Abstract

The present invention pertains to an enzyme preparation obtained from e-beam irradiated animal tissue, such as porcine pancreas. The present invention also pertains to methods for making such enzyme preparations, pharmaceutical compositions comprising such enzymes preparations, and methods for using such pharmaceutical compositions and enzyme preparations.

IPC Classes  ?

• C12N 9/94 - Pancreatin
• A61K 38/46 - Hydrolases (3)
• A61K 38/54 - Mixtures of enzymes or proenzymes covered by more than a single one of groups or
• A61L 2/08 - Radiation

Abstract

The present invention pertains to an enzyme preparation obtained from e-beam irradiated animal tissue, such as porcine pancreas. The present invention also pertains to methods for making such enzyme preparations, pharmaceutical compositions comprising such enzymes preparations, and methods for using such pharmaceutical compositions and enzyme preparations.

IPC Classes  ?

• A61K 38/54 - Mixtures of enzymes or proenzymes covered by more than a single one of groups or
• A61L 2/08 - Radiation
• C12N 9/94 - Pancreatin
• A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Abstract

Processes are described for producing solid or semi-solid compositions, in particular solid oral compositions for pharmaceutical use, comprising treating an enzyme or enzyme-mixture with lipase-activity and a surfactant-component at defined process parameters. Said processes are suited for diminishing undesired biological contamination, e.g. viral contamination, of the said enzyme or enzyme-mixture while maintaining its desired biological activities, e.g. enzymatic activities. The process is suitable for industrial use. Also described are solid or semi-solid compositions comprising an enzyme or enzyme-mixture having lipase activity, a surfactant-component and a polymeric additive, optionally comprising further auxiliaries. Said compositions can preferably be obtained by the processes as described herein. Further described are pharmaceutical compositions comprising the solid or semi-solid compositions as described herein.

IPC Classes  ?

• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• A61K 9/20 - Pills, lozenges or tablets
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
• A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Abstract

A method of producing an emulsion and an extrudate for a powdered nutritional product is provided. The method includes utilizing an extruder (10) that contains a high shear element (32) positioned within the barrel of the extruder (20). The use of a high shear element (32) positioned within the barrel of the extruder (20) allows both emulsification and extrusion of the ingredients to occur within the barrel of the extruder (20). A first portion of ingredients comprising a slurry is processed by the high shear element (32) to form an emulsion. The emulsion is then combined with a second portion of ingredients and extruded to form an extrudate for the desired powdered nutritional product. In some embodiments, the high shear element (32) may comprise a shearing disc or a pair of shearing discs. The extruder (10) may comprise a single screw extruder, a twin screw extruder, or any other suitable type of extruder.

IPC Classes  ?

• A23P 1/12 - Extruding
• A23L 1/00 - Foods or foodstuffs; Their preparation or treatment (preservation thereof in general A23L 3/00)
• B01F 3/08 - Mixing, e.g. dispersing, emulsifying, according to the phases to be mixed liquids with liquids; Emulsifying

Abstract

Provided are methods of diagnosing sepsis in a patient by detecting the presence and/or amount of at least two biomarkers of sepsis or severe sepsis/ septic shock in a sample from the patient. The methods and biomarkers may be used to develop an accurate prognosis for a patient having sepsis or severe sepsis/septic shock or suspected of having sepsis or severe sepsis/septic shock, or to accurately diagnose a patient having, or suspected of having sepsis or severe sepsis/ septic shock. The methods and biomarkers may be used to identify and/ or classify a patient as a candidate for a sepsis therapy.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

Extruded nutritional powders and methods of manufacturing the extruded nutritional powders, including extruded infant nutritional powders and extruded adult nutritional powders are provided. The processes utilize an extruder that is capable of internally mixing and emulsifying protein, and optionally, a carbohydrate with fat and water into an emulsion that can be dried into a powder having equivalent fat separation and dispersibility as compared to spray dried powders.

IPC Classes  ?

• A23P 10/40 - Making free-flowing powder or instant powder, i.e. powder which is reconstituted rapidly when liquid is added
• A23L 33/00 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof
• A23L 33/115 - Fatty acids or derivatives thereofFats or oils
• A23L 33/125 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing carbohydrate syrupsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugarsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing sugar alcoholsModifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives containing starch hydrolysates
• A23L 33/17 - Amino acids, peptides or proteins
• A23P 30/20 - Extruding
• A23C 9/152 - Milk preparationsMilk powder or milk powder preparations containing additives
• A23C 11/00 - Milk substitutes, e.g. coffee whitener compositions
• A23L 2/39 - Dry compositions
• A23L 2/52 - Adding ingredients

Abstract

Extruded nutritional powders and methods of manufacturing the extruded nutritional powders, including extruded infant nutritional powders and extruded adult nutritional powders are provided. The processes utilize an extruder that is capable of internally mixing and emulsifying protein, and optionally, a carbohydrate with fat and water into an emulsion that can be dried into a powder having equivalent fat separation and dispersibility as compared to spray dried powders.

IPC Classes  ?

• A23P 1/02 - Agglomerating; Granulating; Tabletting
• A23L 2/39 - Dry compositions
• A23P 1/12 - Extruding
• A23L 1/00 - Foods or foodstuffs; Their preparation or treatment (preservation thereof in general A23L 3/00)

Abstract

Extruded nutritional powders and methods of manufacturing the extruded nutritional powders, including extruded infant nutritional powders and extruded adult nutritional powders are provided. The processes utilize an extruder that is capable of internally mixing and emulsifying protein, and optionally, a carbohydrate with fat and water into an emulsion that can be dried into a powder having equivalent fat separation and dispersibility as compared to spray dried powders.

IPC Classes  ?

• A23P 1/02 - Agglomerating; Granulating; Tabletting
• A23C 11/00 - Milk substitutes, e.g. coffee whitener compositions
• A23C 13/12 - Cream preparations
• A23L 2/39 - Dry compositions
• A23P 1/12 - Extruding

Abstract

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises subjecting to elevated temperature the compound of Formula I, the water-soluble polymeric carrier and the surfactant, to provide an extrudable semi-solid mixture; extruding the semi-solid mixture; and cooling the resulting extrudate to to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer or an immune or autoimmune disease.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 9/20 - Pills, lozenges or tablets
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 47/02 - Inorganic compounds
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers

Abstract

A formulation comprising a melt-processed solid dispersion product comprising an active agent, a pharmaceutically acceptable thermoplastic polymer of N-vinyl lactams, and a pharmaceutically acceptable polyvinyl alcohol-polyalkylene glycol graft copolymer. A method for producing said formulation.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers

Abstract

TNF-α binding proteins, including chimeric, CDR-grafted, and humanized antibodies that bind TNF-α are provided. Binding proteins have high affinity for TNF-α and neutralize TNF-α activity. A binding protein can be a full-length antibody or a TNF-α -binding portion thereof. Methods of making and methods of using the binding proteins are also described. The TNF-α binding proteins are useful for detecting TNF-α and for inhibiting TNF-α activity, including in a human subject suffering from a disease or disorder in which TNF-α activity is detrimental.

