" file="US20130184249A1-20130718-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, Z, and n are as defined herein <br/> or to a pharmaceutically active salt thereof. Compounds of the invention are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD). </p>
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Methods for Treating Parkinson's Disease Using Pro-Neurogenic Compounds (Fri, 19 Jul 2013)
<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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Levodopa prodrug mesylate hydrate (Fri, 19 Jul 2013)
<p id="p-0001" num="0000">Crystalline (2R)-2-phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylate, hydrate, methods of making the hydrate, pharmaceutical compositions containing the hydrate, and methods of using the hydrate to treat diseases or disorders such as Parkinson's disease are provided.</p>
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HETEROCYCLIC DERIVATIVES AS TRACE AMINE ASSOCIATED RECEPTORS (TAARS) (Fri, 19 Jul 2013)
The present invention relates to compounds of formula (I) wherein R1 is a one or two membered heteroaryl group, selected from the group consisting of formula (a), (b), (c), (d), (e), (f), (g), (h), (i), (j); R2 is hydrogen or halogen; or R1 and R2 may form together with the carbon atoms to with they are attached the following rings formula (k), (l), (m), (n), (o). R3 is hydrogen, halogen or lower alkyl; n is 1 or 2; R4 is phenyl, optionally substituted by one or two substituents, selected from halogen or cyano, or is pyridinyl, optionally substituted by halogen, or is tetrahydropyran, or is -NH-C(O)-phenyl, optionally substituted by halogen; R5 is hydrogen or halogen; R6 – R13 are phenyl, optionally substituted by halogen: R14 is –NH-C(O)-phenyl, substituted by halogen; R15 is hydrogen, lower alkyl substituted by halogen or is halogen; R16 is hydrogen or lower alkoxy; R17 is pyridinyl, optionally substituted by lower alkoxy or lower alkyl substituted by halogen; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, to all their corresponding enantiomers and/or optical isomers and to all tautomeric forms of compounds of formula I. The compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
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METHODS OF TREATMENT USING ARYLCYCLOPROPYLAMINE COMPOUNDS (Fri, 12 Jul 2013)
<p id="p-0001" num="0000">Described herein are methods of treating Parkinson's disease using arylcyclopropylamine compounds.</p>
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1,3-DIPHENYLPROPANE DERIVATIVES, PREPARATIONS AND USES THEREOF (Fri, 05 Jul 2013)
The present invention relates to novel 1,3-diphenylpropane derivatives, pharmaceutical compositions comprising the same and therapeutic uses thereof, in particular in the fields of human and animal health. The compounds according to the present invention have intrinsic PPAR agonist properties. They are therefore of particular interest in the treatment of metabolic and/or inflammatory diseases and particularly peripheral and central diseases associated with the metabolic syndrome, such as diverse forms of steatohepatitis, type 2 diabetes, diverse neurodegenerative disorders,such as Alzheimer'sdisease, Parkinson's disease and multiple sclerosis.
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METHODS AND COMPOSITIONS FOR TREATING PARKINSON'S DISEASE (Fri, 05 Jul 2013)
The invention discloses methods and compositions for treating or preventing Parkinson's disease by administering a compound of Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.
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Arylsulfonyl pyrazoline carboxamidine derivatives as 5-HT6 antagonists (Thu, 04 Jul 2013)
This invention concerns arylsulfonyl pyrazoline carboxamidine derivatives as antagonists of 5-HT 6 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 Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1): wherein the symbols have the meanings given in the description.
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CANNABINOID RECEPTOR MODULATORS (Fri, 28 Jun 2013)
<p id="p-0001" num="0000">The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.</p>
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NOVEL NEUROMODULATORY COMPOUNDS (Fri, 28 Jun 2013)
<p id="p-0001" num="0000">Provided herein are novel neuromodulatory compounds and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT<sub>1D </sub>and/or the 5-HT<sub>1B </sub>receptor, without agonizing the 5-HT<sub>2B </sub>receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha<sub>2A </sub>and/or the alpha<sub>2B </sub>receptors using the compounds and compositions disclosed herein. In other embodiments, provided herein are methods of agonizing dopaminergic D<sub>2 </sub>receptors and/or antagonizing or inhibiting activity of receptors such as the 5-HT<sub>2 </sub>receptors using the compounds and compositions disclosed herein.</p>
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Organosulfur Compounds for the Prevention and Treatment of Neurodegenerative Diseases (Fri, 28 Jun 2013)
<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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PEPTIDES INCORPORATING 3-AMINOADAMANTANE CARBOXYLIC ACIDS ENHANCE SYNAPTIC PLASTICITY AND ACT AS NEUROGENIC AGENTS (Fri, 28 Jun 2013)
<p id="p-0001" num="0000">The disclosed invention relates to peptides incorporating 3-aminoadamantane-1-carboxylic acids. These peptides are disclosed as surprisingly possessing neurogenic and neurotrophic properties. These pharmacological activities can advantageously be utilized for restoring or maintaining neuronal function in the CNS. In particular, the compounds can be used for treatment and prophylaxis of neurodegenerative diseases, e. g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, as well as in post-acute traumatic brain injury, or cerebral ischemia.</p>
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NOVEL NEUROMODULATORY COMPOUNDS (Fri, 28 Jun 2013)
Provided herein are novel neuromodulatory compounds and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTlD and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the aIpha2B receptors using the compounds and compositions disclosed herein. In other embodiments, provided herein are methods of agonizing dopaminergic D2 receptors and/or antagonizing or inhibiting activity of receptors such as the 5-HT2 receptors using the compounds and compositions disclosed herein.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Specific Compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="69.85mm" file="US20130157999A1-20130620-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">or pharmaceutically acceptable salts thereof,</li> <li id="ul0002-0002" num="0000">wherein m, X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>5</sup>, R<sup>6 </sup>and R<sup>7 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.</li> </ul> </li> </ul> </p>
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="69.85mm" file="US20130158006A1-20130620-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, <br/> wherein A, X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease. </p>
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="69.85mm" file="US20130158032A1-20130620-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, <br/> wherein m, n. X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease. </p>
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ALKYNE-BRIDGED HETERO-AROMATICS AND USES THEREOF (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">This invention relates to novel alkyne-bridged hetero-aromatics as described in the specification which are PDE10A inhibitors and useful for the treatment of neurological, psychiatric disorder, metabolic disorders, such as Schizophrenia, Parkinson's disease, Huntington's disease, Alzheimer's disease, learning memory disorder, drug addiction (abuse), sleeping disorder, depression, obesity, non-insulin dependent diabetes, bipolar disorder, obsessive compulsive disorder, or pain; to process for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.</p>
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="69.85mm" file="US20130158057A1-20130620-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, <br/> wherein m, n. X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease. </p>
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CONJUGATES OF POLYUNSATURATED FATTY ACIDS AND AMINE-CONTAINING COMPOUNDS AND USES THEREOF (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis.</p>
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NICOTINIC RECEPTOR TARGETED COMPOUNDS AND COMPOSITIONS (Fri, 21 Jun 2013)
The invention relates to the design and synthesis of novel anabaseine-based compounds, which are useful in treating or preventing a wide variety of conditions, including nervous system diseases or disorders, such as, schizophrenia, Alzheimer's disease, Parkinson's disease, drug dependence, and substance addiction, and compositions, kits, and methods thereof. The invention also provides novel anabaseine-based compounds, compositions, kits, and methods thereof for treating or preventing non-nerve system diseases or disorders (such as, inflammation and cancer) in a subject identified in need thereof. Certain enantiomeric compounds of the invention exhibited enhanced selectivity toward α7 nAChRs relative to alpha4beta2 nAChRs. Other enantiomeric compounds of the invention exhibited enhanced selectivity for alpha4beta2 nAChRs relative to α7 nAChRs.
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METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS (Fri, 14 Jun 2013)
<p id="p-0001" num="0000">The present invention provides compostions and methods useful for treating and preventing neurodenerative disease and neurologically related disorders by inhibition of Lp-PLA2. The compositions and methods are useful for treating and preventing diseases and disorders with abnormal blood brain barrier (BBB) function, for example neurodegenerative diseases with a permeable BBB, such as but not limited to, Alzheimer's Disease, Huntington's Disease, Parkinson's Disease and Vascular Dementia.</p>
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6-DIFLUOROMETHYL-5,6-DIHYDRO-2H-[1,4]OXAZIN-3-AMINE DERIVATIVES (Fri, 14 Jun 2013)
The invention relates to novel 6-difluoromethyl-5,6-dihydro-2H-[l,4]oxazin-3- amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebral amyloid angiopathy, multi-infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid.
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5-(3-AMINOPHENYL)-5-ALKYL-5,6-DIHYDRO-2H-[1,4]OXAZIN-3-AMINE DERIVATIVES (Fri, 14 Jun 2013)
The present invention relates to novel 5-(3-aminophenyl)-5-alkyl-5,6-dihydro- 2H-[1,4]oxazin-3-amine derivatives as inhibitors of beta-secretase, also known as beta- site amyloid cleaving enzyme, BACE, BACE 1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebral amyloid angiopathy, multi-infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid. (Formula I)
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Organosulfur compounds for the prevention and treatment of neurodegenerative diseases (Fri, 07 Jun 2013)
<p id="p-0001" num="0000">S-allylmercapto-N-acetylcysteine and related compounds 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 compounds 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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2-(PHENYL OR PYRID-3-YL) AMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE (Fri, 07 Jun 2013)
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 07 Jun 2013)
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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2-PHENYLAMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE (Fri, 07 Jun 2013)
Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 07 Jun 2013)
Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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Di-substituted amides for enhancing glutamatergic synaptic responses (Fri, 31 May 2013)
<p id="p-0001" num="0000">This invention relates to compounds, pharmaceutical compositions and methods for use in the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in disorders wherein a deficiency in neurotrophic factors is implicated, as well as in disorders of respiration such as overdose of an alcohol, an opiate, an opioid, a barbiturate, an anesthetic, or a nerve toxin, or where the respiratory depression results form a medical condition such as central sleep apnea, stroke-induced central sleep apnea, obstructive sleep apnea, congenital hypoventilation syndrome, obesity hypoventilation syndrome, sudden infant death syndrome, Rett syndrome, spinal cord injury, traumatic brain injury, Cheney-Stokes respiration, Ondines curse, Prader-Willi's syndrome and drowning. In a particular aspect, the invention relates to compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.</p>
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2,5-DISUBSTITUTED-PYRIDYL NICOTINIC LIGANDS, AND METHODS OF USE THEREOF (Fri, 17 May 2013)
Disclosed are heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. The compounds are useful for treating a mammal suffering from any one of a range of therapeutic indications, including Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism, trichotillomania, and hypothermia.
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PHENYL-SUBSTITUTED NICOTINIC LIGANDS, AND METHODS OF USE THEREOF (Fri, 17 May 2013)
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.
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ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS (Fri, 03 May 2013)
Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.
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ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS (Fri, 03 May 2013)
Disclosed are compounds of Formula (I), and salts thereof, wherein R1, RA2, RA3 and RA4, are defined herein, which have properties for positive allosteric modulation of mGluR-4 receptor sites. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating Parkinson's disease and related disorders using the same.
