Abstract: The present invention provides compositions and methods for the treatment of drug-tolerant glioblastoma, and in particular glioblastoma stem cells. Specifically, the methods comprise contacting a glioblastoma stem cell with a platelet-derived growth factor receptor alpha inhibitor and one or more of a histone lysine demethylase inhibitor and a Notch inhibitor.

Abstract: The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (insert Formula I structure) wherein variables W, X, Y, R2, R2?, R3, R4, R5, R6, and R7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to beta amyloid (A?) plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.

Abstract: A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

Abstract: The invention refers to the use of Reverse Transcriptase (RT) inhibitor compounds for the preparation of pharmaceutical compositions to counteract the loss of cellular differentiation in tumour and non tumour pathologies, said compound being able to bind the hydrophobic pocket on the RT subunit p66. Particularly preferred for such uses are the following compounds: nevirapine, efavirenz, delavirdine, corresponding salts and/or pharmaceutically acceptable derivatives thereof.

Abstract: The present disclosure relates to compositions comprising impurities (e.g., carbamate and/or hydrolysis products) in a lomitapide sample and methods of detecting such impurities.

Abstract: Provided herein are compounds that exhibit activity as acetyl-CoA carboxylase modulators (e.g., inhibitors) and are useful, for example, in methods for the control of fungal pathogens in plants.

Abstract: The present invention is directed to piperidine isoxazole and isothiazole orexin compounds which are antagonists of orexin receptors. Such compounds are of the general structural formula I: wherein the variables are defined herein. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

Abstract: Provided are compounds for the treatment of neurological diseases or injuries, including neurodegenerative diseases, stroke, trauma, epilepsy, acute and chronic kidney injuries, diabetes mellitus, and/or seizures. In some embodiments, derivatives of vitamin K are provided.

Abstract: Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.

Abstract: Compounds of the form In which Q is selected from —CH?NR12, —W, —CH2NHR13, —CH?O and —CH(OR17)2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.

Abstract: Methods of treating bacterial infection by in a subject by administering a pharmaceutical composition including a celecoxib derivative are described. The compounds are particularly useful for treating infection by bacteria capable of growing inside macrophages, such as Myocobacteria tuberculosis.

Abstract: The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, each of R1 and R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

Abstract: Compounds of the form In which Q is selected from —CH?NR12, —W, —CH2NHR13, —CH?O and —CH(OR17)2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.

Abstract: The invention relates to novel oxazine derivatives of formula (I), and pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, combinations thereof, and their use as medicaments, particularly for the treatment of Alzheimer's Disease or diabetes via inhibition of BACE-1 or BACE-2.

Abstract: The present invention provides 4-(3-Amino-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: The present invention provides spiro-[1,3]-oxazines and spiro-[1,4]-oxazepines of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: The present invention provides compounds of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes. The invention further provides a radio-labelled derivative thereof.

Abstract: Provided herein is a compound of formula I: as wells as a pharmaceutical composition, a process of making and a method of using a compound of formula I. The compounds of formula I are BACE1 inhibitors useful for the treatement of, for example, Alzheimer's Disease.

Abstract: The present invention relates to novel 1-methyl-pyrazole(thio)indanyl carboxamides, to processes for preparing these compounds, to compositions comprising these compounds, and to the use thereof as biologically active compounds, especially for control of harmful microorganisms in crop protection and in the protection of materials.

Abstract: Compounds of Formula (I) and methods for inhibiting kinases, including spleen tyrosine kinases, are disclosed. Also disclosed are methods for treating a kinase-mediated disease or condition by administering to a subject a therapeutically effective amount of the compound of Formula (I).

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Abstract: The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-? proteins. A compound of the formula (I): wherein R1, R2a, R2b, R3, R4a, R4b, ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.

Abstract: The present invention relates to pyrrolopyridinone derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

Abstract: The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt or a solvate thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The present invention provides compounds of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

Abstract: The present invention relates to compounds defined by formula I: wherein the variables A1, A2, Cy1 Cy2, Cy3, E, R1a, R1b, R2, R3, n, and Q are as defined herein, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of 11 ?-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity, and dyslipidemia.

Abstract: Pharmaceutical compositions for treating Alzheimer's disease are disclosed. The pharmaceutical compositions include a compound having the general formula: and a pharmaceutically acceptable carrier. Methods for treating Alzheimer's disease, inhibiting ATase I and/or ATase 2, reducing the activity of BACE1, reducing the level of amyloid ?-peptide (A?), and/or reducing the level of APP intracellular domain peptide (AICD) by administering such compositions are also disclosed.

Abstract: The present invention relates to ethynyl derivatives of formula I wherein U, V, Y, R1, R2, R2?, R3, R3? and R8 are described herein. It has been found that the compounds of general formula I are allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention regards compositions and methods for the modulation of amidases capable of hydrolysing N-acylethanolamines useable in the therapy of inflammatory diseases. In particular, the present invention regards a compound of general formula (I): enantiomers, diastereoisomers, racemes and mixtures, polymorphs, salts, solvates thereof, wherein: (a) R is a linear alkyl radical having 13 to 19 carbon atoms or alkenyl radical having 13 to 19 carbon atoms carrying a double bond; (b) X is 0 or S; (c) Y is a 2 or 3 carbon atom alkylene residue, optionally substituted with one or two groups equal or different from each other and selected from among the group consisting of: —CH3, —CH2OH, —COOCH3, —COOH. Y may preferably be: —CH2—CH2—, —CH2—CH2—CH2—, CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2—C(CH3)2—, —CH2—CH(CH2OH)—, —CH2—C((CH2OH)2)—, —CH?CH—, —CH2—CH(COOCH3)—, —CH2—CH(COOH)—, for use as a medicine.