IPC Classes  ?

• C12P 21/06 - Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products

Abstract

The present invention relates to N-Phenyl-(homo)piperazinyl-benzenesulfonyl or benzenesulfonamide compounds of formula I wherein the variables have the meanings given in the claims and the description, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating diseases that respond to modulation of the serotonin 5-HT6 receptor.

IPC Classes  ?

• C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 3/04 - AnorexiantsAntiobesity agents
• C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings

Abstract

The present invention relates to benzenesulfonyl or sulfonamide compounds of formulae (IA) and (IB) wherein the variables have the meanings given in the claims and the description, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating diseases that respond to modulation of the serotonin 5-HT6 receptor.

IPC Classes  ?

• C07D 209/52 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
• C07D 211/24 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by sulfur atoms to which a second hetero atom is attached
• C07D 221/06 - Ring systems of three rings
• A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
• A61P 25/00 - Drugs for disorders of the nervous system
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine

Abstract

A curcuminoid formulation, comprising a melt-processed solid dispersion product comprising one or more curcuminoids, a nutritionally acceptable thermoplastic polymer, and a phosphatide; providing an improved oral bioavailability compared to non-formulated crystalline curcuminoid. A method for producing said formulation. A nutritional product fortified with said formulation. Said formulation for use in the treatment or prophylaxis of cancer, conditions involving an inflammatory reaction, neurological disorders, cardiovascular disease, pulmonary disease, the formation of cholesterol gallstones, and parasitic infestation.

IPC Classes  ?

• A23L 1/015 - Removal of unwanted matter, e.g. deodorisation, detoxification (A23L 1/211 takes precedence);;
• A23L 1/29 - Modifying nutritive qualities of foods; Dietetic products ( A23L 1/09 takes precedence;dietetic salt substitutes A23L 1/22)
• A23L 1/30 - containing additives (A23L 1/308 takes precedence);;
• A61K 31/12 - Ketones

Abstract

The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 471/04 - Ortho-condensed systems
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to amyloid-beta (Αβ) binding proteins. Antibodies of the inven- tion have high affinity to Αβ(20-42) globulomer or any Αβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to phenalkylamine derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such phenalkylamine derivatives, and the use of such phenalkylamine derivatives for therapeutic purposes. The phenalkylamine derivatives are GlyT1 inhibitors.

IPC Classes  ?

• C07C 311/04 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
• C07C 311/05 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
• C07C 311/10 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
• C07D 231/18 - One oxygen or sulfur atom
• C07D 233/84 - Sulfur atoms
• C07D 207/267 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
• C07D 295/03 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
• A61K 31/18 - Sulfonamides
• A61K 31/415 - 1,2-Diazoles
• A61K 31/4164 - 1,3-Diazoles
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia

Abstract

The present invention relates to aminoindane derivatives of the Formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such aminoindane deriva- tives, and the use of such aminoindane derivatives for therapeutic purposes. The aminoindane derivatives are GlyT1 inhibitors.

IPC Classes  ?

• C07C 11/10 - Alkenes with five carbon atoms
• C07C 311/14 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 231/18 - One oxygen or sulfur atom
• C07D 233/84 - Sulfur atoms
• A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
• A61K 31/415 - 1,2-Diazoles
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/18 - Sulfonamides
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
• A61P 25/22 - Anxiolytics
• A61P 25/24 - Antidepressants

Abstract

The present invention relates to tetraline and indane derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such tetraline and indane derivatives, and the use of such tetraline and indane derivatives for therapeutic purposes. The tetraline and indane derivatives are GlyT1 inhibitors.

IPC Classes  ?

• C07D 233/84 - Sulfur atoms
• C07C 311/03 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/18 - Sulfonamides
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to phenalkylamine derivatives of the formula (I) or (II); or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such phenalkylamine derivatives, and the use of such phenalkylamine derivatives for therapeutic purposes. The phenalkylamine derivatives are GlyT1 inhibitors.

IPC Classes  ?

• C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia

Abstract

The present invention relates to the identification and use of diagnostic markers for ischemic stroke of the lacunar subtype. The invention relates to devices and kits for performing these methods.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

A nanosuspension formulation comprising particles of at least one functional ingredient dispersed in a hydrophobic phase comprising a polydimethylsiloxane that can be used, e.g., in the pharmaceutical, cosmetics and food industry, in agriculture as well as for technical applications, and a method for producing said nanosuspension formulation are provided. The nanosuspension formulation of the invention can be highly concentrated, can be prepared also with poorly soluble functional ingredients and allows a gradual release of the functional ingredient into an aqueous environment which is accelerated compared to the dissolution of the functional ingredient when added as bulk material to the aqueous medium.

IPC Classes  ?

• A61K 9/107 - Emulsions
• A61K 9/113 - Multiple emulsions, e.g. oil-in-water-in-oil
• B02C 17/00 - Disintegrating by tumbling mills, i.e. mills having a container charged with the material to be disintegrated with or without special disintegrating members such as pebbles or balls
• B02C 19/06 - Jet mills

Abstract

The present application relates to aryl- and heteroaryl-fused decahydropyrroloazepine, octahydrooxepinopyrrole, octahydropyrrolothiazepine dioxide, decahydrocyclohepta[c]pyrrole, and octahydrocyclohepta[c]pyrrole derivatives of formula (I) wherein R1, R2, R3, R4, R5, A, Y1, Y2, and Y3 are as defined in the specification. The present application also relates to compositions comprising such compounds, processes for making such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

IPC Classes  ?

• A01N 43/00 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
• A01N 43/46 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom rings with more than six members
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole

Abstract

The present invention relates to amyloid-beta (As) binding proteins. Antibodies of the invention have high affinity to As(20-42) globulomer or any Aƒ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

The present invention concerns a method and a device for determining mechanical stress load, and optionally interface effects, on particles dispersed in a fluid. According to the invention, fluid comprising dispersed particles such as bio molecules is fed into a sample space of a device comprising a jacket which encloses a sample chamber and at least two rolls arranged within said jacket such that said sample space is defined between said rolls, said rolls being independently rotatable with respect to each other, wherein said jacket has an inner surface which is essentially adapted to the outer surface of the rolls, rotational movement is imparted to at least one of the rolls of said device, and changes in the state of said particles are determined from which mechanical stress load acting on the particles can be determined.

IPC Classes  ?

