EP1551792A1 - Nouveaux betamimetiques a duree d'action prolongee, procedes de production et d'utilisation comme medicaments - Google Patents

Nouveaux betamimetiques a duree d'action prolongee, procedes de production et d'utilisation comme medicaments

Info

Publication number
EP1551792A1
EP1551792A1 EP03750623A EP03750623A EP1551792A1 EP 1551792 A1 EP1551792 A1 EP 1551792A1 EP 03750623 A EP03750623 A EP 03750623A EP 03750623 A EP03750623 A EP 03750623A EP 1551792 A1 EP1551792 A1 EP 1551792A1
Authority
EP
European Patent Office
Prior art keywords
methyl
compounds
alkyl
acid
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03750623A
Other languages
German (de)
English (en)
Inventor
Thierry Bouyssou
Frank Buettner
Ingo Konetzki
Sabine Pestel
Andreas Schnapp
Hermann Schollenberger
Kurt Schromm
Claudia Heine
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Boehringer Ingelheim Pharma GmbH and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim Pharma GmbH and Co KG
Publication of EP1551792A1 publication Critical patent/EP1551792A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
    • C07C217/66—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain
    • C07C217/70—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Definitions

  • the present invention relates to compounds of general formula 1
  • radicals R 1 , R 2 and R 3 can have the meanings given in the claims and in the description, processes for their preparation and their use as medicaments, in particular for the treatment of inflammatory and obstructive respiratory diseases.
  • Betamimetics ( ⁇ -adrenergic substances) are known from the prior art. They can be used in a variety of therapeutic areas.
  • An application once a day has the advantage that the patient is relatively quick can get used to the regular use of the drug at certain times of the day.
  • betamimetics which are characterized by a longer duration of action and can therefore be used for the production of medicaments with a longer activity. It is a particular object of the present invention to provide betamimetics which, owing to their long effectiveness, can be used to produce a medicament which can be applied once a day. Another object of the present invention is to provide new beta mimetics which, owing to their long effectiveness, can be used to produce a medicament which can be applied once a day for the treatment of inflammatory or obstructive respiratory diseases.
  • betamimetics which are not only extremely potent but are also characterized by a high degree of selectivity towards the ⁇ 2 -adreno-receptor.
  • R 1 -C 4 alkyl R 2 QG t alkyl
  • R 3 C 1 -C 4 -alkyl or phenyl, which can optionally be mono- or polysubstituted, or R 2 and R 3 together form a divalent group selected from -CH 2 -CH 2 - and -CH 2 -CH 2 -CH 2 - mean.
  • Compounds of formula 1 are preferred in which R 1 is C 1 -C 4 -alkyl; R 2 CC 4 alkyl;
  • R 3 -C 1 -alkyl or phenyl which may optionally be mono-, di-, tri- or tetrasubstituted by one or more radicals selected from -C 3 -alkyl,
  • CF 3 methoxy, ethoxy, hydroxy, fluorine, chlorine, bromine, -OCF 3 , -CHF 2 , -NHCOCH 3 and -NHSO 2 CH 3 , or R 2 and R 3 together form a divalent group selected from -CH 2 -CH 2 - and -CH 2 -CH 2 -CH 2 - mean.
  • R 1 is C 1 -C 4 -alkyl, preferably methyl;
  • R 3 -C 4 alkyl or phenyl which may optionally be mono-, di-, tri- or tetra-substituted by one or more radicals selected from methyl, ethyl, CF 3 , methoxy, ethoxy and hydroxy, or R 2 and R 3 together represent a double-bonded group selected from -CH 2 -CH 2 - and -CH 2 -CH 2 -CH 2 -.
  • R 1 - alkyl preferably methyl
  • R 2 QQ-alkyl preferably methyl
  • R 3 -C-alkyl preferably methyl, or phenyl, which may optionally be substituted once, twice, three or four times by one or more radicals selected from methyl, CF 3 , methoxy and hydroxy, or R 2 and R. 3 together represent the double-bonded group -CH 2 -CH 2 -.
  • R 1 is methyl or ethyl, preferably methyl; R 2 methyl; R 3 is methyl, ethyl or phenyl, which may optionally be mono-, di-, tri- or tetrasubstituted by one or more radicals selected from methyl, CF 3 , methoxy and hydroxy, or R 2 and R 3 together form the divalent group - CH 2 -CH 2 - mean.
  • R 3 is methyl or phenyl, which may optionally be mono-, di- or trisubstituted by one or more radicals selected from methyl, ethyl and hydroxy, or R 2 and R 3 together denote the -CH -CH 2 - group.
  • R 2 and RR 33 together mean the double-bond group -CH 2 -CH 2 .
  • the invention relates to the respective compounds of formula 1, optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates, in the form of the free bases or the corresponding acid addition salts with pharmacologically acceptable acids.
  • the compounds of general formula 1 according to the invention can optionally be present in the form of their individual optical isomers, mixtures of the individual enantiomers or racemates and can be separated into the pure forms using methods known from the literature. If the compounds are used in enantiomerically pure form, the R enantiomers are preferred.
  • Acid addition salts are understood to mean salts which are formed with pharmacologically acceptable acids selected from the group consisting of hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, methanesulfonic acid, nitric acid, maleic acid, acetic acid, benzoic acid, citric acid, fumaric acid, tartaric acid; Oxalic acid, succinic acid and toluenesulfonic acid, preferably hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, fumaric acid and methanesulfonic acid.
  • pharmacologically acceptable acids selected from the group consisting of hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, methanesulfonic acid, nitric acid, maleic acid, acetic acid, benzoic acid, citric acid, fumaric acid, tartaric acid; Oxalic acid, succinic acid and toluenesulfonic
  • the alkyl groups are branched and unbranched alkyl groups having 1 to 4 carbon atoms. Examples include: methyl, ethyl, propyl or butyl.
  • the abbreviations Me, Et, Pr or Bu may also be used to denote the groups methyl, ethyl, propyl or butyl.
  • the definitions propyl and butyl encompass all conceivable isomeric forms of the respective radicals.