Abstract: A compound represented by the following formula (I) or a salt thereof: wherein R represents a hydrogen atom, a hydroxy group, or a halogen atom Ar1 represents a bicyclic heterocyclic group represented by the following formula: ?and Ar2 represents a bicyclic heterocyclic group represented by the following formulae:

Abstract: The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: Compounds of the formula I in which R1, R2 and R4 have the meanings indicated in Claim 1, are inhibitors of Syk, and can be employed, inter alia, for the treatment of cancer, rheumatoid arthritis and/or systemic lupus

Abstract: The present application describes modulators of chemokine receptor activity of formula I or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed.

Abstract: The invention relates to novel heterocyclic compounds of the formula in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their medical use and to medicaments comprising them.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. Values for the variables of Formula (I) are defined herein.

Abstract: The present invention is related to a compound of formula (I), wherein A is a nonaromatic heterocyclic ring, Ar is either absent or phenylene; ? is a radical of formula (II), R2 is a hydrophobic moiety; and G is a radical containing one or more moieties selected from the group consisting of NH, OH and a basic moiety. The compounds are inhibitors of integrins, especially antagonists of the fibronectin receptor alpha5beta1, useful as anti-angiogenic agents.

Abstract: Disclosed are compounds represented by Formula (I): or pharmaceutically acceptable salts, enantiomers or diastereomers thereof. Also disclosed are pharmaceutical compositions comprising the compounds of Formula (I) or pharmaceutically acceptable salts, enantiomers or diastereomers thereof for the therapeutic treatment of diseases associated with the modulation or inhibition of 11?-HSD1 in mammals. Values for the variables of Formula (I) are defined herein.

Abstract: Compounds of the formula (I), in which R1, R2, R3, R4, R4?, have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumors.

Abstract: The present invention relates to the preparation of poly(amino oxalate) (PAOX) using oxalyl chloride, 1,4-cyclohexanedimethanol, and piperazinediethanol, the preparation of biodegradable polymer particles using the PAOX, and the use of PAOX particles as a drug delivery vehicle. The PAOX according to the present invention is a polymer that has three characteristics of biodegradability, biocompatibility, and cationic properties at the same time with appropriate hydrophobicity and thus can be prepared as particles that allow rapid drug release. Moreover, the particles improve the delivery efficiency of a drug into cells and thus can be efficiently used as a drug delivery vehicle for the treatment of acute inflammatory diseases such as acute liver failure and acute lung injury.

Abstract: Compounds of the form In which Q is selected from —CH?NR12, —W, —CH2NHR13, —CH?O and —CH(OR17)2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.

Abstract: 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, 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.

Abstract: New compositions for and methods of treating ocular hypertension provide for effective treatment of ocular hypertension often using reduced concentrations of active components. Such compositions include a timolol component and a hypotensive lipid component. The present compositions and methods are relatively straightforward, can be easily produced, for example, using conventional manufacturing techniques, and can be easily and conveniently practiced, for example, using application or administration techniques or methodologies which are substantially similar to those employed with prior compositions used to treat ocular hypertension.

Abstract: This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions and ophthalmic diseases, disorders and conditions.

Abstract: The present application discloses compounds of formula (I) wherein X is ?O, ?S, ?NH, ?NOH and ?NO-Me; A is —C(?O)—, —S(?O)2—, —C(?S)— and P(?O)(R5)—; B is, —O—, —(CH2)3-6—, and O—(CH2)2-5—; D is, —O—, —CR7R8— and —NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: A pharmaceutical composition for treating Alzheimer's disease containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene, etc.; X is S, O, or NR1; R1 is a hydrogen atom or lower alkyl; R2, R2b, R3a, R3b, R4a and R4b are each independently a hydrogen atom, halogen, hydroxy, etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 1 to 3; and R5 is a hydrogen atom, optionally substituted lower alkyl, etc.; its pharmaceutically acceptable salt, or a solvate thereof as an active ingredient.

Abstract: The invention relates to novel 6-difluoromethyl-5,6-dihydro-2H-[1,4]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.

Abstract: This invention relates to novel substituted 5-(1-benzothiophen-2-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives of formula (I) wherein R1 is hydrogen, chloro, methyl or methoxy, R2 is hydrogen or methoxy, with the proviso that at least one of R1 and R2 is other than hydrogen, G1 represents chloro, (C1-C4)-alkyl, (C1-C4)-alkoxycarbonyl, 5-membered aza-heteroaryl, or the group —CH2—OR3, —CH2—NR4R5 or —C(?O)—NR4R6, and G2 represents chloro, cyano, (C1-C4)-alkyl, or the group —CR8AR8B—OH, —CH2—NR2R10, —C(?O)—NR11R12 or —CH2—OR15, having protein tyrosine kinase inhibitory activities, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating proliferative disorders, in particular cancer and tumor diseases.