[go: up one dir, main page]

WO2004089950A1 - Composes heteroaromatiques tricycliques - Google Patents

Composes heteroaromatiques tricycliques Download PDF

Info

Publication number
WO2004089950A1
WO2004089950A1 PCT/EP2004/003626 EP2004003626W WO2004089950A1 WO 2004089950 A1 WO2004089950 A1 WO 2004089950A1 EP 2004003626 W EP2004003626 W EP 2004003626W WO 2004089950 A1 WO2004089950 A1 WO 2004089950A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
quinoline
alkyl
compound
radical
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.)
Ceased
Application number
PCT/EP2004/003626
Other languages
German (de)
English (en)
Inventor
Norbert Hauel
Henning Draheim
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 International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
Boehringer Ingelheim Pharmaceuticals Inc
Original Assignee
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
Boehringer Ingelheim Pharmaceuticals Inc
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 International GmbH, Boehringer Ingelheim Pharma GmbH and Co KG, Boehringer Ingelheim Pharmaceuticals Inc filed Critical Boehringer Ingelheim International GmbH
Publication of WO2004089950A1 publication Critical patent/WO2004089950A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Definitions

  • the invention relates to tricyclic heteroaromatic compounds and their salts, their preparation and their use as medicaments, in particular as painkillers.
  • Acute pain i.e. short-term, temporary pain
  • pain usually subsides quickly after the causes have been eliminated and, if need be, cause negligible damage to tissues.
  • pain can also last for a long time.
  • chronic pain which is usually associated with tissue damage, inflammation or other ailments.
  • Diseases that are accompanied by chronic or chronic recurring pain include migraines, neuralgia, muscle pain and inflammation pain.
  • Chronic neuronal pain includes postoperative pain, shingles, phantom pain, diabetic neuropathy, pain after chronic nerve compression, and AIDS and cancer in the final stages.
  • first pain also called light pain
  • second pain the so-called dark or dull pain
  • the first pain is encountered as immediate pain with injuries. It is sent to the brain at high speed (about 20 meters per second). If there is no first pain in injuries, the second pain is observed. It reaches the brain much more slowly (about two meters per second), but is more stable and remains as a dull pain over a long period of time.
  • Active substances such as acetylsalicylic acid, paracetamol or ibuprofen are available for the treatment of mild pain or headache. Particularly severe pain is treated with opium-related agents such as codeine, morphine or similar substances. Its main task is to improve the patient's quality of life by suppressing the pain. Opiates and opioids mainly work in the central nervous system. In addition to their pain-relieving effects, they can also sedate (calm), have a euphoric effect, inhibit the respiratory center and dampen the cough. They include substances such as codeine, morphine, tilidine and tramadol.
  • Non-opioid pain relievers usually work in the peripheral nervous system and are also antipyretic and anti-inflammatory.
  • An active ingredient such as caffeine is often added to the active ingredients.
  • Examples of such pain relievers are Double-Gap, Eudorlin, Migraine, Neuralgin, Thomapyrin, Titralgan, and Vivimed.
  • N-type Caicium channel antagonists for the treatment and prevention of pain are described in international applications WO 02/36567, WO 02/36568 and WO 02/36569.
  • the present invention provides new compounds and their salts which are useful for relieving pain, particularly chronic pain. These compounds are described by the general formula (I):
  • X is a nitrogen atom (N), oxygen atom (O) or sulfur atom (S);
  • Y is a nitrogen atom when X represents an oxygen atom or a sulfur atom
  • Y is a nitrogen atom with a bonded radical R 3 or a sulfur atom or an oxygen atom when X represents a nitrogen atom;
  • A is an unsubstituted or substituted mono-, di- or tricyclic aromatic radical which has either no or 1-3 heteroatoms selected from the group Group contains nitrogen, oxygen and sulfur, at least one of the
  • Heteroatoms is a nitrogen atom;
  • R 1 is hydroxy, fluorine, chlorine or bromine, amino, (C ⁇ - 6 ) alkylamino, di (C ⁇ -6 ) alkylamino,
  • R 2 and R 3 independently of one another are hydrogen (H), (C 1-8 ) alkyl or (C 3 -7) cycloalkyl;
  • alkyl describes both saturated and mono- or polyunsaturated aliphatic hydrocarbon radicals.
  • (C n -m) alkyl groups are understood to mean those which contain n to m carbon atoms, n and m being integers.
  • saturated radicals are preferably (C 1 -C 0 ) alkyl groups
  • unsaturated radicals are preferably (C 2 -i 2 ) alkyl groups.
  • alkyl encompasses both straight-chain and branched hydrocarbon radicals.
  • straight-chain radicals are preferably (C ⁇ -8 ) alkyl groups
  • branched radicals are preferably (C 3 - ⁇ o) alkyl groups.
  • Hydrogen atoms of alkyl radicals can be partially or completely replaced by halogen atoms.
  • halogen atoms are the atoms of fluorine, chlorine, bromine and iodine. If all hydrogen atoms are replaced by halogens, the term "perhalogen alkyl" radical is also used.