  • propyl includes n-propyl and iso-propyl
  • butyl includes iso-butyl, sec. Butyl and tert-butyl, etc.
  • Hydrochloric acid, methanesulfonic acid, benzoic acid and acetic acid are particularly preferred according to the invention.
  • the compounds according to the invention can be prepared analogously to procedures already known in the prior art. Suitable manufacturing processes are known for example from US 3657244, to which reference is made here in full.
  • 6.5 g of l- (3,4-dihydroxy-2-methoxy-phenyl) -2- (l, l-dimethyl-propylamino) -ethanone are hydrogenated with 0.1 g of platinum oxide as a catalyst in 125 ml of methanol.
  • the catalyst is suctioned off and the solvent is distilled off under reduced pressure.
  • the residue is dissolved in ethyl acetate, the crystals which precipitate are filtered off with suction and washed with ethyl acetate and diethyl ether.
  • 35 g of bromine-2-methoxy-3,4-diphenylmethylene dioxyacetophenone are refluxed with 45 g of 1-methyl-cyclopentylamine in 150 ml of ethanol for 1 hour.
  • the inorganic salts are then filtered off and the solvent is distilled off.
  • the residue is dissolved in ethyl acetate, acidified with ethereal hydrochloric acid and mixed with diethyl ether.
  • the solid which precipitates out is filtered off, washed with diethyl ether and then boiled in water. The product is obtained after filtration and drying.
  • the compounds of general formula 1 are distinguished by a wide range of possible uses in the therapeutic field. To be emphasized are those possible uses for which the compounds of formula 1 according to the invention can preferably be used as beta-mimetics due to their pharmaceutical activity.
  • the compounds of general formula 1 can be used alone or in combination with other active compounds of formula 1 according to the invention. If appropriate, the compounds of the general formula 1 can also be used in combination with other pharmacologically active compounds. These are in particular anticholinergics, antiallergics, PAF antagonists, PDE IV inhibitors, leukotriene antagonists, p38 kinase inhibitors, EGFR kinase inhibitors and corticosteroids, and combinations of active substances thereof.
  • Examples of preferred anticholinergics that can be used in combination with the compounds of formula 1 include compounds selected from the group consisting of tiotropium salts, ipratropium salts, oxitropium salts, salts of the compounds N-methyl-2 known from WO 02/32899 , 2-Diphenylpropionklaretropenolester, N-methyl-2,2-Diphenylpropionsäurescopinester, N-Methyl-2-Fluor-2,2-Diphenylessigklascopinester and N-Methyl-2-fluoro-2,2-Diphenylacetic Acid Tropenolester as well as salts of the from WO 02 / 32899 known compounds N-methyl-3,3 ', 4,4'-tetraf uorbenzilklaretropenolester, N-methyl-3, 3', 4,4'-tetrafluorobenzilklarescopinester;N-methyl-4,4'-dichlorobenzic acid copinate ester,
  • N-ethyl-4,4'-difluorobenzilic acid tropenol esters optionally in the form of their hydrates and solvates.
  • Salts are understood to mean those compounds which, in addition to the cations mentioned above, contain a single negatively charged anion selected from the group consisting of chloride, bromide and methanesulfonate as counterion.
  • the bromides or methanesulfonates of the abovementioned structures are particularly preferred as active ingredients in the context of the present invention.
  • compositions which, in addition to the compounds of formula 1 according to the invention, contain tiotropium bromide as a further active ingredient are particularly preferred according to the invention. This combination is of particular importance in the treatment of asthma or COPD, especially COPD. Of particular importance here are those combinations which contain the tiotropium bromide in the form of its crystalline monohydrate known from WO 02/30928 or in the form of its crystalline anhydride known from WO 03/000265:
  • corticosteroids which can optionally be used in combination with the compounds of formula 1,
  • the corticosteroids are preferably selected from the group consisting of flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide and dexametasone, with here the budesonide, fluticasone, mometasone and ciclesonide, in particular the budesonasone and one Importance.
  • steroids is used in the context of the present patent application instead of the term corticosteroids.
  • a reference to steroids concludes in the context of the present
  • Invention a reference to salts or derivatives that can be formed by the steroids.
  • Examples of possible salts or derivatives are: sodium salts, sulfobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates. If necessary, the corticosteroids can also be present in the form of their hydrates.
  • PDE-IV inhibitors which can be used according to the invention as a combination with the compound of formula 1
  • compounds which are selected from the group consisting of Enprofylline, Roflumilast, Ariflo, Bay-198004, CP-325,366, BY343, D-4396 (Sch-351591), V-11294A, Z-15370 and AWD-12-281.
  • Preferred PDE-IV inhibitors are selected from the group consisting of Enprofylline, Roflumilast, Ariflo, Z15370 and AWD-12- 281, with AWD-12-281 being particularly preferred as a combination partner with the compound of the formula I_ according to the invention.
  • a reference to the aforementioned PDE-IV inhibitors includes a reference to the present invention optionally existing pharmacologically acceptable acid addition salts.
  • the physiologically tolerable acid addition salts which can be formed by the abovementioned PDE-IV inhibitors are understood as pharmaceutically tolerable salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, JM-lactic acid , Citric acid, tartaric acid or maleic acid.
  • the salts selected from the group consisting of acetate, hydrochloride, hydrobromide, sulfate, phosphate and methanesulfonate are preferred in this context.
  • dopamine agonists which can optionally be used in combination with the compounds of formula 1, are understood to mean compounds which are selected from the group consisting of bromocriptine, cabergoline, alpha-dihydroergocryptine, lisuride, pergolide, pramipexole , Roxindol, Ropinirol, Talipexol, Tergurid and Viozan.