• G01N 1/28 - Preparing specimens for investigation

Abstract

A liquid mixture, comprising a) at least one compound selected from polyols, polyol ethers wherein at least one hydroxyl group is unetherified, or polyalkylene ethers wherein at least one terminal hydroxyl group is unetherified, b) 1,3-bis(caprolactam-1 - yl) butane, and c) diacetoxybutane mimics the solubility properties of a graft copolymer comprising a poly(alkylene glycol) backbone and a vinyl acetate/N-vinylcaprolactam copolymer grafted onto the backbone. In a method for evaluating the compatibility of a biologically active substance with the graft copolymer i) the biologically active sub- stance is brought into contact with the liquid mixture, and ii) the phase behavior of the test system and/or the solubility of the biologically active substance in the mixture is determined.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/14 - Particulate form, e.g. powders
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers

Abstract

A method for evaluating the solubility of a crystalline substance in a polymer comprises a) providing at least one sample of an intimate crystalline substance/polymer mixture at a predetermined crystalline substance concentration; b) annealing the sample at a constant temperature Ta for a period of time; c) heating the annealed sample while recording the heat flux over time by DSC; d) identifying a DSC dissolution endotherm in the recorded heat flux, if any; e) considering the crystalline substance concentration as a concentration above the crystalline substance solubility in the polymer at temperature Ta when there is a DSC dissolution endotherm identified, and considering the crystalline substance concentration as a concentration less than or equal to the crystalline substance solubility in the polymer at temperature Ta when there is no DSC dissolution endotherm identified. Thus, the method yields the upper and lower bounds for the equilibrium solubility at a given temperature or the upper and lower bounds for the equilibrium solubility temperature at a given crystalline substance concentration. The method improves accuracy of measurement near the glass transition temperature.

IPC Classes  ?

• G01N 25/48 - Investigating or analysing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation
• G01N 33/15 - Medicinal preparations

Abstract

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C1-C3-alkyl, C1-C3-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, or phenyl-C1-C3-alkyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

IPC Classes  ?

• C07D 207/28 - 2-Pyrrolidone-5- carboxylic acidsFunctional derivatives thereof, e.g. esters, nitriles
• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 27/08 - Mydriatics or cycloplegics
• A61P 35/00 - Antineoplastic agents
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 31/18 - Antivirals for RNA viruses for HIV
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R1, R2, R3 R4, R5,, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R1 is optionally substituted phenyl-C1-C2-alkyl or hetaryl-C1-C2-alkyl, R2 is optionally substituted aryl, hetaryl, aryl-C1-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C1-C4-alkyl, R3 is C3-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C2-alkyl, C3-C6- heterocycloalkyl-C1-C2-alkyl, phenyl-C1-C3-alkyl, pyridin-2-yl-C1-C3-alkyl or 1,3- benzoxazol-2-yl-methyl, R4 and R5 independently of one another are halogen, CF3, CHF2, CH2F, C1-C2-alkyl or C1-C2-alkoxy, and m and n independently of one another are 0 or 1.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present application describes RGM A binding proteins, particularly monoclonal antibodies, and in particular CDR grafted, humanized versions thereof, which have the ability to bind to RGM A and prevent binding of RGM proteins to RGM A receptor and other RGM A binding proteins, and therefore neutralize the function of RGM A, for use in the treatment of retinal nerve fiber layer (RNFL) degeneration as well as methods of therapeutically or prophylactically treating a mammal against RNFL degeneration.

IPC Classes  ?

• C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to compositions for oral administration. The invention preferably comprises at least one abuse - resistant drug delivery composition for delivering a drug having potential for dose dumping in alcohol, related methods of preparing these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compositions to the patient. The dosage form can include verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non- abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non -abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 9/14 - Particulate form, e.g. powders
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine

Abstract

A delivery system for sustained release of a calcium-channel blocking agent is adapted for introduction in the cerebrospinal fluid of a subject. The delivery system comprises a solid dispersion product of a calcium-channel blocking agent in a mixture of a (i) first poly(lactide-co-glycolide) having a molecular weight distribution centered around a first number average molecular weight Mn1 and a (ii) second poly(lactide-co- glycolide) having a molecular weight distribution centered around a second number average molecular weight Mn2, wherein Mn1 is in the range of from 2000 to 3000 g/mol and the ratio of Mn1/Mn2 is from 1.8 to 3.5. The delivery system is deposited in the vicinity of or adjacent to a blood vessel showing vasospasm or suspected of developing vasospasm.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate

Abstract

The invention provides methods of treating psoriasis in a subject by administering to a subject an antibody capable of binding to the p40 subunit of IL- 12 and/or IL-23.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to the use of substituted oxindole derivatives of formula I as defined in the claims and description for the treatment or prophylaxis of pain.

IPC Classes  ?

• A61K 31/404 - Indoles, e.g. pindolol
• C07B 59/00 - Introduction of isotopes of elements into organic compounds
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The invention relates to a pharmaceutical dosage form which comprises a solid dispersion product comprising N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-l-cyclohex-l-en- 1-yl)methyl)piperazin- 1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1- ((phenylsulfanyl)methyl) propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide or a salt, hydrate or solvate thereof, at least one pharmaceutically acceptable polymer, and at least one pharmaceutically acceptable solubilizer. The invention is further directed to processes for preparing the pharmaceutical dosage form and to use of the dosage form for treating proliferative disorders.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 9/14 - Particulate form, e.g. powders

Abstract

The present application relates to aryl- and heteroaryl-fused decahydropyrroloazepine, octahydrooxepinopyrrole, octahydropyrrolothiazepine dioxide, decahydrocyclohepta[c]pyrrole, and octahydrocyclohepta[c]pyrrole derivatives of formula (I), wherein R1, R2, R3, R4, R5, A, Y1, Y2, and Y3 are as defined in the specification. The present application also relates to compositions comprising such compounds, processes for making such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• C07D 491/04 - Ortho-condensed systems
• C07D 495/04 - Ortho-condensed systems
• A61P 25/00 - Drugs for disorders of the nervous system
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine

Abstract

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3a, R3b, R4, Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula (Ia) and (Ib) in which R1, r, R2b, R3a, R3b, R4, Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH2-CH2, CH2-CH2-CH2, N(Ry#)-CH2, N(Ry#)-CH2-CH2 or CH=CH-CH=, each optionally having 1 or 2 H-atoms replaced with identical or different radicals Ry, wherein Ry and Ry# have the meanings mentioned in the claims.

IPC Classes  ?

• C07D 207/26 - 2-Pyrrolidones
• C07D 211/76 - Oxygen atoms attached in position 2 or 6
• C07D 233/34 - Ethylene-urea
• C07D 239/10 - Oxygen or sulfur atoms
• A61K 31/4412 - Non-condensed pyridinesHydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring

Abstract

The present invention relates to N-phenyl-(piperazinyl or homopiperazinyl)- benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds,pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. wherein X is a bond or a group N-R4; R1 is hydrogen or methyl; R2 is hydrogen or methyl; R3 is hydrogen, C1-C3 alkyl, fluorine, C1-C2 alkoxy or fluorinated C1-C2 alkoxy; R4 is hydrogen, C1-C4 alkyl, C3-C4 cycloalkyl, or C3-C4 cycloalkyl-CH2-; R5 is hydrogen, fluorine, chlorine, C1-C2 alkyl, fluorinated C1-C2 alkyl, C1-C2 alkoxy or fluorinated C1-C2 alkoxy; R6 is hydrogen, fluorine or chlorine; and n is 1 or 2.