  • cycloalkyl is used to summarize saturated and mono- or polyunsaturated aliphatic hydrocarbon radicals which form cyclic, ie ring-shaped closed carbon chains which do not represent an aromatic ring system.
  • Cycloalkyl groups (C n -m) are those whose ring structure is composed of n until m carbon atoms are formed, where n and m are integers which are greater than 2. Unless otherwise defined, they are preferably monocyclic (C 3 -s) cycloalkyl groups.
  • heterocycloalkyl describes cycloalkyl radicals whose closed chain contains one or more heteroatoms in addition to carbon atoms. These heteroatoms can be nitrogen, oxygen or sulfur atoms.
  • the (Cn-m) heterocycloalkyl groups are those whose ring structure is formed from n to m atoms , where n and m are integers greater than 3. Unless otherwise defined, monocyclic (C. 8 ) and bicyclic (C 8 -n) heterocycloalkyl groups are preferred. Each ring can usually contain 1 to 4 heteroatoms The residue can be linked to the compound according to the invention via any carbon or heteroatom of the ring system which allows the formation of a stable bond.
  • heterocycloalkyl radicals are pyrrolinyl, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, indolinyl, Azetidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetr ahydrofuranyl, hexahydropyrimidinyl, hexahydropyridazinyl, dihydrooxazolyl, 1, 2-thiazinanyl-1, 1-dioxide, 1, 2,6-
  • acyl describes both saturated and mono- or polyunsaturated radicals of aliphatic carboxylic acids which are formed by removing the OH group of the carboxy group.
  • (C n -m) acyl groups are understood to mean those which contain n to m carbon atoms, where n and m stand for integers.
  • saturated radicals are preferably (C ⁇ - ⁇ o) acyl groups
  • unsaturated radicals are preferably (C 2 -i 2 ) acyl groups.
  • acyl includes both straight-chain and also branched radicals. Straight chain radicals are preferred
  • (C ⁇ - 8 ) acyl groups branched radicals preferably (C 3 - ⁇ o) acyl groups. Hydrogen atoms of these radicals can be partially or completely replaced by halogen atoms. Examples of these are the atoms of fluorine, chlorine, bromine and iodine. If all hydrogen atoms have been replaced by halogen atoms, the term "perhaloacyl" radical is used. Terms that consist of syllables or functional groups, the meaning of which is familiar from the specialist literature, and one or more of the syllables defined above, refer to radicals which are composed of the corresponding structural elements.
  • alkyloxy and “alkylthio” denote alkyl groups which are bonded to a further structural element via an oxygen or sulfur atom.
  • acylamino one of the hydrogen atoms of an amino group is replaced by an acyl group.
  • both X and Y stand for a nitrogen atom.
  • the radical A is unsubstituted or substituted by the radicals R 4 , R 5 and R 6, phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, furazanyl, thiazolyl, isothiazolyl, or pyrrolyl, wherein R 4 , R 5 and R 6 independently of one another for hydrogen (H), (C ⁇ . 8 ) alkyl, monofluoro (C ⁇ .
  • radical A is a phenyl or pyridyl group substituted by 1 to 3 substituents.
  • the radical R 1 has the meaning of amino, alkylamino, di (C ⁇ - 6) alkylamino, (C ⁇ .
  • R 1 are especially those which have properties of an electron donor.
  • Preferred radicals R 2 and R 3 are hydrogen, (C ⁇ - 6) AlkyI or (C 3 - 6) cycloalkyl.
  • Preferred radicals R 4 , R 5 and R 6 are hydrogen, fluorine, chlorine, bromine, (C ⁇ - 3 ) alkyl, Fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethyloxy, difluoromethyloxy, trifluoromethyloxy, and di (C ⁇ - 3 ) alkylamino.
  • the invention also includes pharmaceutically suitable derivatives of the compounds of formula (I).
  • a “pharmaceutically suitable derivative” is taken to mean salts and precursors of the compounds of the formula (I) which, after being administered to a patient, are converted directly or indirectly into one of the compounds according to the invention or one of their pharmacologically active metabolites Salts, acids and esters of the compounds according to the invention. Of particular importance are salts which are derived from pharmaceutically suitable inorganic or organic acids or bases.
  • Examples are the salts with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, oxalic acid, malonic acid, fumaric acid , Maleic acid, tartaric acid, citric acid, ascorbic acid and methanesulfonic acid.
  • acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, oxalic acid, malonic acid, fumaric acid , Maleic acid, tartaric acid, citric acid, ascorbic acid and methanesulfonic acid.
  • Precursors are compounds which, following simple chemical conversion, give compounds of formula (I) or one of their pharmacologically active metabolites.
  • Simple chemical transformations include hydrolysis, oxidation and reduction which e.g. can be done enzymatically or metabolically.
  • Compounds of this invention that have one or more asymmetric carbon atoms can exist as racemates or racemic mixtures, as isolated enantiomers, as diastereomeric mixtures, or as individual diastereomers.
  • Each stereogenic carbon atom can be in the R or S configuration or in a combination of both configurations.
  • Some of the compounds can also be in tautomeric forms.
  • the compounds according to the invention can be prepared, for example, according to the following reaction scheme:
  • a 3-oxo-propionic acid ester which can be prepared from the corresponding acetyl derivative and whose carbonyl group is bonded to the desired radical A is e.g. reacted with the salt of a primary amine such as N-methylammonium acetate to give the corresponding acrylic ester derivative. The latter is then reacted with the desired amino derivative of benzimidazole, benzoxazole or benzothiazole. The residue introduced by the primary amine is exchanged for the corresponding radical of the benzimidazole, benzoxazole or benzothiazole derivative.
  • Phosphorus oxychloride are halogenated at this position before being in a last one Step is reacted with the desired amine to give a compound according to the invention.
  • the intermediate products obtained after the individual process steps are, if necessary, purified.
  • the compounds produced in this way are active substances of interest, in particular for the preparation of an analgesic for the relief or treatment of pain. This effect can be determined using a simple test procedure in which the pain reactions of animals are observed and quantitatively evaluated.
  • the compounds according to the invention are operated as follows:
  • mice Male rats (strain: Chbb-THOM; weight: 200 to 300 g) are injected with 20 ⁇ l of a 2% formaldehyde solution in the plantar region of the right hind paw. Immediately afterwards, the number of flinches (twitches of the affected hind paw) and the duration of the licking of the affected paw are recorded for one hour. After five minutes, the values are summarized into epochs and time-effect curves for the flinches and the licking are created from these values. Typically, two phases of formalin action (flinches, licking) are observed: a first phase from 0 to 10 minutes and a second phase from 10 to 60 minutes.
  • the number of flinches and the duration of the leak decrease to zero for a short time (interphase).
  • the areas under the curves for the first and second phases are determined from the time-effect curves.
  • Five animals are usually used for control, placebo and substance dose.
  • the results of the substance doses are compared with those of the control, and ED 50 values are determined therefrom.
  • the ED 50 is the dose at which the control values are inhibited by 50%.
  • the antinociceptive activity of the compounds of this invention is based on blocking voltage-dependent N-type calcium channels.
  • the proof of this inhibitory effect is electrophysiologically using patch-clamp technique (see: Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches; Hamill et al .; Pflügers Archiv, 391. 1981, 85 - 100) on recombinant HEK 293 cells expressing the N-type calcium channel.
  • patch-clamp technique see: Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches; Hamill et al .; Pflügers Archiv, 391. 1981, 85 - 100
  • the compounds of Examples 4 and 6 showed IC 50 values of 3.6 and 2.0 / mol / L, respectively.
  • the compounds according to the invention can thus be used in processes which serve to alleviate or treat pain, a patient being administered a therapeutically effective amount of the compound according to the invention.
  • These can be acute pain, chronic pain, neuropathic pain or post-operative pain, as well as pain related to migraines, arthralgia, neuropathies, nerve injuries, diabetic neuropathy, neurodegeneration, neurotic skin diseases, stroke, bladder hypersensitivity, irritable bowel syndrome, Respiratory diseases such as asthma or chronic obstructive pulmonary disease, skin, eye or mucous membrane irritation, duodenal and gastric ulcers, stomach inflammation or other inflammatory diseases.
  • the compounds according to the invention For the treatment of pain, it can be advantageous to combine the compounds according to the invention with invigorating substances such as caffeine or other pain-relieving active substances. If suitable active substances are available for treating the cause of the pain, these can be combined with the compounds according to the invention. If other medical treatments are indicated regardless of the pain treatment, for example for hypertension or diabetes, the active substances required for this can also be combined with the compounds according to the invention.
  • the dose required to achieve an analgesic effect is expediently 0.01 to 3 mg / kg body weight, preferably 0.1 to 1 mg / kg, and 0.1 to 8 mg / kg body weight, preferably 0.5 to 3 mg / kg, respectively, in the case of intravenous administration 1 to 3 times a day.
  • the compounds of the formula (I) prepared according to the invention optionally in combination with other active substances, together with one or more inert customary carriers and / or diluents, for example with corn starch, Milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerin, water / sorbitol, water / polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethyl cellulose or fat-containing substances such as hard fat, or their suitable mixtures Work in galenical preparations such as tablets, coated tablets, capsules, powders, suspensions or suppositories.
  • inert customary carriers and / or diluents for example with corn starch, Milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water /
  • Example 1 3- ef ⁇ y / -9-mei' ⁇ y / am / ⁇ o-7- pyr / d / n-4-y / 3H- / m / / azo / 4 ? 5-f7c ⁇ / no /// 7