  • dopamine agonists preference is given to using dopamine agonists as combination partners with the compounds of the formula 1 which are selected from the group consisting of pramipexole, talipexole and viozan, pramipexole being of particular importance.
  • a reference to the above-mentioned dopamine agonists includes a reference to their optionally existing pharmacologically acceptable acid addition salts and, if appropriate, their hydrates.
  • the physiologically tolerable acid addition salts which can be formed by the above-mentioned dopamine agonists are understood to mean, for example, pharmaceutically tolerable salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid and are maleic acid.
  • antiallergics which can be used according to the invention as a combination with the compounds of formula 1 are epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, mizolastine, ketotifen, emedastine, dimetindene, clemastine, bamipine, cexchlorpheniramine, pheniramine, Doxylamine, chlorphenoxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and meclozin.
  • Preferred antiallergics which are used in the context of the present invention in combination with the compounds of the formula 1 according to the invention are selected from the group consisting of epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, ebastine, desloratidine and mizolastine, with epinastine and desloratidine being particularly preferred.
  • a reference to the abovementioned antiallergics includes a reference to their pharmacologically acceptable acid addition salts which may exist.
  • 4 - [(3-chloro-4-fluorophenyl) amino] -7- [4 may be mentioned as a particularly preferred example of EGFR kinase inhibitors which can be used in combination with the compounds of the formula 1 according to the invention - ((R) -6-methyl-2-oxo-morpholin-4-yl) - butyloxy] -6 - [(vinylcarbonyl) amino] -quinazoline; 4 - [(3-Chloro-4-fluorophenyl) amino] -7- [4- ((S) -6-methyl-2-oxo-morpholin-4-yl) butyloxy] -6 - [(vinylcarbonyl ) amino] -quinazoline, 4- [(3-chloro-4-fluoro-phenyl) amino] -7- (2- ⁇ 4 - [(S) - (2-oxo-tetrahydrofuran-5-yl) carbonyl] - piperazin
  • the EGFR kinase inhibitors are understood according to the invention to be pharmaceutically acceptable salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or Are maleic acid.
  • the salts of the EGFR kinase inhibitors are preferably selected from the salts of acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and methanesulfonic acid.
  • p38 kinase inhibitors which can be used in combination with the compounds of formula 1 according to the invention, l- [5-tert-butyl-2-> -tolyl-2H-pyrazole-3- yl] -3- [4- (2-morpholin-4-yl-ethoxy) naphthalen-1-yl] urea; 1 - [5-tert-Butyl-2 - /?
  • a reference to the above-mentioned p38 kinase inhibitors in the context of the present invention includes a reference to their pharmacologically acceptable acid addition salts which may exist.
  • the physiologically or pharmacologically acceptable acid addition salts which can be formed by the p38 kinase inhibitors are understood to be pharmaceutically acceptable salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, J are lactic acid, citric acid, tartaric acid or maleic acid.
  • the combination of steroids, PDE IV inhibitors or anticholinergics is particularly preferred from the compound classes mentioned above.
  • the combination with anticholinergics is of particular importance.
  • Suitable forms of application for the application of the compounds of formula 1 are, for example, tablets, capsules, suppositories, solutions etc. According to the invention is of particular importance (in particular in the treatment of
  • the proportion of the pharmaceutically active compound (s) should each be in the range of
  • Corresponding tablets can be mixed, for example, by mixing the active ingredient (s) with known auxiliaries, for example inert diluents, such as Calcium carbonate, calcium phosphate or milk sugar, disintegrants, such as corn starch or alginic acid, binders, such as starch or gelatin, lubricants, such as magnesium stearate or talc, and / or agents for achieving the depot effect, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate.
  • auxiliaries for example inert diluents, such as Calcium carbonate, calcium phosphate or milk sugar, disintegrants, such as corn starch or alginic acid, binders, such as starch or gelatin, lubricants, such as magnesium stearate or talc, and / or agents for achieving the depot effect, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate.
  • the tablets can also
  • coated tablets can be produced by coating cores produced analogously to the tablets with agents conventionally used in tablet coatings, for example collidone or shellac, gum arabic, talc, titanium dioxide or sugar.
  • the core can also consist of several layers to achieve a deposit effect or to avoid incompatibilities.
  • the coated tablet shell can also consist of several layers in order to achieve a depot effect, it being possible to use the auxiliaries mentioned above for the tablets.
  • Juices of the active substances or combinations of active substances according to the invention can additionally contain a sweetener such as saccharin, cyclamate, glycerol or sugar as well as a taste-improving agent, e.g. Flavorings, such as vanillin or orange extract, contain. They can also contain suspending agents or thickening agents, such as sodium carboxymethyl cellulose, wetting agents, for example condensation products of fatty alcohols with ethylene oxide, or protective agents, such as p-hydroxybenzoates.
  • Solutions are usually, e.g. with the addition of isotonants, preservatives, such as p-hydroxybenzoates, or stabilizers, such as alkali metal salts of ethylenediaminetetraacetic acid, optionally using emulsifiers and / or dispersants, where, for example, when using water as a diluent, organic solvents can optionally be used as solubilizers or auxiliary solvents , manufactured and filled into injection bottles or ampoules or infusion bottles.
  • preservatives such as p-hydroxybenzoates
  • stabilizers such as alkali metal salts of ethylenediaminetetraacetic acid