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 26 Apr 2013)
<p id="p-0001" num="0000">Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.</p>
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2,3,5 TRISUBSTITUTED ARYL AND HETEROARYL AMINO DERIVATIVES, COMPOSITIONS, AND METHODS OF USE (Fri, 26 Apr 2013)
Compounds are disclosed that have a formula represented by the following:(I) wherein Cy, L1 R1, R2a, R2b, R3, R4, n, and L2 are as described herein. These compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example addictive disorders, Alzheimer's Disease, anxiety disorders, ascites, autism, bipolar disorder, cancer, depression, endothelial corneal dystrophy, edema, epilepsy, glaucoma, Huntington's Disease, inflammatory pain, insomnia, ischemia, migraine, migraine with aura, migraine without aura, neuropathic pain, nociceptive neuralgia, nociceptive pain, ocular diseases, pain, itch, excessive itch, Pruritis, neuropathic pruritis, Parkinson's disease, personality disorders, postherpetic neuralgia, psychosis, schizophrenia, seizure disorders, tinnitus, and withdrawal syndromes.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 19 Apr 2013)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.24mm" wi="69.85mm" file="US20130096102A1-20130418-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">wherein m, n. X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>5</sup>, R<sup>6 </sup>and R<sup>7 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.</li> </ul> </p>
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MONO-FLUORO BETA-SECRETASE INHIBITORS (Fri, 19 Apr 2013)
Beta-secretase inhibitors, of formula (I) as described in the specification, pharmaceutical compositions comprising them and therapeutic methods using them for the treatment and/or prevention of Αβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's Disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
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Pyridyl-2-methylamino compounds, compositions and uses thereof (Fri, 29 Mar 2013)
<p id="p-0001" num="0000">Compounds are provided according to formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="69.85mm" file="US08658677-20140225-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> where R, R′, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, and R<sub>6 </sub>are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, Alzheimer's Disease, Down's syndrome, Parkinson's Disease, and others. </p>
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AMIDE COMPOUNDS, COMPOSITIONS AND APPLICATIONS THEREOF (Fri, 29 Mar 2013)
The present disclosure relates to substituted amide compounds that are inhibitors of Fatty Acid Amide Hydrolase (FAAH), their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them. These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of Fatty Acid Amide Hydrolase (FAAH), such as pain including acute and post operative pain, chronic pain, cancer pain, cancer chemotherapy induced pain, neuropathic pain, nociceptive pain, inflammatory pain, back pain, pain due to disease of various origin such as: diabetic neuropathy, neurotropic viral disease including human immunodeficient virus (HIV), herpes zoster such as post herpetic neuralgia; polyneuropathy, neurotoxicity, mechanical nerve injury, carpal tunnel syndrome, immunologic mechanisms like multiple sclerosis; sleep disorders, anxiety and depression disorders, inflammatory disorders, weight and eating disorders, Parkinson's disease, addiction, spasticity, hypertension or other disorders. The disclosure also relates to the process of preparation of the amide compounds. Formula (1). The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
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18F-LABELLED BARBITURATE COMPOUNDS FOR USE AS POSITRON EMISSION IMAGING AGENTS (Fri, 22 Mar 2013)
The present invention relates generally to the field of diagnostic methods. More specifically, the present invention pertains to certain 18F-labelled barbiturate compounds of the following formula (collectively referred to herein as "18F-fluorinated barbiturate compounds" and "18FBAR compounds") that bind to metals, for example, metals associated with protein aggregates, and as such are useful as imaging agents for positron emission imaging (e.g., positron emission tomography (PET) imaging) used in the diagnosis and monitoring of conditions involving these aggregates, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). These compounds also bind strongly to GABAA receptors and hence are also useful as imaging agents for positron emission tomography (PET) imaging used in the diagnosis, monitoring and study of diseases involving dis-regulation of these receptors, including epilepsy, schizophrenia, and mood disorders (e.g., anxiety).
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AZA-INDOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 08 Mar 2013)
<p id="p-0001" num="0000">The present invention is directed to certain Aza-Indole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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POLYMORPHS OF PRELADENANT (Fri, 22 Feb 2013)
The present invention provides novel crystalline forms of preladenant, pharmaceutical compositions comprising same, methods for their preparation and use thereof in treating a neurodegenerative disease, especially Parkinson's Disease (PD).
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NEUROPROTECTIVE POLYPHENOL ANALOGS (Fri, 22 Feb 2013)
The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzherimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.
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Pro-Neurogenic Compounds (Fri, 15 Feb 2013)
<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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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 15 Feb 2013)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF PAIN AND OTHER INDICATIONS (Fri, 01 Feb 2013)
<p id="p-0001" num="0000">The present invention is directed to a composition useful for the treatment of a FAAH mediated disease, disorder or conditions comprising a FAAH inhibitor and a second activation, comprising a selected imidazole or oxazole FAAH inhibitor and a second active agent. The compositions will be useful in the treatment of a wide range of disease, disorder, or conditions including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease. In another aspect the invention discloses herein is directed to compositions useful in the treatment of neuropathic and nociceptive pain, said compositions comprising etoricoxib.</p>
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C-MET RECEPTOR REGULATION BY ANGIOTENSIN IV (AT4) RECEPTOR LIGANDS (Fri, 25 Jan 2013)
<p id="p-0001" num="0000">The cell surface c-Met receptor, through which hepatocyte growth factor (HGF) signals are mediated, has now been identified as the Angiotensin-IV receptor (AT(4)R) in processes that include HGF-regulated cell motility, angiogenesis, cancer metastasis, adipogenesis and others. Disclosed are angiotensin-like factor compositions and methods for using them to diagnose, prevent and/or treat conditions associated with c-Met dysregulation, including cancer, obesity and conditions associated with obesity, and other disorders, for example, by altering hepatocyte growth factor activity or c-Met receptor activity by administering an angiotensin-like factor that specifically binds to a cell surface c-Met receptor. In addition, members of this group of molecules may useful for treating or preventing the development of neurodegenerative diseases like general dementia, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis and initiating recovery from traumatic brain injury and spinal cord trauma. These peptides and peptidomimetics may be therapeutically useful whenever increased neurotrophic activity would be clinically advantageous.</p>
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 18 Jan 2013)
<p id="p-0001" num="0000">The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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Chemical compounds (Fri, 18 Jan 2013)
<p id="p-0001" num="0000">The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.40mm" wi="69.85mm" file="US08598156-20131203-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, and R<sup>3 </sup>are defined herein. </p> <p id="p-0003" num="0000">The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.</p>
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION WITH REDUCED IMMUNOGENICITY (Fri, 18 Jan 2013)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 11 Jan 2013)
<p id="p-0001" num="0000">The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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NEW DERIVATIVES OF PROPARGYLAMINE HAVING NEUROPROTECTIVE CAPACITY FOR THE TREATMENT OF ALZHEIMER'S AND PARKINSON'S DISEASES (Fri, 11 Jan 2013)
<p id="p-0001" num="0000">The present invention relates to a compound of formula (I) wherein: R<sup>1 </sup>and R<sup>2 </sup>are selected from among H and C1-C10 alkyl; R<sup>3 </sup>is selected from among H, —OR<sup>4</sup>, N, —CN, —C(O)R<sup>4</sup>, —C(O)OR<sup>4</sup>, —C(O)N<sup>4</sup>R<sup>5</sup>, —C═NR<sup>4</sup>, —OC(O)R<sup>4</sup>, —NR<sup>4</sup>R<sup>5</sup>, —NR<sup>4</sup>C(O)R<sup>5</sup>, —NO<sub>2</sub>, —N═CR<sup>4</sup>R<sup>5</sup>, halogen and C1-C10 alkyl, wherein R<sup>4 </sup>and R<sup>5 </sup>are selected from among H, alkyl, alkenyl, cycloalkyl and aryl; X, Y, Z<sup>1</sup>, Z<sup>2 </sup>and Z<sup>3 </sup>are selected independently from among CH and N; A is selected from among (CH<sub>2</sub>)<sub>n</sub>, NH, O and CO, wherein n is an integer between 1 and 6, to the procedure for the obtainment of said compounds, to a pharmaceutical composition comprising said compound, and to the use thereof in the treatment of a neurodegenerative disease, more particularly treatment of Alzheimer's or Parkinson's disease.</p>
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Dopamine Transporter Inhibitors for Use in Treatment of Movement Disorders and Other CNS Indications (Fri, 28 Dec 2012)
<p id="p-0001" num="0000">The invention provides a class of dopamine transporter inhibitors of formula (I) (DAS inhibitors), packaged pharmaceuticals comprising such inhibitors, and their uses treating, or the manufacturing medicaments for treating disease conditions, including Parkinson's disease, Hoehn and Yahr Staging of Parkinson's Disease. Unified Parkinson Disease Rating Scale (UPDRS), and Schwab and England Activities of Daily Living Scale. Related business methods such as marketing the inhibitors to healthcare providers are also provided.</p>
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Cysteinyl compounds, compositions and methods of use (Fri, 28 Dec 2012)
<p id="p-0001" num="0000">Among other things, the present invention provides novel compounds capable of effectively inhibiting inflammatory responses that are mediated by G-proteins or GPCRs in neutrophils, macrophages and platelets. In particular, the compounds of the present invention act as inhibitors of edema, inhibitors of erythema and inhibitors of MPO (myeloperoxidase), pharmaceutical compositions containing the same compounds and the use thereof for the treatment of diseases that may benefit from edema, erythema and MPO inhibition, such as inflammation (acute or chronic), asthma, autoimmune diseases, and chronic obstructive pulmonary disease (COPD) (e.g., emphysema, chronic bronchitis and small airways disease, etc.), inflammatory responses of the immune system, skin diseases (e.g., reducing acute skin irritation for patients suffering from rosacea, atopic dermatitis, seborrheic dermatitis, psoriasis), irritable bowel syndrome (e.g., Chron's disease and ulcerative colitis, etc.), and central nervous system disorders (e.g., Parkinson's disease).</p>
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COMPOUNDS FOR TREATING PERIPHERAL NEUROPATHIES AND OTHER NEURODEGENERATIVE DISORDERS (Fri, 28 Dec 2012)
Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.