IPC Classes  ?

• C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 317/06 - Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 2 condensed with carbocyclic rings or ring systems
• C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence

Abstract

The present invention relates to novel benzenesulfonanilide compounds of the formulae I and I' and physiologically tolerated acid addition salts and the N-oxides thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. Formula (I) (I') wherein n is 1 or 2; R1 is hydrogen or methyl and is positioned vicinal to the radical R1; R2 is hydrogen or methyl; R3 is C1-C3 alkyl; R4 is hydrogen, C1-C4 alkyl, cyclopropyl, C3-C4 cycloalkylmethyl or fluorinated C1-C4 alkyl; R5 is hydrogen, fluorine, chlorine, C1-C4 alkyl, fluorinated C1-C4 alkyl, C1-C4 alkoxy or fluorinated C1-C4 alkoxy; and R6 is hydrogen, fluorine or chlorine.

IPC Classes  ?

• C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 295/135 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• A61P 3/04 - AnorexiantsAntiobesity agents
• A61P 25/00 - Drugs for disorders of the nervous system
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin

Abstract

The present invention relates to novel benzenesulfonanilide compounds of the Formulae (I) and (I') and physiologically tolerated acid addition salts and the N-oxides thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. (I) (I') F wherein R1 is hydrogen or methyl; R2 is hydrogen or methyl and is positioned vicinal to the radical R1; R3 hydrogen, C1-C3 alkyl, halogen, C1-C3 alkoxy, fluorinated C1-C3 alkyl or fluorinated C1-C3 alkoxy; R4 is hydrogen, C1-C4 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkylmethyl or fluorinated C1-C4 alkyl; R5 is hydrogen, fluorine, chlorine, C1-C4 alkyl, fluorinated C1-C4 alkyl, C1-C4 alkoxy or fluorinated C1-C4 alkoxy; and R6 is hydrogen, fluorine or chlorine.

IPC Classes  ?

• C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61P 3/00 - Drugs for disorders of the metabolism

Abstract

An orally deliverable pharmaceutical composition comprises as a sole or first active ingredient a compound of Formula I defined herein or a pharmaceutically acceptable salt thereof, for example ABT-263 free base or ABT-263 bis-HCl salt, dispersed, in a free base equivalent amount of at least about 2.5% by weight of the composition, in a pharmaceutically acceptable carrier; wherein said active ingredient is in solid-state form and/or the composition further comprises, dispersed in the carrier, a pharmaceutically acceptable heavier-chalcogen antioxidant in an amount effective to inhibit oxidation of the active ingredient at a thioether linkage thereof. The composition is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
• A61K 47/02 - Inorganic compounds
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids

Abstract

The present application relates to 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine, 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine, 2,3,4,4a,5,6,7,11b-octahydro-1H-pyrido[3,4-d][2]benzazepine, 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1]benzazepine, 1,2,3,4,4a,5-hexahydro-7H-pyrazino[1,2-a][4,1]benzoxazepine, and 2,3,4,4a,5,6-hexahydro-1H-pyrazino[2,1-d][1,5]benzoxazepine, and 5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine derivatives of formula (I) wherein R1, R2, R3, R4, R5, R6, X1, X2, X3, X4, Y1, Y2, and Y3 are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

IPC Classes  ?

• C07D 498/04 - Ortho-condensed systems
• C07D 471/04 - Ortho-condensed systems
• C07D 471/14 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems
• C07D 491/04 - Ortho-condensed systems
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to novel heterocyclic compounds of the following formula (IA) or (IB) which are useful for inhibiting glycogen synthase kinase 3 (GSK- 3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 491/04 - Ortho-condensed systems
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to novel carboxamide compounds and their use as a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity and to a method for the therapeutic and/or prophylactic treatment by administering an effective amount of at least one of these carboxamide compounds. The carboxamide compounds are compounds of the general formula (I) in which W-R2 is selected from formulae (1), (2) and (3) and R1, R2, R3a, R3b, Y1, Y2, Y3, Y4, X, Q, m, k, Rw and Rw* have the meanings mentioned in the claims, the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y1, Y2, Y3 and Y4 are CRy, or one or two of the variables Y1 to Y4 are a nitrogen atom and the remaining variables are CRy, wherein the radicals Ry may be identical or different and have the meanings mentionend in the claims.

IPC Classes  ?

• C07D 277/22 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 35/00 - Antineoplastic agents
• A61P 31/18 - Antivirals for RNA viruses for HIV

Abstract

The present invention relates to heterocyclic compounds of the formula (I) or a physiologically tolerated salt thereof. The present invention also relates to pharmaceutical compositions comprising such heterocyclic compounds, and the use of such heterocyclic compounds for the manufacture of a medicament for inhibiting the glycine transporter GIyT1.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07D 471/14 - Ortho-condensed systems
• C07D 491/04 - Ortho-condensed systems
• C07D 495/04 - Ortho-condensed systems
• C07D 498/04 - Ortho-condensed systems
• C07D 513/04 - Ortho-condensed systems
• A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61P 25/24 - Antidepressants

Abstract

The present invention relates to aminotetraline derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such aminotetraline derivatives, and the use of such aminotetraline derivatives for therapeutic purposes. The aminotetraline derivatives are GIyT1 inhibitors.

IPC Classes  ?

• C07C 215/70 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
• C07C 311/00 - Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
• C07C 317/00 - SulfonesSulfoxides
• C07C 233/00 - Carboxylic acid amides
• C07D 213/71 - Sulfur atoms to which a second hetero atom is attached
• C07D 231/18 - One oxygen or sulfur atom
• C07D 233/84 - Sulfur atoms
• C07D 249/12 - Oxygen or sulfur atoms
• C07D 261/08 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
• C07D 305/08 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms
• C07D 333/04 - Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulfur atom
• C07F 7/10 - Compounds having one or more C—Si linkages containing nitrogen
• A61K 31/16 - Amides, e.g. hydroxamic acids
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to compositions for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery composition for delivering a drug having potential for dose dumping in alcohol, related methods of preparing these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compositions to the patient. Most preferably, the dosage form includes verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release.

IPC Classes  ?

• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine
• A61K 9/20 - Pills, lozenges or tablets

Abstract

The present invention relates to relates to an amyloid ß peptide analogues comprising an amino acid sequence or a peptidomimetic thereof, wherein the sequence (i) forms a loop, (ii) has at least 66 % identity to the amino acid sequence of native Aß peptide or a portion thereof, (iii) comprises at least 6 contiguous amino acid residues and (iv) has at least 2 non-contiguous amino acid residues which are covalently linked with each other, oligomers comprising a plurality of said amyloid ß peptide analogues, processes for preparing the amyloid ß peptide analogues or oligomers, compositions comprising the amyloid ß peptide analogues or oligomers, and uses of the amyloid ß peptide analogues or oligomers such as their use for treating or preventing an amyloidosis (e.g. by active immunization), for diagnosing an amyloidosis, and for providing agents that are capable of binding to the amyloid ß peptide analogues or oligomers. The subject invention also describes agents that are capable of binding to the amyloid ß peptide analogues or oligomers, e.g. antibodies, compositions comprising the agents, and uses of the agents such as their use for treating or preventing an amyloidosis (e.g. by passive immunization) and for diagnosing an amyloidosis.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The invention relates to novel carbamate-substituted oxindole derivatives of formula (I), pharmaceuticals containing the same, and the use thereof for treating vasopressin-dependent diseases. In said formula (I), R1 represents hydrogen, methoxy, or ethoxy, R2 represents hydrogen or methoxy, R3 represents hydrogen, methyl, ethyl, n-propyl, or isopropyl, and X1 and X2 represent N or CH, provided that X1 and X2 do not simultaneously represent N.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors

Abstract

The present invention relates to an Aβ(X - 38.. 43) oligomer having a high molecular weight, or a derivative thereof, a process for preparing the oligomer or derivative, compositions comprising the oligomer or derivative, and uses of the oligomer or derivative such as its use for treating or preventing an amyloidosis (e.g. by active immunization), for diagnosing an amyloidosis, and for providing agents that are capable of binding to the Aβ(X - 38.. 43) oligomer or derivative. The subject invention also describes agents that are capable of binding to the Aβ(X - 38.. 43) oligomer or derivative, e.g. antibodies, compositions comprising the agents, and uses of the agents such as their use for treating or preventing an amyloidosis (e.g. by passive immunization) and for diagnosing an amyloidosis.

IPC Classes  ?

• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

A pharmaceutical dosage form comprises a solid dispersion product of at least one active ingredient dispersed in a polymeric binder composition, the polymeric carrier composition comprising a) a vinylpyrrolidone homopolymer, wherein at least 95 % by weight of the vinylpyrrolidone homopolymer has a molecular weight distribution within the range of from 1000 to 13 000; and b) a vinylpyrrolidone copolymer having a weight- average molecular weight of from 5000 to 1 500 000. The dosage form is preferably prepared by a melt extrusion process. The polymeric carrier composition exhibits a high drug dissolution power and allows a reduction of the viscosity of the melt without deteriorating the mechanical properties and storage stability of the dosage form.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers

Abstract

A viable strategy to enhance the bioavailability of poorly soluble drugs is to use amorphous solids in place of the more commonly used crystalline solids in pharmaceutical formulations. However, amorphous solids are physically meta-stable and tend to revert back to their crystalline counterpart. An effective approach to stabilizing an amorphous drug against crystallization is to disperse it in a polymer matrix. The drug's solubility in the chosen polymer defines the upper limit of drug loading without any risk of crystallization. Measuring the solubility of a drug in a polymer has been a scientific and technological challenge because the high viscosity of polymers makes achieving solubility equilibrium difficult and because pharmaceutically important drug/polymer dispersions are glasses, which undergo structural relaxation over time. The invention provides a method based on Differential Scanning Calorimetry (DSC) for measuring the solubility of crystalline drugs in polymeric matrices. The method relies on the detection of the dissolution endpoint of a drug/polymer mixture prepared by cryomilling.

IPC Classes  ?

• G01N 33/15 - Medicinal preparations
• G01N 25/48 - Investigating or analysing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation

Abstract

The present application relates to isolated proteins, particularly monoclonal antibodies, in particular CDR-grafted, humanized antibodies which bind to RAGE protein. Specifically, these antibodies have the ability to inhibit the binding of RAGE to its various ligands. The antibodies or portions thereof of described in the present application are useful for treating a disease or disorder characterized by or induced by pathophysiological ligands of RAGE, for example missfolded proteins like amyloid β and advanced glycation-end-products.

IPC Classes  ?

• C12N 15/12 - Genes encoding animal proteins
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof

Abstract

The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• C07D 487/08 - Bridged systems
• C07C 275/28 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
• C07C 275/32 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
• C07C 275/42 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 25/16 - Anti-Parkinson drugs
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis

Abstract

The present invention relates to tetrahydroisoquinoline of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such tetrahydroisoquinolines, and the use of such tetrahydroisoquinolines for therapeutic purposes. The tetrahydroisoquinolines are GIyT1 inhibitors.

IPC Classes  ?

• C07D 217/18 - Aralkyl radicals
• C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 498/04 - Ortho-condensed systems
• C07D 513/04 - Ortho-condensed systems
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The subject invention relates to isolated proteins, particularly monoclonal antibodies, which bind and neutralize RGM A protein. Specifically, these antibodies have the ability to inhibit the binding of RGM A to its receptor and/or coreceptors. These antibodies or portions thereof of the invention are useful for detecting RGM A and for inhibiting RGM A activity, for example in a human suffering from a disorder including but not limited to multiple sclerosis, mammalian brain trauma, spinal cord injury, stroke, neurodegenerative diseases, and schizophrenia.

IPC Classes  ?

• C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to compositions for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery composition for delivering a drug having potential for dose dumping in alcohol, related methods of preparing these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compositions to the patient. Most preferably, the dosage form includes verapamil.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil

Abstract

A method for preparing a protein or peptide powder is provided that includes spray drying a solution including more than, e.g., about 50 mg/mL of a protein or peptide (e.g., an antibody or antigen binding protion thereof), and at least one excipient. Also provided are stable powdered compositions including a protein and an excipient having less than, e.g., about 6% residual moisture.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 31/70 - CarbohydratesSugarsDerivatives thereof
• A61K 31/715 - Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkagesDerivatives thereof, e.g. ethers, esters
• A61K 38/02 - Peptides of undefined number of amino acidsDerivatives thereof
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Abstract

The present invention relates to novel substituted oxindole-derivatives of the formula (I), pharmaceutical agents containing said derivatives, and the use thereof for the treatment of vasopressin-dependent illnesses.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to novel carboxamide compounds of the formula (I) and their use for the manufacture of a medicament. The carboxamide compounds are prodrugs of inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity and the rest of the variables is as defined in the claims.

IPC Classes  ?

• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

A pharmaceutical dosage form, comprising a) a liquid or flowable core, b) a shell of a polysaccharide or proteinaceous material completely enclosing said core, the core comprising an active ingredient dissolved in a pharmaceutically acceptable compound of the formula (I) wherein n is an integer from 3 to 5, and wherein the (i) the at least one active ingredient and the compound of the formula (I) account for at least 50 % by weight of the composition; and (ii) the water activity aw of the composition is less than 0.4.

IPC Classes  ?