  • emulsifiers and / or dispersants where, for example, when using water as a diluent, organic solvents can optionally be used as solubilizers or auxiliary solvents , manufactured and filled into injection bottles or ampoules or infusion bottles.
  • the capsules containing one or more active ingredients or combinations of active ingredients can be produced, for example, by mixing the active ingredients with inert carriers, such as milk sugar or sorbitol, and encapsulating them in gelatin capsules.
  • Suitable suppositories can be produced, for example, by mixing them with carrier agents such as neutral fats or polyethylene glycol or its derivatives.
  • auxiliaries are water, pharmaceutically acceptable organic solvents, such as paraffins (for example petroleum fractions), oils of vegetable origin (for example peanut or sesame oil), monofunctional or polyfunctional alcohols (for example ethanol or glycerol), carriers such as natural rock meal (for example kaolins, clays, Talc, chalk) synthetic rock flour (e.g.
  • silica and silicates highly disperse silica and silicates
  • sugar e.g. cane, milk and dextrose
  • emulsifiers e.g. lignin, sufite liquor, methylcellulose, starch and polyvinylpyrrolidone
  • lubricants e.g. magnesium stearate, talc, stearic acid and sodium lauryl
  • the tablets can of course also contain additives, such as e.g. Contain sodium citrate, calcium carbonate and dicalcium phosphate together with various additives such as starch, preferably potato starch, gelatin and the like.
  • Lubricants such as magnesium stearate, sodium lauryl sulfate and talc can also be used for tableting.
  • the active ingredients can be mixed with various flavor enhancers or colorants.
  • Inhalable dosage forms are inhalable powders, metered-dose aerosols containing propellant gas, or propellant-free inhalation solutions.
  • propellant-free inhalation solutions also includes concentrates or sterile, ready-to-use inhalation solutions.
  • Inhalable powders which can be used according to the invention can contain 1 either alone or in a mixture with suitable physiologically acceptable auxiliaries.
  • the active ingredients 1 are contained in a mixture with physiologically acceptable auxiliaries
  • the following physiologically acceptable auxiliaries can be used to prepare these inhalable powders according to the invention: monosaccharides (e.g. glucose or arabinose), disaccharides (e.g. lactose, sucrose, maltose), oligo- and polysaccharides ( e.g. dextrans), polyalcohols (e.g. sorbitol, mannitol, Xylitol), salts (eg sodium chloride, calcium carbonate) or mixtures of these auxiliaries with one another.
  • monosaccharides e.g. glucose or arabinose
  • disaccharides e.g. lactose, sucrose, maltose
  • oligo- and polysaccharides e.g. dextrans
  • polyalcohols e.g. sorbitol, mannitol, Xylitol
  • salts eg sodium chlor
  • Mono- or disaccharides are preferably used, the use of lactose or glucose being preferred, in particular, but not exclusively, in the form of their hydrates.
  • Lactose most preferably lactose monohydrate, is used as an auxiliary as particularly preferred in the sense of the invention.
  • the auxiliaries have a maximum average particle size of up to 250 ⁇ m, preferably between 10 and 150 ⁇ m, particularly preferably between 15 and 80 / xm. If appropriate, it may seem sensible to add finer excipient fractions with an average particle size of 1 to 9 ⁇ m to the excipients mentioned above. The latter finer excipients are also selected from the group of excipients that can be used.
  • micronized active ingredient 1 preferably with an average particle size of 0.5 to 10 ⁇ m, particularly preferably from 1 to 5 ⁇ m, is admixed with the excipient mixture.
  • Processes for producing the inhalable powders according to the invention by grinding and micronizing and by finally mixing the constituents are known from the prior art.
  • the inhalable powders according to the invention can be applied using inhalers known from the prior art.
  • Inhalation aerosols containing propellant gas according to the invention may contain 1 dissolved in the propellant gas or in dispersed form.
  • 1 can be contained in separate dosage forms or in a common dosage form, where 1 can either be both dissolved, both dispersed or in each case only one component dissolved and the other dispersed.
  • the propellant gases which can be used to produce the inhalation aerosols are known from the prior art. Suitable propellants are selected from the group consisting of hydrocarbons such as n-propane, n-butane or isobutane and halogenated hydrocarbons such as fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane.
  • the above-mentioned propellant gases can be used alone or in mixtures thereof.
  • Particularly preferred propellants are halogenated alkane derivatives selected from TG134a and TG227 and mixtures thereof.
  • the inhalation aerosols containing blowing gases can furthermore contain further constituents such as cosolvents, stabilizers, surfactants, antioxidants, Contains lubricants and agents for adjusting the pH. All of these components are known in the art.
  • the active compounds 1 according to the invention can be applied in the form of propellant-free inhalation solutions and inhalation suspensions.
  • Suitable solvents for this purpose are aqueous or alcoholic, preferably ethanolic, solutions.
  • the solvent can only be water or it is a mixture of water and ethanol.
  • the relative proportion of ethanol to water is not limited, but the maximum limit is preferably up to 70 percent by volume, in particular up to 60 percent by volume and particularly preferably up to 30 percent by volume.
  • the remaining volume percentages are filled up with water.
  • the solutions or suspensions containing 1 are adjusted to a pH of 2 to 7, preferably 2 to 5, using suitable acids. Acids selected from inorganic or organic acids can be used to adjust this pH.
  • Examples of particularly suitable inorganic acids are hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid and / or phosphoric acid.
  • Examples of particularly suitable organic acids are: ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and / or propionic acid and others.