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Tetrahydroisoquinoline sulfonamide derivatives, the preparation thereof, and the use of the same in therapeutics (Fri, 21 Dec 2012)
<p id="p-0001" num="0000">The disclosure relates to tetrahydroisoquinoline sulfonamide compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.15mm" wi="63.33mm" file="US08524700-20130903-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R1, R2, n and B are as defined in the disclosure, their preparation and their use in therapies for the treatment of central nervous system diseases such as vigilance and sleep disorders, narcolepsy, Alzheimer's disease and other dementias, Parkinson's disease, attention disorders in hyperkinetic children, memory and learning disorders, epilepsy, schizophrenia, moderate cognitive disorders, depression, anxiety, sexual dysfunction, dizziness and travel sickness. </p>
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SUBSTITUTED BENZAMIDE DERIVATIVES (Fri, 14 Dec 2012)
<p id="p-0001" num="0000">The present invention relates to compounds of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.43mm" wi="65.36mm" file="US20120316165A1-20121213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, X, Z, Ar, and n are as described in the claims, <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">Ar is phenyl or heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, 1H-pyrazole-3-yl, 1H-pyrazole-4-yl and 1H-pyrazole-5-yl; <br/> or to a pharmaceutically suitable acid addition salt thereof, 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. </li> </ul> </p>
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SUBSTITUTED BENZAMIDE DERIVATIVES (Fri, 14 Dec 2012)
The present invention relates to compounds of formula (I) wherein R1 is hydrogen, halogen, cyano, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or C(O)NH2, or is phenyl optionally substituted by halogen, cyano or lower alkoxy substituted by halogen, or is 2,2-difluorobenzo[d][1,3]dioxol-5-yl, or is 6-(trifluoromethyl)pyrazin-2-yl or 5-(trifluoromethyl)pyrazin-2-yl or is 6-(trifluoromethyl)pyrimidin-4-yl, or is 6- (trifluoromethyl)pyridin-3-yl, or is 5-cyanopyrazin-2-yl or is 2- (trifluoromethyl)pyrimidin-4-yl; n is 1 or 2 R2 is halogen, lower alkyl or cyano and R3 is hydrogen, or R2 is hydrogen and R3 is halogen, lower alkyl or cyano; X is a bond, -NR'-, -CH2NH- or -CHR'-; R' is hydrogen or lower alkyl; Z is a bond, -CH2- or -O-; Ar is phenyl or is heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, lH-pyrazole-3-yl, 1H- pyrazole-4-yl or lH-pyrazole-5-yl; or to a pharmaceutically suitable acid addition salt thereof, 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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DETECTION OF OXIDIZED POLYPEPTIDES (Fri, 07 Dec 2012)
<p id="p-0001" num="0000">A diagnostic method for determining the absence or presence of a disease is provided. The method generally includes assaying the amount and/or types of oxidized peptides in a sample from a subject, and comparing these to the amount and types of reference oxidized polypeptides. The method may include the use of stable isotope label, affinity selection, to identify and quantify changes in oxidized peptides or oxidized proteins associated with diseases such as type II diabetes mellitus, breast cancer, and Parkinson's disease, to monitor a patient's response to a therapeutic agent (e.g., an antioxidant), and/or to monitor disease recurrence.</p>
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SULPHATED DISACCHARIDES FOR THE TREATMENT OF NEURODEGENERATIVE AND/OR NEUROVASCULAR DISEASES (Fri, 07 Dec 2012)
<p id="p-0001" num="0000">The present invention relates to the use of a series of sulphated disaccharides for the preparation of a medicament for the treatment or prevention of a neurodegenerative and/or neurovascular disease, of a traumatic brain injury or of a traumatic spinal cord injury. The present invention also relates to the use of said sulphated disaccharides for the preparation of a neuroprotective medicament or of an antioxidant medicament. The neurodegenerative and/or neurovascular diseases are preferably: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke.</p>
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INHIBITORS OF LRRK2 KINASE ACTIVITY (Fri, 30 Nov 2012)
The present invention provides compounds having a structure according to Formula I: (I) or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as Alzheimer's disease, type 2 diabetes and Parkinson's disease (Thu, 29 Nov 2012)
Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially A² amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinophathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.
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Levodopa Prodrugs, and Compositions and Uses Thereof (Fri, 23 Nov 2012)
<p id="p-0001" num="0000">(2R)-2-Phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylate and crystalline form thereof, methods of making the same, pharmaceutical compositions thereof, and methods of using the same to treat diseases or disorders such as Parkinson's disease are provided.</p>
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METAL DELIVERY AGENTS AND THERAPEUTIC USES OF THE SAME (Fri, 26 Oct 2012)
<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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Aryl compounds as PPAR ligands and their use (Fri, 26 Oct 2012)
<p id="p-0001" num="0000">The present invention relates to a compound as a peroxisome proliferator activated receptor (PPAR) activator and a hydrate, a solvate, a stereoisomer and a pharmaceutically acceptable salt thereof, and a pharmaceutical composition, a cosmetic composition, a muscle strengthening agent, a memory improving agent, a therapeutic agent for dementia and Parkinson's disease, a functional food and a feed composition containing the same.</p>
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COMPOSITIONS AND METHODS FOR INHIBITING AND/OR MODULATING EFFECTOR T-CELLS INVOLVED IN INFLAMMATORY NEURODEGENERATIVE DISEASE (Fri, 19 Oct 2012)
<p id="p-0001" num="0000">Provided are methods for treating inflammatory neurodegenerative diseases (e.g., multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, stroke/cerebral ischemia, head trauma, spinal cord injury, Huntington's disease, migraine, cerebral amyloid angiopathy, inflammatory neurodegenerative condition associated with AIDS, age-related cognitive decline; mild cognitive impairment and prion diseases in a mammal), or at least one symptom thereof in a subject by administering a therapeutic composition comprising at least one electrokinetically-altered fluids (e.g., electrokinetically-generated oxygen-enriched fluids) of the present invention. Particular aspects provide methods for inhibiting and/or modulating the function and/or activity of effector T-cells, and/or for cell-based tolerogenic therapy (e.g., by modulating development and/or function and/or activity of T<sub>REG </sub>cells and/or dendritic cells (DCs) and/or T<sub>H</sub>17 cells (e.g., RORγt<sup>+</sup> T<sub>H</sub>17 cells). In certain aspects such methods comprise ex vivo exposure of T-cells and/or APC (e.g., dendridic cells) to at least one electrokinetically-altered fluid as disclosed herein. Combination therapies are additionally provided.</p>
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NOVEL 3-SUBSTITUTED 7-IMINO-2-THIOXO-3, 7-DIHYDRO-2H-THIAZOLO [4,5-DI PYRIMIDIN-6-YL - AND PROCESS FOR PREPARATION THEREOF (Fri, 19 Oct 2012)
<p id="p-0001" num="0000">The present invention relates to novel 3-substituted (7-imino-2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl of formula 1 wherein R is selected from a group consisting of hydrogen, alkyl having carbon no up to 10, allyl, cycloalkyl, aromatic, substituted aromatics (halogen, OH, COOH, OCH<sub>3</sub>, alkyl, etc), pyridyl, piperidine, piprazine, morphine. R<sub>1 </sub>is selected from a group consisting of NH<sub>2</sub>, NHR, N(R)<sub>2</sub>(wherein R could be aliphatic or olefinic group up to 10 carbon), hetrocycles such as furan, thiophene, pyrole, prydyl, piprazine, morphine and R<sub>2 </sub>is 0 and S separately. Particularly the present invention relates to (7-Imino-3-substituted -2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-urea(15-21) and Furan-2-carboxylic acid (7-imino-3 -substituted -2-thioxo-3,7-dihydro-2H-thiazolo[4,5-d]pyrimidin-6-yl)-amide. The compounds of present invention are useful in the treatment of central nervous disorders including, Parkinson disease, Huntington's disease, attention disorder, cognition, Alzheimer disease, depression and hypertension.</p>
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SELECTIVE CYSTEINE PROTEASE INHIBITORS AND USES THEREOF (Fri, 19 Oct 2012)
The present invention relates to compounds of Formula I, II, IA-VA, IVA1-1VA5, 11IA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1 -IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease).
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Compounds for Use in the Detection of Neurodegenerative Diseases (Fri, 05 Oct 2012)
<p id="p-0001" num="0000">Provided are the use of the disclosed compounds as imaging agents and methods for in vivo imaging and detection of pathological characteristics unique to synuclein diseases, such as Parkinson's disease.</p>
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Compounds, compositions, and methods for the treatment of β-amyloid diseases and synucleinopathies (Fri, 05 Oct 2012)
<p id="p-0001" num="0000">Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of β-amyloid diseases, such as observed in Alzheimer's disease, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.</p>
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SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 05 Oct 2012)
Substituted 5-(pyrazin-2-yl)-1H-pyrazolo [3, 4-b] pyridine, 5-(pyrazin-2-yl)-1H- pyrrolo[2,3-b]pyridine and pyrazolo [3, 4-b] pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.
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METABOLITES OF 7-(2-(4-(6-FLUORO-3-METHYLBENZO[d]ISOXAZOL-5-YL)PIPERAZIN-1-YL)ETHYL)-2-(PROP-1-YNYL)-7H-PYRAZOLO[4,3-e][1,2,4]TRIAZOLO[1,5-c]PYRIMIDIN-5-AMINE AND THEIR UTILITY AS ADENOSINE A2a RECEPTOR ANTAGONISTS (Fri, 05 Oct 2012)
The present invention provides a compound of the Formula I: Formula I or a pharmaceutically acceptable salt thereof in isolated and purified form wherein R, R1 and R2 are as described herein. The compounds are adenosine A2a receptor antagonists useful in treatment of central nervous system disorders, such as Parkinsons disease, Extra-Pyramidal Syndrome (EPS) caused by treatment with an antipsychotic agent, restless legs syndrome, Huntington s disease, attention disorders, depression, stroke and psychoses.
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METABOLITES OF 2-(FURAN-2-YL)-7-(2-(4-(4-(2-METHOXYETHOXY)PHENYL)PIPERAZIN-1-YL)ETHYL)-7H-PYRAZOLO[4,3-e][1,2,4]TRIAZOLO[1,5-c]PYRIMIDIN-5-AMINE AND THEIR UTILITY AS ADENOSINE A2a RECEPTOR ANTAGONISTS (Fri, 05 Oct 2012)
The present invention provides a compound of the (formula:(I) or a pharmaceutically acceptable salt thereof in isolated and purified form. The compound is an adenosine A2a receptor antagonists useful in treatment of central nervous system disorders, such as Parkinsons disease, Extra-Pyramidal Syndrome (EPS) caused by treatment with an antipsychotic agent, restless legs syndrome, Huntington s disease, attention disorders, depression, stroke and psychoses.
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1-SUBSTITUTED 2-AZABICYCLO [3.1.1] HEPTYL DERIVATIVES USEFUL AS NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS FOR TREATING NEUROLOGIC DISORDERS (Fri, 28 Sep 2012)
<p id="p-0001" num="0000">This invention provides 2-azabicyclo[3.1.1]heptyl derivatives, and methods for producing them, which are useful therapeutic agents for preventing or treating central nervous system disorders and disease mediated by a Nicotinic Acetylcholine Receptor such as, but not limited to, Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, dementia, pain and nicotine addiction.</p>
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JNK3 MODULATORS AND METHODS OF USE (Fri, 21 Sep 2012)
<p id="p-0001" num="0000">The c-Jun NH<sub>2</sub>-terminal kinase (JNK) group of MAP kinases are activated by exposure of cells to environmental stress. The role of JNK in the brain was examined by targeted disruption of the gene that encodes the neuronal isoform JNK3. It was found that JNK3 is required for the normal response to seizure activity. Methods of screening for molecules and compounds that decrease JNK3 expression or activity are described. Such molecules or compounds are useful for treating disorders involving excitotoxicity such as seizure disorders, Alzheimer's disease, Huntington disease, Parkinson's disease, and ischaemia.</p>
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Use of Indole Derivatives as Nurr-1 Activators for the Application Thereof as a Medicament for the Treatment of Parkinson's Disease (Fri, 14 Sep 2012)
<p id="p-0001" num="0000">Compounds derived from indole, notably useful in therapeutics, selected from: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">i) the compounds of formula:</li> </ul> </li> </ul> </p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.58mm" wi="69.85mm" file="US20120232070A1-20120913-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and <ul id="ul0003" list-style="none"> <li id="ul0003-0001" num="0000"> <ul id="ul0004" list-style="none"> <li id="ul0004-0001" num="0000">ii) the pharmaceutically acceptable salts of the compounds of formula (I); <br/> in which R1, R2, R3, R4, R5, R6, R8, R9 and Cy have defined meanings, and the use of such compounds in pharmaceuticals for the treatment of neurodegenerative diseases, particularly Parkinson's disease. </li> </ul> </li> </ul> </p>
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3,4-DIHYDRO-PYRROLO[1,2-a]PYRAZIN-1-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 14 Sep 2012)
The present invention relates to novel 3,4-dihydro-pyrrolo[l,2-a]pyrazin-1-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.
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COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Sat, 08 Sep 2012)
Compounds and their pharmaceutically acceptable salts for treatment of synucleinopathies, such as Parkinson's disease and tauopathies.