• A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
• A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• A61K 47/38 - CelluloseDerivatives thereof

Abstract

The present invention relates to novel substituted oxindole derivatives of formula (I), pharmaceutical agents containing them, and the use thereof for the treatment of vasopressin-dependent illnesses.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 487/04 - Ortho-condensed systems
• C07D 487/08 - Bridged systems

Abstract

The present invention relates to novel amidomethyl-substituted oxindole derivatives of formula (I), pharmaceutical agents containing same, and the use thereof for the treatment of vasopressin-dependent illnesses. In formula (I), R1 is hydrogen, methoxy or ethoxy; R2 is hydrogen or methoxy; R3 is hydrogen, methyl, ethyl, n-propyl or isopropyl; and X1 and X2 are N or CH, with the proviso that X1 and X2 are not both N at the same time.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The invention relates to novel 5-halogen-substituted oxindole-derivatives, pharmaceutical agents containing said components and to the use thereof for treating vasopressine-dependent diseases.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The invention relates to novel 5,6-disubstituted oxindole derivatives, to pharmaceutical agents containing said components and to the use thereof for producing a medicament.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The invention relates to compounds of the formula R1 is selected from the group consisting of hydrogen, linear C1-C3 alkyl and fluorinated linear C1-C3 alkyl; R2 is hydrogen or methyl; R3 is selected from the group consisting of hydrogen, halogen, C1-C2-alkyl, fluorinated C1-C2-alkyl, C1-C2-alkoxy and fluorinated C1-C2-alkoxy, R4 is C1-C2-alkyl or fluorinated C1-C2-alkyl; n is 0, 1 or 2, and the physiologically tolerated salts of these compounds and the N-oxides thereof. The invention also relates to a pharmaceutical composition that comprises at least one compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.

IPC Classes  ?

• C07D 213/76 - Nitrogen atoms to which a second hetero atom is attached
• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• A61P 25/00 - Drugs for disorders of the nervous system
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone

Abstract

The invention relates to compounds of the formula (I), wherein A is a saturated or unsaturated hydrocarbon chain having a chain length of 4 to 6 carbon atoms, the hydrocarbon chain being unsubstituted or substituted by 1, 2 or 3 methyl groups; R1 is selected from the group consisting of hydrogen, C1-C3alkyl and fluorinated C1-C3alkyl; R2 is hydrogen, halogen, cyano, C1-C3alkyl, C1-C3alkoxy, fluorinated C1-C3alkyl or fluorinated C1-C3alkoxy; R3 is selected from the group consisting of branched C4-C6alkyl and C3-C6cycloalkyl, and R4 is C1-C6alkyl, C3-C6cycloalkyl, fluorinated C1-C3alkyl and fluorinated C3-C6cycloalkyl. and the physiologically tolerated salts of these compounds and the N-oxides thereof. The invention also relates to a pharmaceutical composition that comprises at least one compound of the formula (I) and/or at least one physiologically tolerated acid addition salt thereof, and furtherto amethod for treating disorders that respond beneficially to dopamine D3receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one compound or physiologically tolerated acid addition salt of the formula (I) to a subject in need thereof.

IPC Classes  ?

• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
• A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence

Abstract

The present invention relates to novel benzenesulfonanilide compounds of the formulae I and I' and physiologically tolerated acid addition salts and the N-oxides thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. wherein R1 is hydrogen or methyl R2 is hydrogen or methyl R3 hydrogen, fluorine C1-C2 alkoxy or fluorinated C1-C2 alkoxy; R4 is hydrogen, C1-C4 alkyl or fluorinated C1-C4 alkyl; R5 is hydrogen, fluorine, C1-C2 alkyl, fluorinated C1-C2 alkyl, C1-C2 alkoxy or fluorinated C1-C2 alkoxy; and R6 is hydrogen, fluorine or chlorine.

IPC Classes  ?

• C07D 295/12 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 3/04 - AnorexiantsAntiobesity agents
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence

Abstract

A solid dispersion product comprising at least one N-aryl urea-based pharmaceutically active agent or an agent of related structural type is obtained by a) preparing a liquid mixture containing the at least one active agent, at least one pharmaceutically acceptable matrix-forming agent, at least one pharmaceutically acceptable surfactant and at least one solvent, and b) removing the solvent(s) from the liquid mixture to obtain the solid dispersion product.

IPC Classes  ?

• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol

Abstract

A solid dispersion product comprising at least one N-aryl urea-based pharmaceutically active agent is obtained by a) preparing a liquid mixture containing the at least one active agent, at least one pharmaceutically acceptable matrix-forming agent, at least one pharmaceutically acceptable surfactant and at least one solvent, and b) removing the solvent(s) from the liquid mixture to obtain the solid dispersion product.

IPC Classes  ?

• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol

Abstract

The present invention relates to the identification and use of bone morphogenetic protein (BMP)-binding domains of members of the repulsive guidance molecule (RGM) protein family, and polypeptide fragments and fusion proteins derived therefrom. The domains, i.e., peptide fragments and fusion proteins, according to the invention are suitable as agents for the active or passive immunization of individuals, or as diagnostic and therapeutic agents for use for diseases or medical conditions in whose origin or progression a member of the RGM family and a cellular receptor associated with this molecule, such as neogenin and/or BMP in particular, is involved. The invention further relates to monoclonal and polyclonal antibodies directed against the binding domains according to the invention, and against the polypeptides derived therefrom, and to methods for producing the polypeptides, fusion proteins, and antibodies according to the invention.

IPC Classes  ?

• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

The present invention relates to novel 4-(4-pyridyl)-benzamides of the formula (I). The compounds I possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs). R1 and R2 are, independently of each other, hydrogen, hydroxy, cyano, C1-C8-alkyl, C1- C8-haloalkyl, C1-C8-alkoxy or C1-C8-haloalkoxy; R3, R4, R5 and R6 are, independently of each other, hydrogen, hydroxy, halogen, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy, amino, C1-C8-alkylamino or di-(C1-C8-alkyl)-amino; R7 is hydrogen, C1-C8-alkyl, C1-C8-haloalkyl, aryl or aryl-C1-C8-alkyl; R8 is a group of the formula -X-W, where X is a single bond, C1-C4-alkylene or C1-C4-alkylene-O-, where the alkylene group in the three last-mentioned radicals may be linear or branched and may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or may be interrupted by an oxygen atom; and W is a cyclic radical selected from phenyl and a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups; R9 is a group of the formula -Y-Z, where Z is hydrogen, halogen, OR11, NR12R13, S(O)m-R14, phenyl which may carry 1, 2, 3 or 4 substituents R15 or a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring; and Y is linear or branched C1C4-alkylene which may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or a phenyl ring; or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring as defined above, Y can also be a single bond.

IPC Classes  ?

• C07D 213/56 - Amides
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 35/00 - Antineoplastic agents
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

A description is given of a process for the preparation of a pharmaceutical composition of a macrolide antibiotic in essentially noncrystalline form, in which the macrolide antibiotic, a water-swellable polymer and a proton donor are blended in an extruder in the presence of water and forced through a die, the ratio by weight of the sum of macrolide antibiotic, water-swellable polymer and proton donor to water being at least 1 :1. The macrolide antibiotic is preferably clarithromycin and the water-swellable polymer is preferably chosen from crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethylcellulose and crosslinked polyacrylic acid.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61K 31/7052 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides

Abstract

The present invention relates to 4-benzylaminoquinolines of the formula (I) or physiologically tolerated salts thereof. The invention relates to pharmaceutical compositions comprising such quinolines, and the use of such quinolines for therapeutic purposes. The quinolines are GIyTI inhibitors.