  • Preferred inorganic acids are hydrochloric acid, sulfuric acid. It is also possible to use the acids which already form an acid addition salt with one of the active ingredients. Ascorbic acid, fumaric acid and citric acid are preferred among the organic acids.
  • mixtures of the acids mentioned can also be used, in particular in cases of acids which, in addition to their acidifying properties, also have other properties, e.g. as flavors, antioxidants or complexing agents, such as citric acid or ascorbic acid.
  • hydrochloric acid is particularly preferably used to adjust the pH.
  • the addition of editic acid (EDTA) or one of the known salts thereof, sodium edetate, as a stabilizer or complexing agent may optionally be dispensed with.
  • Other embodiments include this connection (s).
  • the content, based on sodium edetate is particularly below 100 mg / 100 ml, preferably below 50 mg / 100 ml preferably below 20 mg / 100ml. Inhalation solutions in which the sodium edetate content is 0 to 10 mg / 100 ml are generally preferred.
  • Co-solvents and / or other auxiliaries can be added to the propellant-free inhalation solutions.
  • Preferred co-solvents are those which contain hydroxyl groups or other polar groups, for example alcohols - in particular isopropyl alcohol, glycols - in particular propylene glycol, polyethylene glycol, polypropylene glycol, glycol ether, glycerol, polyoxyethylene alcohols and polyoxyethylene fatty acid esters.
  • additives and additives are understood to mean any pharmacologically acceptable substance which is not an active substance, but which can be formulated together with the active substance (s) in the pharmacologically suitable solvent in order to improve the qualitative properties of the active substance formulation.
  • the JJffilfs and additives include e.g. surfactants such as Soy lecithin, oleic acid, sorbitan esters, such as polysorbates, polyvinylpyrrolidone, other stabilizers, complexing agents, antioxidants and / or preservatives which ensure or extend the useful life of the finished pharmaceutical formulation, flavors, vitamins and / or other additives known in the prior art.
  • the additives also include pharmacologically acceptable salts such as sodium chloride as isotonic agents.
  • the preferred auxiliary substances include antioxidants, such as, for example, ascorbic acid, unless already used for adjusting the pH, vitamin A, vitamin E, tocopherols and similar vitamins or provitamins occurring in the human organism.
  • Preservatives can be used to protect the formulation from contamination with germs. Suitable preservatives are those known from the prior art, in particular cetylpyridinium chloride, benzalkonium chloride or benzoic acid or benzoates such as sodium benzoate in the concentration known from the prior art.
  • the preservatives mentioned above are preferably present in concentrations of up to 50 mg / 100 ml, particularly preferably between 5 and 20 mg / 100 ml.
  • preferred formulations only contain benzalkonium chloride and sodium edetate. In another preferred embodiment, sodium edetate is dispensed with.
  • the dosage of the compounds according to the invention is of course strongly dependent on the type of application and the disease to be treated.
  • the compounds of formula 1 are highly effective even at doses in the ⁇ g range. Even above the ⁇ g range, the compounds of formula 1 can be used expediently.
  • the dosage can then be in the gram range, for example.
  • the compounds according to the invention can be administered with a higher dosage (for example, but not in a limiting manner in the range from 1 to 1000 mg).
  • the finely ground active ingredient, milk sugar and part of the corn starch are mixed together.
  • the mixture is sieved, whereupon it is moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet-granulated and dried.
  • the granules, the rest of the corn starch and the magnesium stearate are sieved and mixed together.
  • the mixture is compressed into tablets of a suitable shape and size.
  • the finely ground active ingredient, part of the corn starch, milk sugar, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is sieved and processed with the rest of the corn starch and water to form a granulate which is dried and sieved.
  • the sodium carboxymethyl starch and the magnesium stearate are added, the mixture is mixed and compressed into tablets of a suitable size.
  • the active ingredient is dissolved in water at its own pH or, if appropriate, at pH 5.5 to 6.5, and sodium chloride is added as an isotonic agent.
  • the solution obtained is filtered pyrogen-free and the filtrate is filled into ampoules under aseptic conditions, which are then sterilized and melted.
  • the ampoules contain 5 mg, 25 mg and 50 mg of active ingredient.
  • the suspension is filled into a conventional aerosol container with a metering valve. 50 ⁇ l of suspension are preferably dispensed per actuation. If desired, the active ingredient can also be dosed at a higher level (e.g. 0.02% by weight).
  • This solution can be prepared in the usual way.
  • the inhalable powder is produced in the usual way by mixing the individual components.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Endocrinology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des composés de formule générale (1), dans laquelle les restes R<1>, R<2> et R<3> peuvent avoir les significations mentionnées dans les revendications et la description. Cette invention concerne également des procédés de production et d'utilisation desdits composés comme médicaments, notamment dans le traitement de maladies respiratoires inflammatoires et obstructives.
EP03750623A 2002-10-04 2003-09-25 Nouveaux betamimetiques a duree d'action prolongee, procedes de production et d'utilisation comme medicaments Withdrawn EP1551792A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10246374 2002-10-04
DE10246374A DE10246374A1 (de) 2002-10-04 2002-10-04 Neue Betamimetika mit verlängerter Wirkungsdauer, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
PCT/EP2003/010661 WO2004033412A1 (fr) 2002-10-04 2003-09-25 Nouveaux betamimetiques a duree d'action prolongee, procedes de production et d'utilisation comme medicaments