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6,7-DIHYDRO-PYRAZOLO[1,5-A]PYRAZIN-4-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Sat, 08 Sep 2012)
The present invention relates to novel 6,7-dihydro-pyrazolo[1,5-a]pyrazin-4-yl-amine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACEl, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.
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COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Sat, 08 Sep 2012)
Disclosed are compounds of Formula I: and the pharmaceutically acceptable salts thereof, wherein "A" is S-; -SO-, -SO2-, -O- or NRa-, and Ra, and R1 through R5 are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.
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Hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 07 Sep 2012)
<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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Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as Alzheimer's disease, type 2 diabetes and Parkinson's disease (Fri, 07 Sep 2012)
<p id="p-0001" num="0000">Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.</p>
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CRYSTALLINE FORMS AND PROCESSES FOR THE PREPARATION OF CONDENSED AZACYCLES ( CANNABINOID RECEPTOR MODULATORS) (Fri, 31 Aug 2012)
The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)- 1a,2,5.5a-tetrahydro- 1 H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)- 1 - hydroxymcthyl-2.2-dimcthyl-propyl)-amidc (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor and are therefore useful in t treatment of CB2 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 rumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis; and Parkinson's disease.
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Piperazinyl-propyl-pyrazole derivatives as dopamine D4 receptor antagonists, and pharmaceutical compositions containing the same (Fri, 17 Aug 2012)
<p id="p-0001" num="0000">The present invention relates to a novel piperazinyl-propyl-pyrazole derivative, a method of its preparation and a pharmaceutically acceptable composition comprising the same. The novel piperazinyl-propyl-pyrazole derivative of the present invention has superior selective affinity for dopamine D<sub>4 </sub>receptor, can effectively inhibit psychotic behavior (cage climbing) induced by apomorphine, and has relatively low adverse effects in mouse rotarod test. Therefore, it can be developed as a therapeutic agent for the treatment and prevention of central nervous system (CNS) disorders, in particular, schizophrenia, attention deficit hyperactivity disorder, depression, stress diseases, panic disorder, phobia, obsessive-compulsive disorder, posttraumatic stress disorder, cognitive disorder, Alzheimer's disease, Parkinson's disease, anxiety, paraphrenia, mania, seizure disorder, personality disorder, migraine, drug addiction, alcohol addiction, obesity, eating disorder, and sleeping disorder.</p>
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Pharmaceutical composition for treating or preventing degenerative and inflammatory diseases (Fri, 17 Aug 2012)
<p id="p-0001" num="0000">The present invention relates to a pharmaceutical composition useful for treating or preventing inflammatory disease and cell damage, and a method for treating or preventing inflammatory disease and cell damage. The present invention uses the 2-hydroxybenzoic acid derivative represented by the specific chemical formula or its pharmaceutically acceptable salt. The compound of the present invention is useful for treating or preventing cell damage and inflammatory disease including gastritis, gastric ulcer, pancreatitis, colitis, arthritis, diabetes, arteriosclerosis, nephritis, hepatitis, Alzheimer's disease, Parkinson's disease and Lou Gehrig's disease.</p>
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SELECTIVE CALCIUM CHANNEL ANTAGONISTS (Fri, 27 Jul 2012)
The present invention relates to compositions and methods for the treatment and/or prevention of neurodegenerative disorders, e.g., Parkinson's disease (PD). In particular, the present invention provides compositions comprising selective antagonists of calcium ion channels (e.g., cav 1.3 -type ion channels), and methods of use thereof to treat or prevent neurodegenerative disorders.
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NOVEL COMPOUNDS (Fri, 20 Jul 2012)
<p id="p-0001" num="0000">The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by LRRK2 kinase activity, particularly Parkinson's disease and Alzheimer's disease.</p>
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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses (Fri, 06 Jul 2012)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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Magnesium compositions and uses thereof for neurological disorders (Fri, 06 Jul 2012)
<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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4,5-DIHYDRO-OXAZOL-2YL DERIVATIVES (Fri, 29 Jun 2012)
<p id="p-0001" num="0000">The invention relates to compounds of formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.91mm" wi="59.44mm" file="US20120165294A1-20120628-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein <br/> R<sup>1</sup>, R<sup>2</sup>, X, Y, and n are defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The invention also provides pharmaceutical compositions and methods of manufacture of such compounds. The compounds are useful for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases are depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and 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. </p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 29 Jun 2012)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one of Fms protein kinase or Kit protein kinase. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of Fms protein kinases and/or Kit protein kinases, 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, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, myelopreparation for autologous transplantation, transplant rejection, nephritis, nephropathy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastomas, neurofibromatosis, osteolytic bone metastases, and giant cell tumors.</p>
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Compounds and their use as BACE inhibitors (Fri, 29 Jun 2012)
<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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Compounds and their use as BACE inhibitors (Fri, 29 Jun 2012)
<p id="p-0001" num="0000">The present invention relates to novel 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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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 29 Jun 2012)
The present invention relates to novel compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Αβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
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COMPOUNDS AND THEIR USE AS BACE INHIBITORS (Fri, 29 Jun 2012)
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 Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
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5,6-DIHYDRO-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 29 Jun 2012)
The present invention relates to novel 5,6-dihydro-imidazo[1,2-a]pyrazin-8- ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, cerebrovascular amyloid angiopathy, multi- infarct dementia, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid.
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PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 22 Jun 2012)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.10mm" wi="69.85mm" file="US20120157427A1-20120621-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">or pharmaceutically acceptable salts thereof,</li> <li id="ul0001-0002" num="0000">wherein X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.</li> </ul> </p>
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Magnesium compositions and uses thereof for metabolic disorders (Fri, 22 Jun 2012)
<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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8-TRIAZOLYLXANTHINE DERIVATIVES, PROCESSES FOR THEIR PRODUCTION AND THEIR USE AS ADENOSINE RECEPTOR ANTAGONISTS (Fri, 15 Jun 2012)
The invention relates to derivatives of the general formulae (I) and (II) to processes for the production thereof, to pharmaceutical preparations containing said compounds and/or physiologically compatible salts or solvates or prodrugs which can be produced therefrom as well as to the pharmaceutical use of said compounds, the salts or solvates thereof as adenosine receptor antagonists, in particular for the treatment of neurodegenerative disorders, e.g. stroke, amylotrophic lateral sclerosis, dementia, Alzheimer's disease, Parkinson's disease, ischemia/reperfusion injury, inflammation, and/or neurological disorder. The blockade of adenosine receptors could also be useful for other indications regarding the metabolism, e.g. diabetic retinopathy, diabetes mellitus, hyperbaric oxygen - induced retinopathy and/or obesity. Applications could also be the treatment of allergic diseases and autoimmune diseases, including mast cell degranulation, asthma, bronchoconstriction, pulmonary fibrosis, inflammatory or obstructive airways disease and/or chronic obstructive pulmonary disease (COPD). In addition, they could be used to treat cancer. The diseases associated with adenosine receptors are also diabetes, diarrhea, inflammatory bowel disease and/or gastrointestinal tract disorders. Adenosine receptor antagonists could be effective for treating a hepatic disease or condition for reducing fat deposition in the liver or fibrosis of the liver. The use of compounds of general formulae I or II can be associated with many applications e.g., scleroderm arthritis, atherosclerosis, urticaria, myocardial infarction, myocardial reperfusion after ischemia, vasodilation, hypertension, hypersensitivity, myocardial ischemia, heart attack and/or retinopathy of prematurity.
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3-SUBSTITUTED-6-(PYRIDINYLMETHOXY)-PYRROLOPYRIDINE COMPOUNDS (Fri, 08 Jun 2012)
The invention provides certain 3-substituted-6-(pyridinylmethoxy)-pyrrolopyridine compounds, particularly compounds of formula I and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat Parkinsons disease Formula (I).
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NOVEL FLUORINATED SULFAMIDES EXHIBITING NEUROPROTECTIVE ACTION AND THEIR METHOD OF USE (Fri, 08 Jun 2012)
Pharmaceutical compositions of the invention include fluorinated sulfamide derivatives having a disease-modifying action in the treatment of diseases associated with excitotoxicity and accompanying oxidative stress that include epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, heavy metal toxicity and any neurodegenerative disease involving glutamate toxicity.
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Substituted Esters as Cannabinoid-1 Receptor Modulators (Fri, 01 Jun 2012)
<p id="p-0001" num="0000">Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.</p>
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FLAVAGLINE DERIVATIVES AS NEUROPROTECTIVE AGENTS (Fri, 25 May 2012)
The present invention discloses new flavagline derivatives (I) and the use of these compounds as neuroprotective and/or cardioprotective and/or antitumoral agents. In particular, the present invention discloses the use of these flavagline derivatives to prevent or limit the neurotoxicity of an antineoplastic agent. The use of these new compounds to prevent or treat a neurodegenerative disease of the nervous system, in particular Parkinson's disease, is also disclosed.
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NEW SALTS SUITABLE FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS (Fri, 25 May 2012)
The invention relates to non-sulfonic acid type new rasagiline salts, a process for the preparation thereof, pharmaceutical compositions containing said salts and the use thereof for the treatment or prophylaxis of various diseases, namely Parkinson's disease, amnesia, mental disorders, depression, hyperactive syndrome, affective disease, neurodegenerative disease, neurotoxic injury, cerebral ischemy, traumatic head injury, traumatic vertebral injury, schizophrenia, attention defective disorder, multiple sclerosis, withdrawal symptoms or the damage of the optic nerve.
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PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Sat, 19 May 2012)
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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BISMUTH-CONTAINING COMPOUNDS FOR MODULATING PROPERTIES OF BIOLOGICALLY ACTIVE AGENTS (Sat, 19 May 2012)
Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth- containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.
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4-(p-quinonyl)-2-hydroxybutanamide derivatives for treatment of mitochondrial diseases (Fri, 18 May 2012)
<p id="p-0001" num="0000">Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.</p>
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Bicyclic amide derivatives for enhancing glutamatergic synaptic responses (Fri, 18 May 2012)
<p id="p-0001" num="0000">This invention relates to compounds, pharmaceutical compositions and methods for use in the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors. These brain networks, which are involved in cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in disorders wherein a deficiency in neurotrophic factors is implicated, as well as conditions such as stroke-induced central sleep apnea, obstructive sleep apnea, congenital hypoventilation syndrome, among others. In a particular aspect, the invention relates to bicyclic amide compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.</p>
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BISMUTH-CONTAINING COMPOUNDS, COORDINATION POLYMERS, METHODS FOR MODULATING PHARMACOKINETIC PROPERTIES OF BIOLOGICALLY ACTIVE AGENTS, AND METHODS FOR TREATING PATIENTS (Fri, 11 May 2012)
<p id="p-0001" num="0000">Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.</p>
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Inhibitors of Polo-Like Kinase (Fri, 11 May 2012)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="55.37mm" file="US20120115848A1-20120510-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, U<sup>1</sup>, U<sup>2</sup>, U<sup>3</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.</p>
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Imidazole derivatives useful as modulators of FAAH and as FAAH imaging agents (Fri, 11 May 2012)
<p id="p-0001" num="0000">The present invention is directed to certain Inidazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.</p>
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DIHYDROOXAZOL-2-AMINE DERIVATIVES (Fri, 11 May 2012)
The invention relates to compounds of formula (I) wherein R1 is hydrogen or lower alkyl; R2 is hydrogen or is heteroaryl, optionally substituted by one or more halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, S-lower alkyl, S(O)-lower alkyl, S(O)2-lower alkyl, C(O)-lower alkyl or C3-6-cycloalkyl; R3 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, S-lower alkyl, S(O)-lower alkyl, S(O)2-lower alkyl, C(O)-lower alkyl or C3-6-cycloalkyl; R4 is hydrogen or lower alkyl; (A) is phenyl or pyridinyl, wherein the N-atom may be in different positions; X is a bond or CH(CF3)-; Ar is aryl or heteroaryl, optionally substituted by one or more R3; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as 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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Dihydrooxazol-2-amine derivatives (Fri, 04 May 2012)
<p id="p-0001" num="0000">The invention relates to compounds of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.07mm" wi="55.20mm" file="US08673950-20140318-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, X, Ar, and</li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="23.54mm" wi="11.51mm" file="US08673950-20140318-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">are defined herein</li> <li id="ul0002-0002" num="0000">or to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as 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.</li> </ul> </p>
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LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY (Fri, 04 May 2012)
Disclosed are compounds of Formula (I): and the pharmaceutically acceptable salts thereof, wherein "A" is S-; -SO-, -SO2-, -O- or NRac-, wherein Rac is H, or C1-20 alkyl and R1 through R5 are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.