IPC Classes  ?

• C07D 251/42 - One nitrogen atom
• C07D 215/46 - Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/4706 - 4-Aminoquinolines8-Aminoquinolines, e.g. chloroquine, primaquine
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to novel quinoline compounds of the formula (I) and to the salts thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. In formula (I) R is a moiety of the formula (R) wherein * indicates the binding site to the quinolinyl radical and wherein A, B, X', Y, Q, R1, R2, R3, R4, R5, m, n, p, q, Ra, Rb, X and Ar are as defined in claim 1.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems
• C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to derivatives and metabolites of ambrisentan, including compounds of general Formula (I) or salts, hydrates, solvates, racemates, or optical isomers thereof, wherein R1 is -H or -OCH3; R2 is -H, lower alkyl (e.g. C1-C4 alkyl) or glycosidyl; and R3 and R4 are independently -CH3, -C(O)H or -CH2OR6, wherein R6 is -H or a hydrocarbyl group having 1 to 20 carbon atoms. In some embodiments, compounds of Formula (I) exhibit selective affinity for ETA receptors and serve as endothelin receptor antagonists. In some embodiments, the compounds correspond to metabolites of ambrisentan produced by the enzymatic action of cytochrome P450 or uridine diphosphate glucuronosyl transferase enzymes, for example as elucidated in pre-clinical or clinical studies.

IPC Classes  ?

• C07D 239/34 - One oxygen atom
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The preferred exemplary embodiments in the present application provide formulations and methods for the delivery of drugs, particularly drugs of abuse, having an abuse-relevant drug substantially confined in the core and a non-abuse relevant drug in a non-core region. These formulations have reduced potential for abuse. In the formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release.

IPC Classes  ?

• A61K 9/28 - DrageesCoated pills or tablets
• A61K 31/00 - Medicinal preparations containing organic active ingredients

Abstract

The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

IPC Classes  ?

• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond

Abstract

The present invention relates to binding proteins and, in particular, humanized antibodies that may be used, for example, in the diagnosis, treatment and prevention of Alzheimer's Disease and related conditions.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

The present invention relates to binding proteins and, in particular, humanized antibodies that may be used, for example, in the diagnosis, treatment and prevention of Alzheimer's Disease and related conditions.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to heterocyclic compounds which are positive modulatorsof metabotropic glutamate receptor. The present invention also relates to the use of these compounds for preparing a pharmaceutical composition and to a method of treating a medical disorder, selected from neurological and psychiatric disorders associated with glutamate dysfunction.

IPC Classes  ?

• C07D 209/26 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
• C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 333/58 - Radicals substituted by nitrogen atoms
• C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 277/28 - Radicals substituted by nitrogen atoms
• C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
• C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 333/20 - Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
• C07D 307/14 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
• C07D 213/36 - Radicals substituted by singly-bound nitrogen atoms
• C07D 213/38 - Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom

Abstract

The present invention relates to novel quinoline compounds. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. formula (I) wherein R is a moiety of the formula (R) wherein A, R1 to R4 are as defined in the claims and the specification, n is 0, 1 or 2; m is 0, 1, 2 or 3; Ra, Rb are independently selected from the group consisting of halogen, CN, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C(O)Raa, C(O)NRccRbb and NRccRbb; X is CH2, C(O), S, S(O) or S(O)2; which is located in the 3- or 4-position of the quinoline ring; Ar is a radical Ar1, Ar2-Ar3 or Ar2-O-Ar3, wherein Ar1, Ar2 and Ar3 are each independently selected from the group consisting of aryl or hetaryl wherein aryl or hetaryl moieties may be unsubstituted or may carry 1, 2, 3 substituents Rx, wherein and physiologically tolerated acid addition salts and the N-oxides thereof.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to compounds of formula (I) wherein A is C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C3-C6-cycloalkyl, aryl-C1-C4-alkyl, aryl-C2-C4-alkenyl, aryl or hetaryl; --- is a single or double bond; X1 and X2 are N, CRx1, NRx2 or CRx3Rx4; Rx1, Rx3 and Rx4 are H, halogen, CN, NO2, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylcarbonyl, etc. or two geminal radicals Rx3 and Rx4 together with the carbon atom to which they are bound may form a carbonyl group or a 3- to 6-membered carbocyclic or heterocyclic spiro- annulated ring; Rx2 is hydrogen, C1-C6-alkyl, C1-C6-alkylcarbonyl, C1-C6-haloalkyl, etc.; or two vicinal radicals Rx1, Rx2, Rx3 or Rx4 together with X1 and X2 form a five- or six- membered carbocyclic or heterocyclic fused ring; Y1, Y2 and Y3 are N or CRy; Ry is H, halogen, CN, NO2, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylcarbonyl, C1-C6-haloalkyl, etc.; wherein a maximum of 3 of the radicals X1, X2, Y1, Y2 and Y3 are selected from NRx1 and N; R1 is hydrogen, C1-C6-alkyl, C1-C6-hydroxyalkyl, C1-C6-haloalkyl, etc.; R2 is C1-C4-alkyl or C1-C4-haloalkyl; n is 0, 1 or 2; physiologically tolerated acid addition salts and the N-oxides thereof, pharmaceutical composition comprising them, a method for treating medical disorders selected from diseases of the central nervous system, addiction diseases or obesity, said method comprising administering an effective amount of such compounds to a subject in need and the use of such a compound for preparing a pharmaceutical compositions.

IPC Classes  ?

• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 471/04 - Ortho-condensed systems
• A61K 31/404 - Indoles, e.g. pindolol
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to compounds of the general formula (I) in which A, B, R1, R2 and Het have the meaning given in claim 1; Y is a bivalent group of the formula (II) in which D is C1-C3-alkylene, where D may have a substituent R5; R3 is hydrogen, C1-C8-alkyl or together with R4 is C1-C3-alkylene which may have a radical R5a, or together with R5 is C1-C3-alkylene, and R4 is hydrogen, C1-C8-alkyI or together with R3 is C1-C3-alkylene which may have a radical R5a, or together with R5 is C1-C3-alkylene, where R5 together with R5a, where present, are a bond or C1-C3-alkylene; and where one of the following conditions is satisfied: R3 together with R4 is C1-C3-alkylene which may have a radical R5a; or R3 together with R5 is C1-C3-alkylene; or R4 together with R5 is C1-C3-alkylene where the radical A is different from phenyl when the radical B is phenyl or naphthyl; and medicaments which comprise such compounds and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent and/or oxytocin-dependent diseases.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 471/08 - Bridged systems
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 13/00 - Drugs for disorders of the urinary system
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to a method for the treatment of an amyloidosis such as Alzheimer's disease in a subject in need thereof, characterized in that it comprises administering an inhibitor of the interaction between Aβ globulomer and the P/Q type voltage-gated presynaptic calcium channel to said subject.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to a method for the treatment of an amyloidosis such as Alzheimer's disease in a subject in need thereof, characterized in that it comprises administering an agonist of the P/Q type voltage-gated presynaptic calcium channel to said subject.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/015 - Hydrocarbons carbocyclic
• A61K 31/05 - Phenols
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3a, R3b, W, Y and X have the meanings mentioned in the claims and 15 the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I-A.a' and I-A.a'' in which m, E, R1, R3a, R3b, R2, Ry, Rw and Rw6* have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof.

IPC Classes  ?

• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 493/04 - Ortho-condensed systems
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to novel oxindole derivatives of the formula (I) to medicaments comprising them and to their use for the prophylaxis and/or treatment of diseases vasopressin dependent.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to novel oxindole derivatives of the formula (I) to medicaments comprising them and to their use for the prophylaxis and/or treatment of diseases vasopressin dependent.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to novel oxindole derivatives of the formula (I) to medicaments comprising them and to their use for the prophylaxis and/or treatment of diseases vasopressin dependent.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to novel oxindole derivatives of the general formula (I) to medicaments comprising them and to their use for the prophylaxis and/or treatment of diseases vasopressin dependent.

IPC Classes  ?

• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

IPC Classes  ?

• A61K 8/18 - Cosmetics or similar toiletry preparations characterised by the composition
• A61Q 13/00 - Formulations or additives for perfume preparations
• C12P 21/06 - Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products

Abstract

The subject invention relates to monoclonal antibodies that may be used in the treatment and diagnosis of Alzheimer's Disease. In particular, the present invention relates to monoclonal antibodies referred to as 10F4 and 3C5 and to other monoclonal antibodies (e.g., murine, human or humanized) having similar properties thereto.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• C12N 15/09 - Recombinant DNA-technology

Abstract

The invention relates to a device for forming moulded bodies from a mouldable mass comprising a matrix grid (19) in which at least one receiving chamber (21) is accommodated, and at least one tool (17, 18) with which the mouldable mass can be pressed into the receiving chamber (21). Said claimed device is characterised in that the tool (17, 18) can be displaced along a guide path (3A, 3B) that comprises a moulding section (A), in which a constant pressure is exerted upon portions of the mouldable mass on the strip by the tools (17, 18), said mass being disposed in the receiving chamber (21). The invention further relates to a method for forming moulded bodies, in which a mouldable mass is formed and is guided to at least one receiving chamber of a matrix grid (1). At least one tool (17, 18) then presses one portion of the mouldable mass into the receiving chamber (21), in which the tool (17, 18) is displaced along a guide path (3) that comprises a moulding section (A), wherein a constant pressure is exerted upon the portions of the mouldable mass on the strip by the tools (17, 18), said portions being disposed in the receiving chamber (21).

IPC Classes  ?

• B30B 11/14 - Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses or tabletting presses using a ram exerting pressure on the material in a moulding space co-operating with moulds on a movable carrier other than a turn-table or a rotating drum
• B30B 15/00 - Details of, or accessories for, pressesAuxiliary measures in connection with pressing
• B30B 15/30 - Feeding material to presses
• B30B 15/34 - Heating or cooling presses or parts thereof

Abstract

The invention relates to a device for forming mouldable bodies (57) from a mouldable mass by means of a matrix grid (19), in which at least one cavity (21) is formed by lateral limiting elements (20), and at least one tool (17, 18) which compresses the mouldable mass into the cavity (21). The inventive device is characterised by a compression partition (38) that can be displaced on the matrix grid (19) for portioning the mouldable mass. Said compression partition (38) comprises lateral limiting elements (39) that correspond to the lateral limiting elements (20) of the matrix grid (19). The invention also relates to a method for forming mouldable bodies (57) consisting of forming a mouldable mass and guiding it to a matrix grid (19) such that it rests on the front face (45) of the lateral limiting elements (20) of the matrix grid (19). A compression partition (38) with lateral limiting elements (39), that correspond to the lateral limiting elements (20) of the matrix grid (19), is displaced towards the matrix grid (19) to reduce the part (14A) of the mouldable mass on the lateral limiting elements (20) of the matrix grid (19) in the direction of a cavity (21) formed by the matrix grid (19) between the lateral limiting elements (20), thus portioning the mouldable mass. At least one tool (17, 18) compresses the portions of the mouldable mass in the cavity (21).

IPC Classes  ?

• B30B 15/00 - Details of, or accessories for, pressesAuxiliary measures in connection with pressing
• B30B 15/30 - Feeding material to presses
• B30B 15/34 - Heating or cooling presses or parts thereof

Abstract

Provided are cosmetic preparations for topical application containing nanocrystals of cosmetic actives leading to an increased bioactivity of the molecules in the skin and methods of making the cosmetic preparations. The nanocrystals can be added to any cosmetic topical formulation, e. g. creams, lotions and liposomal dispersions. The drug nanocrystals are produced by a combination process of low energy pearl milling followed by a high energy high-pressure homogenization leading to nanocrystal suspensions (nanosuspensions) of improved physical stability.

IPC Classes  ?

• A61K 8/34 - Alcohols
• A61K 8/04 - DispersionsEmulsions
• A61K 8/49 - Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• A61K 8/60 - SugarsDerivatives thereof
• A61K 8/67 - Vitamins
• A61Q 19/00 - Preparations for care of the skin

Abstract

The invention provides a dosage form, comprising a melt-processed mixture of (a) a pharmaceutically effective amount of imatinib or a salt thereof, (b) at least one polymeric binder, and (c) at least one pharmaceutically acceptable non-ionic surfactant. The invention provides imatinib dosage forms with high drug loading which can be prepared in a simple and efficient manner, imatinib dosage forms from which the active principle is released in an essentially pH-independent fashion, and extended release imatinib dosage forms.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim

Abstract

A pharmaceutical dosage form comprises a solid dispersion product of at least one tyrosine kinase inhibitor, at least one pharmaceutically acceptable polymer, and at least one pharmaceutically acceptable solubilizer.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim

Abstract

The present invention relates to a solid dosage form with at least one film (1), which contains an active substance at least in sections. The dosage form is characterized in that the concentration of active substance in film (1) or in the films has a gradient in a direction normal to the thickness of film (1). The invention further relates to a method of production of a solid dosage form with an active substance, in which at least one film (1) is produced, which contains an active substance at least in sections, with the concentration of active substance in film (1) or in the films having a gradient in the longitudinal direction of the film. This film is then formed to produce the dosage form.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 9/70 - Web, sheet or filament bases

Abstract

The present invention relates to a heterocyclic compound of the general formula (I) and their use and preparation, methods of making the compounds, compositions containing at least one of said compounds, and methods of treatment using at least one compound. In particular, compounds of the general formula (I) are useful for inhibiting glycogen synthase kinase 3 (GSK-3),

IPC Classes  ?

• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 25/00 - Drugs for disorders of the nervous system