Publications (1)

Publication Number Publication Date
EP1551792A1 true EP1551792A1 (fr) 2005-07-13

Family

ID=32010227

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03750623A Withdrawn EP1551792A1 (fr) 2002-10-04 2003-09-25 Nouveaux betamimetiques a duree d'action prolongee, procedes de production et d'utilisation comme medicaments

Country Status (6)

Country Link
EP (1) EP1551792A1 (fr)
JP (1) JP2006502207A (fr)
AU (1) AU2003270262A1 (fr)
CA (1) CA2501055A1 (fr)
DE (1) DE10246374A1 (fr)
WO (1) WO2004033412A1 (fr)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7056916B2 (en) 2002-11-15 2006-06-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
GB0401334D0 (en) 2004-01-21 2004-02-25 Novartis Ag Organic compounds
ATE539754T1 (de) * 2004-04-22 2012-01-15 Boehringer Ingelheim Int Arzneinmittelkombinationen enthaltend benzoxazine zur behandlung von atemwegserkrankungen
US7220742B2 (en) 2004-05-14 2007-05-22 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments
GB0411056D0 (en) 2004-05-18 2004-06-23 Novartis Ag Organic compounds
GT200500281A (es) 2004-10-22 2006-04-24 Novartis Ag Compuestos organicos.
GB0424284D0 (en) 2004-11-02 2004-12-01 Novartis Ag Organic compounds
GB0426164D0 (en) 2004-11-29 2004-12-29 Novartis Ag Organic compounds
GB0507577D0 (en) 2005-04-14 2005-05-18 Novartis Ag Organic compounds
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
DE102005030733A1 (de) * 2005-07-01 2007-01-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittelkombinationen zur Behandlung von Atemwegserkrankungen enthaltend langwirksame Beta-2-Agonisten und wenigstens einen weiteren Wirkstoff
GB0516313D0 (en) 2005-08-08 2005-09-14 Argenta Discovery Ltd Azole derivatives and their uses
JP2009504602A (ja) * 2005-08-08 2009-02-05 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング チオトロピウム塩類を投与することを含む心疾患のリスクに対する保護の方法
EP1924553A1 (fr) 2005-08-08 2008-05-28 Argenta Discovery Limited Dérivés bicyclo[2.2.]hept-7-ylamine et leurs utilisations
ES2530991T3 (es) 2005-08-15 2015-03-09 Boehringer Ingelheim Int Procedimiento para la obtención de betamiméticos
EP2532677A1 (fr) 2005-10-21 2012-12-12 Novartis AG Anticorps humains dirigés contre l'IL -13 et utilisations thérapeutiques
GB0601951D0 (en) 2006-01-31 2006-03-15 Novartis Ag Organic compounds
PL2322525T3 (pl) 2006-04-21 2014-03-31 Novartis Ag Pochodne puryny do zastosowania jako agoniści receptora adenozyny A<sub>2A</sub>
BRPI0717564A2 (pt) 2006-09-29 2013-10-22 Novartis Ag Pirazolopirimidinas como inibidores de pi3k lipídeo cinase
RS51644B (en) 2007-01-10 2011-10-31 Irm Llc. UNITS AND PREPARATIONS AS CHANNEL INHIBITORS ACTIVATING PROSTHESES
MX2009008493A (es) 2007-02-09 2009-08-20 Irm Llc Compuestos y composiciones como inhibidores de la proteasa activadora de canal.
PL2155721T3 (pl) 2007-05-07 2011-07-29 Novartis Ag Związki organiczne
PT2444120T (pt) 2007-12-10 2018-01-03 Novartis Ag Análogos da amilorida espirocíclicos como bloqueadores de enac
KR20100113557A (ko) 2008-01-11 2010-10-21 노파르티스 아게 키나제 억제제로서의 피리미딘
AU2009256645A1 (en) 2008-06-10 2009-12-17 Novartis Ag Pyrazine derivatives as epithelial sodium channel blockers
US8236786B2 (en) 2008-08-07 2012-08-07 Pulmagen Therapeutics (Inflammation) Limited Respiratory disease treatment
PT2379507E (pt) 2008-12-30 2014-01-21 Pulmagen Therapeutics Inflammation Ltd Compostos de sulfonamida para o tratamento de desordens respiratórias
ES2396023T3 (es) 2009-01-29 2013-02-18 Novartis Ag Bencimidazoles sustituidos para el tratamiento de astrocitomas
WO2010150014A1 (fr) 2009-06-24 2010-12-29 Pulmagen Therapeutics (Inflammation) Limited Glitazones 5r-5–deutérés pour le traitement de maladies respiratoires
US8389526B2 (en) 2009-08-07 2013-03-05 Novartis Ag 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
JP5781510B2 (ja) 2009-08-12 2015-09-24 ノバルティス アーゲー ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用
JP5819831B2 (ja) 2009-08-17 2015-11-24 インテリカイン， エルエルシー 複素環式化合物およびそれらの使用
WO2011020861A1 (fr) 2009-08-20 2011-02-24 Novartis Ag Composés d'oximes hétérocycliques
EP2813227A1 (fr) 2009-10-22 2014-12-17 Vertex Pharmaceuticals Incorporated Compositions pour le traitement de la mucoviscidose et d'autres maladies chroniques
GB0918922D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Aminopyridine derivatives
GB0918924D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Azaindole derivatives
GB0918923D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Aminothiazole derivatives
WO2011098746A1 (fr) 2010-02-09 2011-08-18 Pulmagen Therapeutics (Inflammation) Limited Sels d'addition acide cristallins de l'énantiomère (5r) de la pioglitazone
GB201002224D0 (en) 2010-02-10 2010-03-31 Argenta Therapeutics Ltd Respiratory disease treatment
GB201002243D0 (en) 2010-02-10 2010-03-31 Argenta Therapeutics Ltd Respiratory disease treatment
US8247436B2 (en) 2010-03-19 2012-08-21 Novartis Ag Pyridine and pyrazine derivative for the treatment of CF
WO2012034095A1 (fr) 2010-09-09 2012-03-15 Irm Llc Composés et compositions comme inhibiteurs de trk
US8637516B2 (en) 2010-09-09 2014-01-28 Irm Llc Compounds and compositions as TRK inhibitors
US8372845B2 (en) 2010-09-17 2013-02-12 Novartis Ag Pyrazine derivatives as enac blockers
JP2014505088A (ja) 2011-02-10 2014-02-27 ノバルティス アーゲー Ｃ−ＭＥＴチロシンキナーゼ阻害剤としての［１，２，４］トリアゾロ［４，３−ｂ］ピリダジン化合物
WO2012116237A2 (fr) 2011-02-23 2012-08-30 Intellikine, Llc Composés hétérocycliques et leurs utilisations
US9102671B2 (en) 2011-02-25 2015-08-11 Novartis Ag Compounds and compositions as TRK inhibitors
US8883819B2 (en) 2011-09-01 2014-11-11 Irm Llc Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension
JP5957526B2 (ja) 2011-09-15 2016-07-27 ノバルティス アーゲー チロシンキナーゼとしての６−置換３−（キノリン−６−イルチオ）−［１，２，４］トリアゾロ［４，３−ａ］ピラジン
ES2558457T3 (es) 2011-09-16 2016-02-04 Novartis Ag Compuestos heterocíclicos para el tratamiento de fibrosis quística
WO2013038373A1 (fr) 2011-09-16 2013-03-21 Novartis Ag Dérivés pyrimidinamides
WO2013038378A1 (fr) 2011-09-16 2013-03-21 Novartis Ag Dérivés pyridinamides
WO2013038381A1 (fr) 2011-09-16 2013-03-21 Novartis Ag Dérivés d'amide pyridine/pyrazine
EP2755652B1 (fr) 2011-09-16 2021-06-02 Novartis AG Hétérocyclyle carboxamides n-substitués
EP2793893A4 (fr) 2011-11-23 2015-07-08 Intellikine Llc Régimes de traitement améliorés utilisant des inhibiteurs de mtor
US8809340B2 (en) 2012-03-19 2014-08-19 Novartis Ag Crystalline form
EP3964513A1 (fr) 2012-04-03 2022-03-09 Novartis AG Produits combinés comprenant des inhibiteurs de tyrosine kinase et leur utilisation
US9073921B2 (en) 2013-03-01 2015-07-07 Novartis Ag Salt forms of bicyclic heterocyclic derivatives
CN105246482A (zh) 2013-03-15 2016-01-13 因特利凯有限责任公司 激酶抑制剂的组合及其用途
TW201605450A (zh) 2013-12-03 2016-02-16 諾華公司 Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途
CN106458979B (zh) 2014-04-24 2020-03-27 诺华股份有限公司 作为磷脂酰肌醇3-激酶抑制剂的氨基吡嗪衍生物
KR20160141856A (ko) 2014-04-24 2016-12-09 노파르티스 아게 포스파티딜이노시톨 3-키나제 억제제로서의 피라진 유도체
PT3134396T (pt) 2014-04-24 2019-12-16 Novartis Ag Derivados de amino piridina como inibidores da fosfatidilinositol 3-quinase
WO2016011658A1 (fr) 2014-07-25 2016-01-28 Novartis Ag Polythérapie
US10195208B2 (en) 2014-07-31 2019-02-05 Novartis Ag Combination therapy
WO2020250116A1 (fr) 2019-06-10 2020-12-17 Novartis Ag Dérivé de pyridine et de pyrazine pour le traitement de la fk, de la bpco et de la bronchiectasie
JOP20220044A1 (ar) 2019-08-28 2023-01-30 Novartis Ag مشتقات 1، 3- فينيل أريل غير متجانسة بها استبدال واستخدامها في معالجة مرض