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Pharmaceutical composition comprising rotigotine salts (acid or Na), especially for iontophoresis (Fri, 27 Apr 2012)
<p id="p-0001" num="0000">The present invention relates to new salts of 6-(propyl-(2-thiophen-2-ylethyl)amino)tetralin-1-ol (rotigotine), their use as a medicament, for example for the treatment of CNS disorders like Parkinson Disease, RLS, fybromyalgia and/or depression, in particular through electromotive administration. The present invention relates to pharmaceutical formulations suitable for iontophoresis that provide enhanced iontophoretic delivery of rotigotine to at least one target tissue. The formulations are further characterized by good to excellent solubility of the salts in aqueous solutions.</p>
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GASTRIC RETENTIVE DOSAGE FORMS FOR EXTENDED RELEASE OF ACAMPROSATE INTO THE UPPER GASTROINTESTINAL TRACT (Fri, 20 Apr 2012)
Gastric retentive dosage forms for sustained reiease of acamprosate are described which may allow once- or twice-daily dosing for both acute and long-term treatment of a disorder including alcohol dependence, tinnitus, sleep apnea, Parkinson's disease, levodopa-induced dyskinesias in Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, Cortical spreading depression, migraine, schizophrenia, anxiety, tardive dyskinesia, spasticity, multiple sclerosis, various types pain, or binge eating. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.
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ENGINEERED POLYPEPTIDES HAVING ENHANCED DURATION OF ACTION (Fri, 20 Apr 2012)
Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.
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PROPARGYL-TRIFLUOROMETHOXY-AMINOBENZOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND USE (Fri, 20 Apr 2012)
Disclosed are novel derivatives of propargyl-trifluoromethoxy-amino-benzothiazole which are effective in treating neurologic disorders, including Parkinson's disease and multiple sclerosis.
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INHIBITORS OF POLO-LIKE KINASE (Fri, 13 Apr 2012)
The present invention provides compounds having a structure according to Formula (I):or a salt or solvate thereof, wherein ring A, U1, U2, U3, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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COMPOSITIONS AND METHODS FOR THE PREVENTION AND TREATMENT OF BRAIN DISEASES AND CONDITIONS (Fri, 30 Mar 2012)
<p id="p-0001" num="0000">Disclosed herein are compounds, extracts, and active fractions of the plant <i>Geum japonicum </i>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.</p>
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CHEMICAL COMPOUNDS (Fri, 30 Mar 2012)
<p id="p-0001" num="0000">The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.06mm" wi="69.85mm" file="US20120077828A1-20120329-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, and R<sup>3 </sup>are defined herein.</p> <p id="p-0004" num="0000">The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.</p>
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GASTRIC RETENTIVE DOSAGE FORMS FOR EXTENDED RELEASE OF ACAMPROSATE INTO THE UPPER GASTROINTESTINAL TRACT (Fri, 30 Mar 2012)
<p id="p-0001" num="0000">Gastric retentive dosage forms for sustained release of acamprosate are described which may allow once- or twice-daily dosing for both acute and long-term treatment of a disorder including alcohol dependence, tinnitus, sleep apnea, Parkinson's disease, levodopa-induced dyskinesias in Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, Cortical spreading depression, migraine, schizophrenia, anxiety, tardive dyskinesia, spasticity, multiple sclerosis, various types pain, or binge eating. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.</p>
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FUSED TRICYCLIC COMPOUNDS AS ADENOSINE RECEPTOR ANTAGONIST (Fri, 30 Mar 2012)
The present disclosure relates to fused tricyclic compounds of formula (I) or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts, or pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by thereof as A2A adenosine receptor antagonists. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders that may be susceptible to improvement by the mediation of adenosine A2A receptor. Such conditions include, but are not limited to, Parkinsons disease, restless leg syndrome, Alzheimers disease, neurodegenerative disorder, inflammation, wound healing, dermal fibrosis, nocturnal myoclonus, cerebral ischaemia, myocardial ischemia, Huntington's disease, multiple system atrophy, corticobasal degeneration, Wilson's disease or other disorders of basal ganglia which results in dyskinesias, post traumatic stress disorder, hepatic cirrhosis, sepsis, spinal cord injury, retinopathy, hypertension, social memory impairment, depression, neuroprotection, narcolepsy or other sleep related disorders, attention deficit hyperactivity disorder, drug addiction, post traumatic stress disorder and vascular injury and the like. The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
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Novel Glutamic Acid Decarboxylase (GAD) Chimera And Methods Of Use (Fri, 23 Mar 2012)
<p id="p-0001" num="0000">The invention relates to a novel Glutamic Acid Decarboxylase (GAD). More specifically, novel DNA and protein sequences relating to GAD. Additionally, the invention discloses a novel composition and related methods for treating neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, epilepsy, and the like, using viral and non-viral delivery systems that deliver therapeutic agents to specific regions of the brain. More specifically, using an adeno-associated viral vector to deliver a nucleotide sequence encoding a novel glutamic acid decarboxylase (GAD) to specific regions of the brain that are over stimulated or disinhibited in various diseases, including neurodegenerative diseases</p>
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CONJUGATES OF POLYUNSATURATED FATTY ACIDS AND AMINE-CONTAINING COMPOUNDS AND USES THEREOF (Fri, 16 Mar 2012)
Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis.
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Pharmacologically-active vanilloid carbamates (Fri, 09 Mar 2012)
<p id="p-0001" num="0000">This application relates to pharmacologically-active vanilloid compounds which are useful for the treatment of various anti-inflammatory states characterized by inhibition of FAAH, such as, Alzheimer's dementia, Parkinson's disease, depression, pain, rheumatoid arthritis, pathophysiology of mood disorders, multiple sclerosis, and inflammation, or antagonism of TRPV1, such as, for example, Huntington's disease, hypertension, arthritis, allergic airway inflammation, Crohn's disease, ulcerative colitis, and neuropathic pain.</p>
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2 - (BENZYLOXY) BENZAMIDES AS LRRK2 KINASE INHIBITORS (Fri, 09 Mar 2012)
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 diseases characterised by LRRK2 kinase activity, for example Parkinson's disease or Alzheimer's disease.
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β- and γ-diketones and γ-hydroxyketones as <i>WNT</i>/β-catenin signaling pathway activators (Fri, 24 Feb 2012)
<p id="p-0001" num="0000">The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones 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 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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DIKETONES AND HYDROXYKETONES AS CATENIN SIGNALING PATHWAY ACTIVATORS (Fri, 24 Feb 2012)
The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones or analogs thereof, that activate Wnt/p-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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QUINAZOLINONE COMPOUNDS (Fri, 17 Feb 2012)
<p id="p-0001" num="0000">The present invention relates to quinazolinone compounds, processes for their preparation and their use as pharmaceutical agents for the treatment of Parkinson's disease (PD). The quinazolinone compounds are of general formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.14mm" wi="57.32mm" file="US20120040980A1-20120216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SMALL MOLECULE ACTIVATORS OF MITOCHONDRIAL FUNCTION (Fri, 17 Feb 2012)
<p id="p-0001" num="0000">Methods for improving mitochondrial function, decreasing iron accumulation, and/or decreasing oxidative stress by exposing cells or treating a subject to compounds or compositions of the general formula (I) are described that are beneficial in treating, for example, diseases and conditions such as Friedreich's ataxia, normal aging, and various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Furthermore, such compounds are useful as probes for identifying defects in mitochondrial metabolism, mitochondrial iron accumulation, cellular stress among other mitochondrial diseases and helping to identify compounds active in overcoming such defects.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.15mm" wi="56.98mm" file="US20120041023A1-20120216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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USE OF PRODRUGS OF GABA ANALOGS FOR TREATING DISEASES (Fri, 17 Feb 2012)
<p id="p-0001" num="0000">Methods of using prodrugs of GABA analogs and pharmaceutical compositions thereof to treat migraine, fibromyalgia, amyotrophic lateral sclerosis, irritable bowel syndrome, social phobia, Parkinson's disease, asthma, cough, or chronic obstructive pulmonary disease, and pharmaceutical compositions of prodrugs of GABA analogs useful in treating migraine, fibromyalgia, amyotrophic lateral sclerosis, irritable bowel syndrome, social phobia, Parkinson's disease, asthma, cough, or chronic obstructive pulmonary disease are disclosed.</p>
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METHODS FOR PREVENTING AND/OR TREATING DEGENERATIVE DISORDERS OF THE CENTRAL NERVOUS SYSTEM (Thu, 16 Feb 2012)
The present invention provides methods for preventing and/or treating degenerative disorders of the central nervous system using 5- (fluoromethyl)piperdine-3,4-diol, 5-(chloromethyl)piperdine-3,4-diol, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or any combination of two or more thereof. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.