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Rheumatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne des composés hétéroaromatiques tricycliques de formule générale (I) et les sels de ces composés, les éléments structurels X, Y, A, R1 et R2 étant définis dans la description. L'invention concerne en outre la production de ces composés et leur utilisation comme médicaments, en particulier comme analgésiques.
PCT/EP2004/003626 2003-04-11 2004-04-06 Composes heteroaromatiques tricycliques Ceased WO2004089950A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10316659A DE10316659A1 (de) 2003-04-11 2003-04-11 Tricyclische Heteroaromatische Verbindungen
DE10316659.9 2003-04-11

Publications (1)

Publication Number Publication Date
WO2004089950A1 true WO2004089950A1 (fr) 2004-10-21

Family

ID=33039021

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2004/003626 Ceased WO2004089950A1 (fr) 2003-04-11 2004-04-06 Composes heteroaromatiques tricycliques

Country Status (2)

Country Link
DE (1) DE10316659A1 (fr)
WO (1) WO2004089950A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008143263A1 (fr) 2007-05-22 2008-11-27 Astellas Pharma Inc. Composé de tétrahydroisoquinoline 1-substituée
WO2016083490A1 (fr) * 2014-11-27 2016-06-02 Remynd Nv Composés pour le traitement de maladies associées à la substance amyloïde

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3947434A (en) * 1973-06-06 1976-03-30 Morton-Norwich Products, Inc. 9-(P-phenylazoanilino)-7-methyl-1H-imidazo[4,5-f]quinolines
EP0187705A2 (fr) * 1985-01-08 1986-07-16 Norwich Eaton Pharmaceuticals, Inc. Imidazo(4,5-f)quinolines utiles comme agents immunomodulateurs
WO2002036567A1 (fr) * 2000-11-06 2002-05-10 Astrazeneca Ab Antagonistes du canal calcium de type n pour traiter la douleur