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1543372A1 (de) * 1966-10-18 1971-04-01 Boehringer Sohn Ingelheim Verfahren zur Herstellung von o-substituierten 3,4-Dioxyphenylalkanolaminen
DE3743265A1 (de) * 1987-12-19 1989-06-29 Boehringer Ingelheim Kg Neue ammoniumverbindungen, ihre herstellung und verwendung
IL152140A0 (en) * 2000-04-27 2003-05-29 Boehringer Ingelheim Pharma Novel, slow-acting betamimetics, a method for their production and their use as medicaments

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004033412A1 *

Also Published As

Publication number Publication date
JP2006502207A (ja) 2006-01-19
DE10246374A1 (de) 2004-04-15
AU2003270262A1 (en) 2004-05-04
CA2501055A1 (fr) 2004-04-22
WO2004033412A1 (fr) 2004-04-22

Similar Documents

Publication Publication Date Title
EP1551792A1 (fr) Nouveaux betamimetiques a duree d&#39;action prolongee, procedes de production et d&#39;utilisation comme medicaments
EP1562892A1 (fr) Nouveaux derives de dihydroxymethylphenyle, procedes pour leur preparation, et utilisation desdits derives comme medicament
EP1720546B1 (fr) Nouveaux beta-2-agonistes a action longue duree et leur utilisation comme medicaments
EP1562603B1 (fr) Nouveaux medicaments destines au traitement de la bronchopneumopathie chronique obstructive
EP1911749B1 (fr) Nouveaux agoniste béta-2 à action prolongée et leur utilisation en tant que médicament
EP1328524B1 (fr) Nouveaux anticholinergiques, leurs procedes de production et leur utilisation en tant que medicaments
EP1472251B1 (fr) Nouveaux esters d&#39;acide carboxylique de fluorene, procede permettant de les produire et leur utilisation comme medicaments
EP1472250B1 (fr) Substances anticholinergiques, procédé de préparation associé et utilisation comme médicament
EP1472249B1 (fr) Esters d&#39;acide xanthenecarboxylique de tropenol et de scopine servant d&#39;antagonistes m3, procedes pour les produire et leur utilisation en tant que medicaments
EP1761509A2 (fr) Dérivés de cycloalkyle pour le traitement des maladies respiratoires
WO2001083462A1 (fr) Nouveaux beta-mimetiques a action lente, leurs procedes de production et leur utilisation comme medicament
DE102004001413A1 (de) 3-Hydroxymethyl-4-Hydroxy-Phenyl-Derivate zur Behandlung von chronisch obstruktiver Lungenerkrankung
US20050234134A1 (en) Betamimetics with a prolonged duration of activity, processes for preparing them, and their use as pharmaceutical compositions
DE10258695A1 (de) Neuer, langwirksamer Beta-agonist, Verfahren zu dessen Herstellung und dessen Verwendung als Arzneimittel
EP1497288B1 (fr) Nouveaux esters d&#39;heterocycles d&#39;azote substitues par un hydroxy utilises comme antagonistes du recepteur m3 muscarinique, leur procede de production et leur utilisation comme medicaments
DE10316660A1 (de) Neue Carbonsäureester mit anticholinerger Wirksamkeit, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
EP1487831B1 (fr) Esters de tropenol d&#39;acide difurylglycolique utilises comme anticholinergiques
WO2003024440A1 (fr) Sels d&#39;acide salicylique, procedes de production et d&#39;utilisation desdits sels en tant que medicaments
EP1483231A1 (fr) Nouveaux sels d&#39;acide cinnamique, procedes de production et d&#39;utilisation comme medicaments
DE10216125A1 (de) Salicylsäuresalze, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
DE10216124A1 (de) Neue Zimtsäuresalze, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
DE10051318A1 (de) Neu, langwirksame Betamimetika, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20050504

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK

RIN1 Information on inventor provided before grant (corrected)

Inventor name: HEINE, CLAUDIA

Inventor name: SCHROMM, KURT

Inventor name: SCHOLLENBERGER, HERMANN

Inventor name: SCHNAPP, ANDREAS

Inventor name: PESTEL, SABINE

Inventor name: KONETZKI, INGO

Inventor name: BUETTNER, FRANK

Inventor name: BOUYSSOU, THIERRY

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20060808