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GLYCOLIPIDS AS TREATMENT FOR DISEASE (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">This invention provides compounds, compositions, and methods for treating a disorder selected from cancer, hyperinsulinemia, hypoglycemia, hyperinsulinemia with hypoglycemia, atypical Parkinson's disease, Huntington's disease, multiple systems atrophy, GM3 synthase deficiency, GM2 synthase deficiency or tauopathy.</p>
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Cycloalkyl-hydroxyl compounds and compositions for cholesterol management (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
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Di-substituted amides for enhancing glutamatergic synaptic responses (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">This invention relates to compounds, pharmaceutical compositions and methods for use in the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in disorders wherein a deficiency in neurotrophic factors is implicated, as well as in disorders of respiration such as overdose of an alcohol, an opiate, an opioid, a barbiturate, an anesthetic, or a nerve toxin, or where the respiratory depression results form a medical condition such as central sleep apnea, stroke-induced central sleep apnea, obstructive sleep apnea, congenital hypoventilation syndrome, obesity hypoventilation syndrome, sudden infant death syndrome, Rett syndrome, spinal cord injury, traumatic brain injury, Cheney-Stokes respiration, Ondines curse, Prader-Willi's syndrome and drowning. In a particular aspect, the invention relates to compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.</p>
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Compounds, Compositions, and Methods for the Treatment of Beta-Amyloid Diseases and Synucleinopathies (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.</p>
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PLASMALOGEN COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND METHODS FOR TREATING DISEASES OF THE AGING (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">Described herein are routes of synthesis and therapeutic uses of 1-alkyl, 2-acyl glycerol derivatives of formula I: which when administered to mammalian biological systems result in increased cellular concentrations of specific sn-2 substituted ethanolamine plasmalogens independent of the ether lipid synthesis capacity of the system. Elevating levels of the specific sn-2 substituted species in this way can cause lowering of membrane cholesterol levels and the lowering of amyloid secretion. These compounds can be used for the treatment or prevention of diseases of aging associated with increased membrane cholesterol, increased amyloid, and decreased plasmalogen levels, such as neurodegeneration (including Alzheimer's disease, Parkinson's disease and age-related macular degeneration), cognitive impairment, dementia, cancer (e.g. prostate, lung, breast, ovarian, and kidney cancers), osteoporosis, bipolar disorder and vascular diseases (such as atherosclerosis, hypercholesterolemia).</p>
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Specific diarylhydantoin and diarylthiohydantoin compounds (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">Compositions, such as pharmaceutical compositions, comprising specific diarylhydantoin and diarylthiohydantoin compounds, or salts or solvates thereof, are provided. Isolated and purified forms of the compounds are also described, as are unit dosage forms, compositions of substantially pure compound and kits comprising the compounds. The compounds and pharmaceutical compositions thereof may find use in the prevention and/or treatment of a variety of conditions, including prostate cancer, Parkinson's disease, Alzheimer's disease, and others.</p>
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ARYLSULFONAMIDE DERIVATIVES, COMPOSITIONS, AND METHODS OF USE (Fri, 10 Feb 2012)
The present invention provides acylsulfonamides including bumetanide derivatives and compositions comprising such analogs. The present invention also provides pharmaceutical compositions containing these compounds and methods for their use. All of these analogs are particularly useful for the treatment and/or prophylaxis of conditions that involve the Na+K+Cl- co-transporter or GABAA receptor including but not limited to addictive disorders, Alzheimer's Disease, anxiety disorders, ascites, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (autism), bipolar disorder, cancer, the improvement of cognitive function, cognitive impairment, cognitive dysfunction, depression, endothelial corneal dystrophy, edema, epilepsy, glaucoma, Huntington's Disease, inflammatory pain, insomnia, ischemia, migraine, migraine with aura, migraine without aura, neuropathic pain, nociceptive neuralgia, nociceptive pain, ocular diseases, pain, Parkinson's disease, periodic limb movement disorder (PLMD), personality disorders, postherpetic neuralgia, psychosis, restless legs syndrome (RLS), schizophrenia, seizure disorders, spasticity, tinnitus, and withdrawal syndromes.
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ARYLSULFONAMIDE DERIVATIVES, COMPOSITIONS, AND METHODS OF USE (Fri, 10 Feb 2012)
The present invention provides acylsulfonamides including bumetanide derivatives and compositions comprising such analogs. The present invention also provides pharmaceutical compositions containing these compounds and methods for their use. All of these analogs are particularly useful for the treatment and/or prophylaxis of conditions that involve the Na+K+Cl- co-transporter or GABAA receptor including but not limited to addictive disorders, Alzheimer's Disease, anxiety disorders, ascites, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (autism), bipolar disorder, cancer, the improvement of cognitive function, cognitive impairment, cognitive dysfunction, depression, endothelial corneal dystrophy, edema, epilepsy, glaucoma, Huntington's Disease, inflammatory pain, insomnia, ischemia, migraine, migraine with aura, migraine without aura, neuropathic pain, nociceptive neuralgia, nociceptive pain, ocular diseases, pain, Parkinson's disease, periodic limb movement disorder (PLMD), personality disorders, postherpetic neuralgia, psychosis, restless legs syndrome (RLS), schizophrenia, seizure disorders, spasticity, tinnitus, and withdrawal syndromes.</p>
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PRO-NEUROGENIC COMPOUNDS (Fri, 27 Jan 2012)
<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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HEXACYCLIC POLYKETIDES AS KINASE INHIBITORS (Fri, 27 Jan 2012)
Compounds of general formula (I) wherein the R1, R2, R3 and R4 groups are each independently selected from the group consisting of hydrogen, acyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, -CONH2, alkali metal, and sugar and X1, X2 groups are each independently selected from the group consisting of hydrogen and halogen, or a pharmaceutically acceptable salt, solvate, tautomer or stereoisomer thereof, a method of producing them, and their use for the treatment of cancer, Alzheimer's disease, Parkinson's disease, frontoparietal dementia, corticobasal degeneration, Pick's disease, cerebrovascular accidents, peripheral neuropathies, brain, spinal cord trauma, atherosclerosis, balloon injury induced restenosis, pulmonary fibrosis, and liver fibrosis, graft versus host disease (GvHD), transplant rejection, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, asthma, psoriasis, human multiple myeloma, T cell acute lymphoblastic leukemia and Hodgkin's disease, as protein kinase inhibitors.
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Therapeutic agents useful for treating pain (Fri, 20 Jan 2012)
<p id="p-0001" num="0000">A compound of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="18.71mm" file="US08604037-20131210-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Ar<sub>1</sub>, A, R<sub>3</sub>, x, and m are as disclosed herein and Ar<sub>2 </sub>is a benzothiazolyl, benzooxazolyl, or benzoimidazolyl group or a pharmaceutically acceptable salt thereof (a “Benzoazolylpiperazine Compound”), compositions comprising a Benzoazolylpiperazine Compound, and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound are disclosed. </p>
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PRO-NEUROGENIC COMPOUNDS (Fri, 13 Jan 2012)
This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.
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PRO-NEUROGENIC COMPOUNDS (Fri, 13 Jan 2012)
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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Hydroxyl compounds and compositions for cholesterol management and related uses (Thu, 12 Jan 2012)
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.
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Therapeutic agents useful for treating pain (Fri, 06 Jan 2012)
<p id="p-0001" num="0000">A compound of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="18.71mm" file="US08536177-20130917-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Ar<sub>1</sub>, A, R<sub>3</sub>, x, and m are as disclosed herein and Ar<sub>2 </sub>is a benzothiazolyl, benzooxazolyl, or benzoimidazolyl group or a pharmaceutically acceptable salt thereof (a “Benzoazolylpiperazine Compound”), compositions comprising a Benzoazolylpiperazine Compound, and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound are disclosed. </p>
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Hydroxyl compounds and compositions for cholesterol management and related uses (Thu, 05 Jan 2012)
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.
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Substituted Isoindoles (Fri, 30 Dec 2011)
<p id="p-0001" num="0000">The present invention relates to novel 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 Downs 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 Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer 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> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.18mm" wi="55.29mm" file="US20110319426A1-20111229-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BENZOARYLUREIDO COMPOUNDS, AND COMPOSITION FOR PREVENTION OR TREATMENT OF NEURODEGENERATIVE BRAIN DISEASE CONTAINING THE SAME (Fri, 30 Dec 2011)
<p id="p-0001" num="0000">Novel benzoarylureido compounds and a use thereof for prevention and/or treatment of the neurodegenerative brain disease are provided. The neurodegenerative brain diseases may include Alzheimer's disease, dementia, Parkinson's disease, stroke, amyloidosis, Pick's disease, Lou Gehrig's disease, Huntington's disease, Creutzfeld-Jakob disease, and the like.</p>
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PEPTIDES INCORPORATING 3-AMINOADAMANTANE CARBOXYLIC ACIDS ENHANCE SYNAPTIC PLASTICITY AND ACT AS NEUROGENIC AGENTS (Fri, 30 Dec 2011)
The disclosed invention relates to peptides incorporating 3-aminoadamantane-1-carboxylic acids. These peptides are disclosed as surprisingly possessing neurogenic and neurotrophic properties. These pharmacological activities can advantageously be utilized for restoring or maintaining neuronal function in the CNS. In particular, the compounds can be used for treatment and prophylaxis of neurodegenerative diseases, e. g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, as well as in post-acute traumatic brain injury, or cerebral ischemia.
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Peptides incorporating 3-aminoadamantane carboxylic acids enhance synaptic plasticity and act as neurogenic agents (Thu, 29 Dec 2011)
The disclosed invention relates to peptides incorporating 3-aminoadamantane-1-carboxylic acids. These peptides are disclosed as surprisingly possessing neurogenic and neurotrophic properties. These pharmacological activities can advantageously be utilized for restoring or maintaining neuronal function in the CNS. In particular, the compounds can be used for treatment and prophylaxis of neurodegenerative diseases, e. g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, as well as in post-acute traumatic brain injury, or cerebral ischemia.
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Process for the preparation of (6S)-(-)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) (Fri, 16 Dec 2011)
<p id="p-0001" num="0000">The present invention describes a novel process for the preparation of (6S)-(−)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) comprising: (a) acetylating (S)-(−)-5-hydroxy-N-n-propyl-2-aminotetraline to afford the acetate; (b) reacting this acetate, (−)-5-acetoxy-N-n-propyl-2-aminotetraline, with 2-(2-thienyl)ethanol 2-nitrobenzenesulfonate; (d) hydrolyzing (6S)-(−)-1-acetoxy-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthalene to afford (6S)-(−)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) and (d) purifying rotigotine either by the acetylation reaction and subsequent hydrolysis of the formed acetate or by salification of rotigotine through hydrochloride or hydrobromide formation and subsequent base release. Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.</p>
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5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 16 Dec 2011)
The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta- amyloid.
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5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) (Fri, 16 Dec 2011)
The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta- amyloid.</p>
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SUBSTITUTED AZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITION CONTAINING THE DERIVATIVES, AND METHOD FOR TREATING PARKINSON'S DISEASE USING THE SAME (Fri, 09 Dec 2011)
<p id="p-0001" num="0000">Provided are a substituted azole derivative and pharmaceutically acceptable salts thereof, a pharmaceutical composition including an effective amount of the derivative, and a method for treating Parkinson's disease in a mammal including administering an effective amount of the compound to the mammal. The azole derivative of the following Formula (I) and pharmaceutically useful salts thereof have an efficacy against Parkinson's disease from inhibitory effects of the activity of MAO-B.</p>
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 09 Dec 2011)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.24mm" wi="69.85mm" file="US20110301141A1-20111208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, <br/> wherein m, n. X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>5</sup>, R<sup>6 </sup>and R<sup>7 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease. </p>
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 09 Dec 2011)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.
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ORGANIC COMPOUNDS (Fri, 09 Dec 2011)
The present invention relates to (1- or 2- and/or 5 and/or 7-substituted)-(3-oxy)-(4H, 4-imino, 4-thioxo or 4-oxo)-pyrazolo[3,4-d]pyrimidin-6-ones, e.g., a compound of formula II as described below, processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them. Of particular interest are novel compounds useful as inhibitors of phosphodiesterase 1 (PDE1), e.g., in the treatment of diseases involving disorders of the dopamine D1 receptor intracellular pathway, such as Parkinson's disease, depression, narcolepsy, damage to cognitive function, e.g., in schizophrenia, or disorders that may be ameliorated through enhanced progesterone-signaling pathway, e.g., female sexual dysfunction.
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AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS (Fri, 09 Dec 2011)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.</p>
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NEW ADENOSINE RECEPTOR LIGANDS AND USES THEREOF (Thu, 08 Dec 2011)
The present invention provides new compounds with high affinity for adenosine A<sb>2A</sb> receptors. It also provides antagonists of adenosine A<sb>2A</sb> receptors and their use as medicaments for the treatment and/or prophylaxis of diseases and disorders where the partial or total inactivation of adenosine A<sb>2A</sb> receptors signalling pathways could be beneficial such as Alzheimer's disease, Parkinson's disease, attention deficit and hyperactivity disorders (ADHD), Huntington's disease, neuroprotection, schizophrenia, anxiety and pain. The present invention further relates to pharmaceutical compositions containing such new compounds with high affinity for adenosine A<sb>2A</sb> receptors and their use for the treatment and/or prophylaxis of diseases and disorders where the partial or total inactivation of adenosine A<sb>2A</sb> receptors could be beneficial.
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NEW ADENOSINE RECEPTOR LIGANDS AND USES THEREOF (Fri, 25 Nov 2011)
<p id="p-0001" num="0000">The present invention provides new compounds with high affinity for adenosine A<sub>2A </sub>receptors. It also provides antagonists of adenosine A<sub>2A </sub>receptors and their use as medicaments for the treatment and/or prophylaxis of diseases and disorders where the partial or total inactivation of adenosine A<sub>2A </sub>receptors signalling pathways could be beneficial such as Alzheimer's disease, Parkinson's disease, attention deficit and hyperactivity disorders (ADHD), Huntington's disease, neuroprotection, schizophrenia, anxiety and pain. The present invention further relates to pharmaceutical compositions containing such new compounds with high affinity for adenosine A<sub>2A </sub>receptors and their use for the treatment and/or prophylaxis of diseases and disorders where the partial or total inactivation of adenosine A<sub>2A </sub>receptors could be beneficial</p>
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Di-Vanilloyl And Tri-Vanilloyl Derivatives For Use In Anti-Cancer Therapy (Fri, 18 Nov 2011)
<p id="p-0001" num="0000">The invention relates to the medical field, more precisely in the field of anti-cancer treatment and treatment of Alzheimer's disease, Parkinson's disease or Pick's disease or for ameliorating symptoms of Down syndrome, providing newly synthesised multi-vanilloyl derivative compounds and their use in the treatment of said disorders.</p>
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THERAPEUTIC AGENTS USEFUL FOR TREATING PAIN (Fri, 18 Nov 2011)
<p id="p-0001" num="0000">A compound of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.77mm" wi="19.47mm" file="US20110281885A1-20111117-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A, Ar, R<sup>3</sup>, R<sup>6</sup>, and m are disclosed herein, or a pharmaceutically acceptable salt thereof (a “Cyanoiminopiperazine Compound”), compositions comprising an effective amount of a Cyanoiminopiperazine Compound, and methods for treating or preventing pain, urinary incontinence, an ulcer, inflammatory-bowel disease, irritable-bowel syndrome, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Cyanoiminopiperazine Compound are disclosed.</p>
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HEMIFUMARATE SALT (Fri, 18 Nov 2011)
<p id="p-0001" num="0000">The present invention relates to a hemifumarate salt of the compound (1S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine, Form A thereof and its pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Downs 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 Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer 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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(+)-3-HYDROXYMORPHINAN-BASED POLYCYCLE DERIVATIVES AS NEUROPROTECTANTS (Fri, 18 Nov 2011)
A (+)-3-hydroxymorphinan-based polycycle derivative of formula (I) is effective as a neuroprotective agent for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and ischemic stroke.
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NOVEL HEMIFUMARATE SALT OF ISOINDOLE COMPOUND ACTING AS BACE INHIBITOR (Fri, 18 Nov 2011)
The present invention relates to a hemifumarate salt of the compound (1S)-1-(2- (difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine, Form A thereof and its pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Αβ-related pathologies such as Downs 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 Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer 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.
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AZA-INDOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 11 Nov 2011)
The present invention is directed to certain Aza-Indole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.
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AZA-INDOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 11 Nov 2011)
The present invention is directed to certain Aza-Indole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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Imidazole derivatives useful as inhibitors of FAAH (Fri, 04 Nov 2011)
<p id="p-0001" num="0000">The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. 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 metasteses, gastrointestinal stromal tumors, and giant cell tumors.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 28 Oct 2011)
Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. 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 arthiritis, 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 metasteses, gastrointestinal stromal tumors, and giant cell tumors.
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 28 Oct 2011)
The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 28 Oct 2011)
The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 28 Oct 2011)
Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. 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 arthiritis, 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 metasteses, gastrointestinal stromal tumors, and giant cell tumors.</p>
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COMPOUNDS USEFUL AS FAAH MODULATORS AND USES THEREOF (Fri, 21 Oct 2011)
<p id="p-0001" num="0000">Compounds are disclosed that have formula I: where A, B, L<sup>1</sup>, W, Y, R<sup>1</sup>, and R<sup>3 </sup>are as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, anxiety, depression, inflammation, cognitive disorders, weight and eating disorders, Parkinson's disease, Alzheimer's disease, spasticity, addiction, glaucoma, and others.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="55.12mm" file="US20110257208A1-20111020-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2-ALKOXY-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF (Fri, 21 Oct 2011)
The invention features 2-alkoxy-l l-hydroxyaporphine derivatives that selectively bind D2high receptors. The compounds are useful for imaging D2high receptors and for the treatment of diseases, such as Parkinson's disease, sexual dysfunction, and depressive disorders.
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PROCESS FOR THE PREPARATION OF (6S)-(-)-5,6,7,8-TETRAHYDRO-6-[PROPYL-(2-THIENYL)ETHYL]AMINO-1-NAPHTHOL (ROTIGOTINE) (Thu, 20 Oct 2011)
The present invention describes a novel process for the preparation of (6S)-(-)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) comprising: (a) acetylating (S)-(-)-5-hydroxy-N-n-propyl-2-aminotetraline to afford the acetate; (b) reacting this acetate, (-)-5-acetoxy- N-n-propyl-2-aminotetraline, with 2-(2-thienyl)ethanol 2- nitrobenzenesulfonate; (d) hydrolyzing (6S)-(-)-1-acetoxy-5, 6,7,8- tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthalene to afford (6S)-(- )-5, 6, 7, 8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) and (d) purifying rotigotine either by the acetylation reaction and subsequent hydrolysis of the formed acetate or by salification of rotigotine through hydrochloride or hydrobromide formation and subsequent base release. Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.
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MONOHYDRATE OF PARDOPRUNOX (Fri, 14 Oct 2011)
<p id="p-0001" num="0000">This invention relates to a process for the preparation of 7-(4-methyl-1-piperazinyl)benzoxazol-2(3H)-one hydrochloride, a partial dopamine-D<sub>2 </sub>receptor agonist and a full serotonin 5-HT<sub>1A </sub>receptor agonist.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="71.80mm" file="US20110251214A1-20111013-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">This invention also relates to the monohydrate of said compound, as well as to pharmaceutical compositions containing these compounds, to methods for preparing these compounds, to methods for preparing intermediates useful for their synthesis, and to methods for preparing compositions containing these compounds. Embodiments of the invention also relate to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in conditions or diseases of the central nervous system, caused by disturbances of the dopaminergic and/or serotonergic systems, for example: anxiety disorders (including generalized anxiety, panic disorder and obsessive compulsive disorder), depression, autism, schizophrenia, Parkinson's disease, restless leg syndrome, and disturbances of cognition and memory.</p>
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 14 Oct 2011)
The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.
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OXAZOLE DERIVATIVES USEFUL AS MODULATORS OF FAAH (Fri, 14 Oct 2011)
The present invention is directed to certain Oxazole derivatives which are useful as modulators of Fatty Acid Amide Hydrolase (FAAH) and as FAAH imaging agents. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer Disease, and Parkinson's Disease.</p>
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CHEMICAL COMPOUNDS (Fri, 30 Sep 2011)
The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I wherein R1, R2 and R3 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. 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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CHEMICAL COMPOUNDS (Fri, 30 Sep 2011)
The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I wherein R1, R2 and R3 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.</p>
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NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS (Fri, 23 Sep 2011)
The invention provides novel nicotinic acetylcholine receptor agonists, for example, phaiitasmidine and derivatives thereof, for example a compound of formula (I). Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acet lcholine rece tor a onists.
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PYRIMIDINES AND PYRIDINES USEFUL AS INHIBITORS OF PROTEIN KINASES (Fri, 16 Sep 2011)
<p id="p-0001" num="0000">The present invention relates to compounds useful as inhibitors of protein kinases, such as inhibitors of GSK-3. The invention provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders. The invention provides processes for preparing compounds of the invention. The invention provides methods of identifying compounds useful for treatment of diabetes, diabetic neuropathy, osteoporosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, AIDS-associated dementia, bipolar disorder, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, leukocytopenia, cardiomyocyte hypertrophy, stroke, post-stroke, spinal cord injury, traumatic brain injury, Charcot-Marie-Tooth, peripheral nerve regeneration, and rheumatoid arthritis.</p>
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METHOD FOR PRODUCING COMPOUND FOR PREPARATION OF ANTI-PARKINSON'S DISEASE DRUG (Fri, 09 Sep 2011)
<p id="p-0001" num="0000">The present invention provides a method for producing a compound of formula (I), which is used for preparing anti-Parkinson's disease drugs, rasagiline and rasagiline mesylate.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.94mm" wi="55.46mm" file="US20110218361A1-20110908-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Inhibitors of polo-like kinase (Fri, 02 Sep 2011)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="61.81mm" file="US08445503-20130521-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a salt or solvate thereof, wherein ring A, X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6 </sup>are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease. </p>
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Inhibitors of polo-like kinase (Fri, 26 Aug 2011)
<p id="p-0001" num="0000">The present invention provides compounds having a structure according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="55.29mm" file="US08541418-20130924-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a salt or solvate thereof, wherein ring A, E<sup>1</sup>, E<sup>2</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease. </p>
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HETEROCYCLES AS POTASSIUM CHANNEL MODULATORS (Fri, 26 Aug 2011)
Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltage- dependent potassium channels. More particularly, the invention provides heterocycles, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, seizure, retinal degeneration, hearing and vision loss, Alzheimer's disease, age- related memory loss, learning deficiencies, anxiety, neuronal degeneration and motor neuron diseases, maintaining bladder control or treating urinary incontinence) and as neuroprotective agents (e.g., to prevent stroke and the like) by modulating potassium channels associated with the onset or recurrence of the indicated conditions.
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HETEROCYCLES AS POTASSIUM CHANNEL MODULATORS (Fri, 26 Aug 2011)
Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltage- dependent potassium channels. More particularly, the invention provides heterocycles, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, seizure, retinal degeneration, hearing and vision loss, Alzheimer's disease, age- related memory loss, learning deficiencies, anxiety, neuronal degeneration and motor neuron diseases, maintaining bladder control or treating urinary incontinence) and as neuroprotective agents (e.g., to prevent stroke and the like) by modulating potassium channels associated with the onset or recurrence of the indicated conditions.</p>
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PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF PAIN AND OTHER INDICATONS (Fri, 05 Aug 2011)
The present invention is directed to a composition useful for the treatment of a FAAH mediated disease, disorder or conditions comprising a FAAH inhibitor and a second activation, comprising a selected imidazole or oxazole FAAH inhibitor and a second active agent. The compositions will be useful in the treatment of a wide range of disease, disorder, or conditions including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease. In another aspect the invention discloses herein is directed to compositions useful in the treatment of neuropathic and nociceptive pain, said compositions comprising etoricoxib.
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PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF PAIN AND OTHER INDICATIONS (Fri, 05 Aug 2011)
The present invention is directed to a composition useful for the treatment of a FAAH mediated disease, disorder or conditions comprising a FAAH inhibitor and a second activation, comprising a selected imidazole or oxazole FAAH inhibitor and a second active agent. The compositions will be useful in the treatment of a wide range of disease, disorder, or conditions including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease. In another aspect the invention discloses herein is directed to compositions useful in the treatment of neuropathic and nociceptive pain, said compositions comprising etoricoxib.</p>
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SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF (Thu, 04 Aug 2011)
The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT 6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT 6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity. In the general formula 1: wherein: X = S, SO or NH; R 1 represents hydrogen, optionally substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R 2 represents hydrogen, halogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R 3 represents hydrogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X = S or X = NH, at least one of R 1 , R 2 or R 3 represent substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R 1 , R 2 or R 3 represent hydrogen; R 4 represents C 1 -C 3 alkyl; R 5 represents hydrogen, one or two halogens, C 1 -C 3 alkyl or optionally substituted hydroxyl.
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SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF (Fri, 22 Jul 2011)
<p id="p-0001" num="0000">The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT<sub>6 </sub>receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT<sub>6 </sub>receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity.</p> <p id="p-0002" num="0000">In the general formula 1:</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.00mm" wi="60.45mm" file="US20110178078A1-20110721-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein: X═S, SO or NH; R<sup>1 </sup>represents hydrogen, optionally substituted C<sub>1</sub>-C<sub>3</sub>alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R<sup>2 </sup>represents hydrogen, halogen, optionally substituted C<sub>1</sub>-C<sub>3</sub>alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R<sup>3 </sup>represents hydrogen, optionally substituted C<sub>1</sub>-C<sub>3</sub>alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X═S or X═NH, at least one of R<sup>1</sup>, R<sup>2 </sup>or R<sup>3 </sup>represent substituted C<sub>1</sub>-C<sub>3</sub>alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R<sup>1</sup>, R<sup>2 </sup>or R<sup>3 </sup>represent hydrogen; R<sup>4 </sup>represents C<sub>1</sub>-C<sub>3</sub>alkyl; R<sup>5 </sup>represents hydrogen, one or two halogens, C<sub>1</sub>-C<sub>3</sub>alkyl or optionally substituted hydroxyl.</p>
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7-piperidinoalkyl-3, 4-Dihydroquinolone derivative (Fri, 22 Jul 2011)
<p id="p-0001" num="0000">PROBLEM</p> <p id="p-0002" num="0000">To provide a novel compound, a pharmaceutically acceptable salt or a hydrate thereof useful for preventing or treating for depression, anxiety disorders (such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder or social anxiety disorder), attention deficit disorder, mania, manic-depressive illness, schizophrenia, mood disorders, stress, sleep disorders, attacks, memory impairment, cognitive impairment, dementia, amnesia, delirium, obesity, eating disorder, appetite disorder, hyperphagia, bulimia, cibophobia, diabetes, cardiovascular diseases, hypertension, dyslipidemia, myocardial infarction, movement disorder (such as Parkinson's disease, epilepsy, convulsion or tremor), drug abuse, drug addiction or sexual dysfunction, based on a melanin-concentrating hormone receptor (MCH receptor) antagonistic action.</p> <p id="p-0003" num="0000">SOLUTION</p> <p id="p-0004" num="0000">A compound, a pharmaceutically acceptable salt or a hydrate thereof represented by the formula (I).</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.87mm" wi="76.20mm" file="US08461182-20130611-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Use of indole derivatives as NURR-1 activators for treating parkinson's disease (Fri, 22 Jul 2011)
<p id="p-0001" num="0000">The present invention relates to a compound derived from indole, especially a therapeutically useful compound, characterized in that it is selected from compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.90mm" wi="63.16mm" file="US08575210-20131105-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">in which</li> <li id="ul0002-0002" num="0000">R<sub>1 </sub>represents a halogen or a trifluoromethyl group,</li> <li id="ul0002-0003" num="0000">R<sub>2 </sub>represents a hydrogen atom or a C<sub>1</sub>-C<sub>4 </sub>alkyl group,</li> <li id="ul0002-0004" num="0000">R<sub>3 </sub>represents an isopropyl (1-methylethyl) group or a tert-butyl (1,1-dimethylethyl) group and</li> <li id="ul0002-0005" num="0000">n=3 or 4</li> <li id="ul0002-0006" num="0000">and <br/> pharmaceutically acceptable salts of said compounds of formula (I). <br/> Application: Treatment of neurodegenerative diseases and more particularly of Parkinson's disease. </li> </ul> </li> </ul> </p>
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PYRROLIDINE DERIVATIVES (Fri, 22 Jul 2011)
The present invention relates to compounds of formula (I) or to a pharmaceutically active salt thereof. It has been found that the present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).
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PYRROLIDINE DERIVATIVES (Fri, 22 Jul 2011)
The present invention relates to compounds of formula (I) or to a pharmaceutically active salt thereof. It has been found that the present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).</p>
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7-PIPERIDINOALKYL-3,4-DIHYDROQUINOLONE DERIVATIVE (Thu, 21 Jul 2011)
To provide a novel compound, a pharmaceutically acceptable salt or a hydrate thereof useful for preventing or treating for depression, anxiety disorders (such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder or social anxiety disorder), attention deficit disorder, mania, manic-depressive illness, schizophrenia, mood disorders, stress, sleep disorders, attacks, memory impairment, cognitive impairment, dementia, amnesia, delirium, obesity, eating disorder, appetite disorder, hyperphagia, bulimia, cibophobia, diabetes, cardiovascular diseases, hypertension, dyslipidemia, myocardial infarction, movement disorder (such as Parkinson's disease, epilepsy, convulsion or tremor), drug abuse, drug addiction or sexual dysfunction, based on a melanin-concentrating hormone receptor (MCH receptor) antagonistic action. SOLUTION A compound, a pharmaceutically acceptable salt or a hydrate thereof represented by the formula (I).
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Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes and parkinson's disease (Fri, 15 Jul 2011)
<p id="p-0001" num="0000">Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.</p>
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SULPHATED DISACCHARIDES FOR THE TREATMENT OF NEURODEGENERATIVE AND/OR NEUROVASCULAR DISEASES (Fri, 08 Jul 2011)
The present invention relates to the use of a series of sulphated disaccharides for the preparation of a medicament for the treatment or prevention of a neurodegenerative and/or neurovascular disease, of a traumatic brain injury or of a traumatic spinal cord injury. The present invention also relates to the use of said sulphated disaccharides for the preparation of a neuroprotective medicament or of an antioxidant medicament. The neurodegenerative and/or neurovascular diseases are preferably: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke.
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SULPHATED DISACCHARIDES FOR THE TREATMENT OF NEURODEGENERATIVE AND/OR NEUROVASCULAR DISEASES (Fri, 08 Jul 2011)
The present invention relates to the use of a series of sulphated disaccharides for the preparation of a medicament for the treatment or prevention of a neurodegenerative and/or neurovascular disease, of a traumatic brain injury or of a traumatic spinal cord injury. The present invention also relates to the use of said sulphated disaccharides for the preparation of a neuroprotective medicament or of an antioxidant medicament. The neurodegenerative and/or neurovascular diseases are preferably: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke.</p>
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DIARYL-SUBSTITUTED FIVE-MEMBERED HETEROCYCLE DERIVATIVE (Fri, 01 Jul 2011)
<p id="p-0001" num="0000">The present invention provides the compounds represented by formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.55mm" wi="69.85mm" file="US20110160208A1-20110630-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutical salts thereof, wherein: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">X<sub>1 </sub>represents oxygen atoms and the like, X<sub>2 </sub>represents nitrogen atoms and the like, X<sub>3 </sub>represents nitrogen atoms and the like, X<sub>4 </sub>represents nitrogen atoms and the like, R<sup>1 </sup>represents formula (II-1):</li> </ul> </li> </ul> </p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="16.59mm" wi="70.02mm" file="US20110160208A1-20110630-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0003" list-style="none"> <li id="ul0003-0001" num="0000"> <ul id="ul0004" list-style="none"> <li id="ul0004-0001" num="0000">wherein X<sub>5 </sub>represents sulfur atoms and the like, A<sub>1 </sub>represents carbon atoms and the like, A<sub>2 </sub>represents nitrogen atoms and the like and A ring represents phenyl group and the like,</li> <li id="ul0004-0002" num="0000">having mGluR1 inhibiting effect, and being useful for preventing or treating convulsion, acute pain, inflammatory pain, chronic pain, brain disorder such as cerebral infarction or transient ischemick attack, psychotic disorder such as schizophrenia, anxiety, drug dependence, Parkinson's disease, or gastrointestinal disorder.</li> </ul> </li> </ul> </p>
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PTERIDINONES AS INHIBITORS OF POLO-LIKE KINASE (Fri, 01 Jul 2011)
The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E1, E2, R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE (Fri, 01 Jul 2011)
The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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PTERIDINONES AS INHIBITORS OF POLO-LIKE KINASE (Fri, 01 Jul 2011)
The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E1, E2, R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.</p>
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Dopamine transporter inhibitors for use in treatment of movement disorders and other CNS indications (Thu, 30 Jun 2011)
The invention provides a class of dopamine transporter inhibitors of formula (I) (DAT inhibitors), packaged pharmaceuticals comprising such inhibitors, and their uses in treating, or the manufacturing medicaments for treating disease conditions, inlcuding Parlcinsora's disease, Hoehn and Yahr Staging of Parkinson's Disease, Unified Parkinson Disease Rating Scale (UPDRS), and Schwab and England Activities of Daily Living Scale. Related business methods such as marketing the inhibitors to healthcare providers are also provided.
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1,2,4-triazolo[4,3-c]pyrimidin-3-one and pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-3-one compounds for use as adenosine A<sub>2a </sub>receptor antagonists (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">Compounds of the Formula I wherein R<sup>1 </sup>and R<sup>2 </sup>together with the carbon atoms to which they are bonded optionally form a further heteroaromatic ring of the formula (II) as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="51.73mm" wi="55.37mm" file="US08222259-20120717-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Sigma ligands for neuronal regeneration and functional recovery (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferable AGY-94806, or salts or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by ischemic stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Huntington's disease, or Parkinson's disease. In other methods, the sigma receptor ligands are administered after stroke to facilitate functional recovery. The administration of the sigma receptor ligands effects functional recovery.</p>
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Process for the preparation of optically active (S)-(−)-2-(N-propylamino)-5-methoxytetraline and (S)-(−)-2-(N-propylamino)-5-hydroxytetraline compounds (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">The present invention describes a novel process for the preparation of optically active (S)-(−)-2-(N-propylamino)-5-methoxytetraline and (S)-(−)-2-(N-propylamino)-5-hydroxytetraline compounds based on the optical resolution of mixtures of the enantiomers of 2-(N-propylamino)-5-methoxytetraline and 2-(N-propylamino)-5-hydroxytetraline respectively. This process comprises (a) reacting a mixture of the enantiomers of said compounds with an optically active organic acid to form diastereoisomeric salts and separating the salts by crystallization. Said compounds are useful in the preparation of (6S)-(−)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine). Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.</p>
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Arylvinylazacycloalkane compounds and methods of preparation and use thereof (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">Novel vinylazacycloalkane compounds of Formula (I) are disclosed. The compounds are ligands of various nAChRs. The compounds and their pharmaceutically acceptable salts can be used to prepare pharmaceutical compositions and/or medicaments intended to prevent or treat disorders associated with dysfunction of nAChRs, especially within the central nervous system or the gastrointestinal system. Examples of types of disorders that can be treated include neurodegenerative disorders, including central nervous system disorders such as Alzheimer's disease, cognitive disorders, motor disorders such as Parkinson's disease, drug addiction, behavioral disorders and inflammatory disorders within the gastrointestinal system. The compounds can also serve as analgesics in the treatment of acute, chronic or recurrent pain.</p>
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