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3947434A (en) * 1973-06-06 1976-03-30 Morton-Norwich Products, Inc. 9-(P-phenylazoanilino)-7-methyl-1H-imidazo[4,5-f]quinolines
EP0187705A2 (fr) * 1985-01-08 1986-07-16 Norwich Eaton Pharmaceuticals, Inc. Imidazo(4,5-f)quinolines utiles comme agents immunomodulateurs
WO2002036567A1 (fr) * 2000-11-06 2002-05-10 Astrazeneca Ab Antagonistes du canal calcium de type n pour traiter la douleur

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008143263A1 (fr) 2007-05-22 2008-11-27 Astellas Pharma Inc. Composé de tétrahydroisoquinoline 1-substituée
US8263607B2 (en) 2007-05-22 2012-09-11 Astellas Pharma Inc. 1-substituted tetrahydroisoquinoline compound
WO2016083490A1 (fr) * 2014-11-27 2016-06-02 Remynd Nv Composés pour le traitement de maladies associées à la substance amyloïde

Also Published As

Publication number Publication date
DE10316659A1 (de) 2004-10-28

Similar Documents

Publication Publication Date Title
EP0193056B1 (fr) Combinaison de la flupirtine avec des spasmolytiques à effet anticholinergique
EP0683780A1 (fr) Imidazopyridines et leur utilisation pour traiter des maladies gastro-intestinales
DE2365526A1 (de) Pharmazeutische zusammensetzung mit entzuendungshemmender, analgetischer, antipyretischer, hustenstillender und die geschwuerbildung hemmender wirkung
DE69908608T2 (de) Derivate von Imidazo[1,2-a]pyridin zur Behandlung von gastrointestinalen Krankheiten
WO1997031918A1 (fr) Sels de morphine et de diamorphine d'analgesiques anioniques non narcotiques du type des acides carboxyliques substitues
DE19831878C2 (de) Polycyclische Thiazolidin-2-yliden Amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
EP0006114B1 (fr) Acide 7-méthoxy-5-oxo-5H-thiazolo(2,3-b)quinazoline-2-carboxylique et ses sels pharmaceutiquement acceptables, leur procédé de préparation et médicaments les contenant
DD300105A5 (de) Neue R(-)3-Quinuliclidinol - Derivate
EP0621037B1 (fr) Composés pyrido-pyrimidinediones, leur préparation et leur utilisation pharmaceutique
DE10048715A1 (de) Verwendung von Aminosäure zur Behandlung von Schmerz
WO2000051602A1 (fr) Utilisation de systemes 2-amino-thiazole polycycliques pour la production de medicaments destines a la prophylaxie ou au traitement de l'obesite
WO2004089950A1 (fr) Composes heteroaromatiques tricycliques
DE1931240A1 (de) Aminoalkancarbonsaeuren
LV10618B (en) A novel derivatives of thienothiazine, method for preparing thereof and use
DE3844415A1 (de) Neue 3-piperidincarboxaldehydoxim-derivate, deren herstellungsverfahren und deren verwendung als arzneimittel
DE3026365C2 (fr)
EP0657459A1 (fr) Dérivés de thiénothiazine, procédé pour leur préparation et leur utilisation comme agents antiinglammatoires et analgésiques
US20040214833A1 (en) Tricyclic heteroaromatic compounds
DE2812585A1 (de) Chinazolin-derivate
DE68924545T2 (de) Verwendung von Chinolizin- und Chinolizinon-Derivaten zur Herstellung von Arzneimitteln.
DE2349493A1 (de) 2-(2-pyridyl)- omega-phenylalkylamine und verfahren zu ihrer herstellung
EP0525686A1 (fr) Amides d'acide diméthylacétylacétique, procédé pour leur préparation et compositions pharmaceutiques
DE2530005C3 (de) 6,11-Dihydrodibenzo [b,e] thiepin-Derivate und deren Salze, Verfahren zu ihrer Herstellung und diese Substanzen enthaltende pharmazeutische Zubereitungen
DE3310796A1 (de) Substituierte ethenylderivate von 1h-pyrazolo-(1,5-a)-pyrimidin, verfahren zur herstellung derselben, sowie diese enthaltende pharmazeutische praeparate
EP0001062B1 (fr) Dérivés de l'ergoline, leur procédé de préparation, compositions pharmaceutiques les contenant et leur mise en oeuvre de traitement thérapeutique

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase