WO2001085696A1 - Derives d'acide butenoique et utilisation de ces derniers dans le traitement de la rhinite - Google Patents
Derives d'acide butenoique et utilisation de ces derniers dans le traitement de la rhinite Download PDFInfo
- Publication number
- WO2001085696A1 WO2001085696A1 PCT/EP2001/005007 EP0105007W WO0185696A1 WO 2001085696 A1 WO2001085696 A1 WO 2001085696A1 EP 0105007 W EP0105007 W EP 0105007W WO 0185696 A1 WO0185696 A1 WO 0185696A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- phenyl
- methyl
- hydrogen
- alkyl
- formula
- Prior art date
Links
- 0 *C(*)[C@](C(*)=C(*)C(N)=O)N(*)C(*)=O Chemical compound *C(*)[C@](C(*)=C(*)C(N)=O)N(*)C(*)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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 carbon atoms
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
Definitions
- This invention relates to organic compounds and, in particular to their use as pharmaceuticals .
- the invention provides, in one aspect, use of a compound of formula I
- R 1 is phenyl that is unsubstituted or is substituted by 1, 2 or 3 substituents selected from the group halogen, C ⁇ -C -alkyl, trifluoromethyl, hydroxy and C ⁇ -C -alkoxy, R 2 is hydrogen or -C 7 -alkyl,
- R 3 is hydrogen, C ⁇ -C -alkyl or phenyl that is unsubstituted or is substituted by 1, 2 or 3 substituents selected from the group halogen, C ⁇ -C -alkyl, trifluoromethyl, hydroxy and C ⁇ -C - alkoxy,
- R 4 is phenyl that is unsubstituted or is substituted by 1 , 2 or 3 substituents selected from the group halogen, C ⁇ -C 7 -alkyl, trifluoromethyl, hydroxy and -Cy-alkoxy; or is naphthyl, 1H- indol-3-yl or l-C ⁇ -C -alkyl-indol-3-yl,
- R 5 and R 6 are each independently of the other hydrogen or C ⁇ -C 7 -alkyl, at least one of R 5 and R 6 being hydrogen, and R 7 is C -C 8 -cycloalkyl, D-azacycloheptan-2-on-3-yl or L-azacycloheptan-2-on-3-yl.
- the invention provides, in another aspect, a method of treating rhinitis in a subject, particularly a human subject, in need of such treatment, which comprises administering to said subject an effective amount of a compound of formula I as hereinbefore defined.
- Rhinitis to be treated in accordance with the invention may be allergic rhinitis, including perennial allergic rhinitis caused by allergens such as dust mites, cats, dogs, rodents, insects and food and seasonal allergic rhinitis caused by pollens from plants (including trees) such as ragweed, olive, birch, cedar, oak, elm, maple, juniper and grass and fern and fungal spores, non-allergic rhinitis, infective rhinitis, atrophic rhinitis, hypertrophic rhinitis, rhinitis caseosa, rhinitis sicca, rhinitis medicamentosa, purulent rhinitis, croupous rhinitis, fibrinous rhinitis and vasomotor rhinitis.
- allergens such as dust mites, cats, dogs, rodents, insects and food
- -Cy-alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl or n-heptyl, preferably C ⁇ -C 4 alkyl, especially methyl or ethyl, and more especially methyl.
- Halogen is, for example, fluorine, chlorine, bromine or iodine.
- Halophenyl is, for example, (fluoro-, chloro-, bromo- or iodo-)phenyl, preferably fluorophenyl or chlorophenyl, especially 4-fluorophenyl or 4-chlorophenyl, and more especially 4-chlorophenyl.
- Dihalophenyl is, for example, dichlorophenyl, difluorophenyl or chlorofluorophenyl, preferably dichlorophenyl or difluorophenyl, especially 3,4-dichlorophenyl or 3,4- difluorophenyl, and more especially 3,4-dichlorophenyl.
- Trihalophenyl is, for example, trifluorophenyl or trichlorophenyl.
- l-C C 7 -alkyl-indol-3-yl is, for example, l-methyl-indol-3-yl.
- C 3 -C 8 -Cycloalkyl - and analogously C 5 -C 7 -cycloalkyl - is in each case a cycloalkyl radical having the number of ring carbon atoms indicated.
- C -C 8 -Cycloalkyl is therefore, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, preferably cyclohexyl.
- L-aza- cycloheptan-2-on-3-yl corresponds to the group
- the compounds of formula I may be of formula IA
- Compounds of formula IA are usually preferred for use in accordance with the invention.
- Compounds of formula I having a basic group may, for example, form acid addition salts with suitable mineral acids, such as hydrohalic acids, sulfuric acid or phosphoric acid, for example hydrochlorides, hydrobromides, sulfates, hydrogen sulfates or phosphates.
- suitable mineral acids such as hydrohalic acids, sulfuric acid or phosphoric acid, for example hydrochlorides, hydrobromides, sulfates, hydrogen sulfates or phosphates.
- corresponding salts with bases are also possible, for example corresponding alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or organic amines, for example ammonium salts.
- the invention relates preferably to the use of compounds of formula I wherein
- R 1 is phenyl, 3,5-bistrifluoromethyl-phenyl or 3,4,5-trimethoxyphenyl,
- R 2 is hydrogen or -Cy-alkyl
- R 3 is hydrogen or phenyl
- R 4 is phenyl, halo-phenyl, dihalo-phenyl, trihalo-phenyl, 2-naphthyl, lH-indol-3-yl or 1- -
- R 5 and R 6 are each independently of the other hydrogen or -Cy-alkyl, at least one of R 5 and R 6 being hydrogen, and
- R 7 is Q 5 -C7cycloalkyl, D-azacycloheptan-2-on-3-yl or L-azacycloheptan-2-on-3-yl.
- the invention relates especially to the use of compounds of formula I wherein
- R 1 is 3,5-bistrifluoromethyl-phenyl
- R 2 is hydrogen, methyl or ethyl
- R 3 is hydrogen or phenyl
- R 4 is phenyl, 4-chlorophenyl, 4-fluorophenyl, 3,4-dichloro-phenyl, 3,4-difluoro-phenyl, 3- fluoro-4-chloro-phenyl, 3,4,5-trifluoro-phenyl, 2-naphthyl, lH-indol-3-yl or 1-methyl-indol-
- R 5 and R 6 are each independently of the other hydrogen or methyl, at least one of R 5 and R 6 being hydrogen, and
- R 7 is cyclohexyl, D-azacycloheptan-2-on-3-yl or L-azacycloheptan-2-on-3-yl.
- the invention relates more especially to the use of compounds of formula I wherein
- R 1 is 3,5-bistrifluoromethyl-phenyl
- R 2 is hydrogen or methyl
- R 3 is hydrogen or phenyl
- R 4 is phenyl, 4-chlorophenyl, 3,4-dichloro-phenyl, 2-naphthyl, lH-indol-3-yl or 1-methyl- indol-3-yl,
- R 5 and R 6 are hydrogen, and R 7 is cyclohexyl, D-azacycloheptan-2-on-3-yl or L-azacycloheptan-2-on-3-yl.
- the invention relates most importantly to the use of (4R)-4-[N'-methyl-N'-(3,5- bistrifluoromethylbenzoyl)amino]-4-(3,4-dichlorobenzyl)-but-2 -enoic acid N-[(R)-epsilon- caprolactam-3-yl]-amide, i.e. a compound of formula
- the compounds of formula I in free or pharmaceutically acceptable salt form, may be prepared as described in WO98/07694. As mentioned therein, they may be in the form of their hydrates and/or may include other solvents, for example solvents which may have been used for the crystallisation of compounds in solid form.
- the compounds of formula I may be obtained in the form of mixtures of stereoisomers, for example mixtures of diastereoisomers or mixtures of enantiomers, such as racemates, or possibly also in the form of pure stereoisomers.
- Mixtures of diastereoisomers obtainable in accordance with the process or by some other method can be separated in customary manner into mixtures of enantiomers, for example racemates, or into individual diastereoisomers, for example on the basis of the physico-chemical differences between the constituents in known manner by fractional crystallisation, distillation and/or chromatography.
- the more active isomer is isolated.
- Mixtures of enantiomers, especially racemates, obtainable in accordance with the process or by some other method can be separated into the individual enantiomers by known methods, for example by recrystallisation from an optically active solvent, with the aid of microorganisms, by chromatography and/or by reaction with an optically active auxiliary compound, for example a base, acid or alcohol, to form mixtures of diastereoisomeric salts or functional derivatives, such as esters, separation thereof and freeing of the desired enantio- mer.
- an optically active auxiliary compound for example a base, acid or alcohol
- compounds of formula I in free form or in pharmaceutically acceptable salt form, may be administered by any appropriate route, for example orally, e.g. in tablet or capsule form, parenterally, for example in the form of an injectable solution or suspension, or intranasally, for example in the form of an aerosol or other atomisable formulation using an appropriate intranasal delivery device, e.g. a nasal spray such as those known in the art.
- an appropriate intranasal delivery device e.g. a nasal spray such as those known in the art.
- the compound of formula I in free or salt form may be administered in a pharmaceutical composition together with a pharmaceutically acceptable diluent or carrier.
- a pharmaceutical composition may be as described in WO98/07694, for example tablets, capsules, injection solutions, infusion solutions or inhalation suspensions as described in Examples A to E of WO98/07694, or may be prepared using other formulating ingredients and techniques known in the art.
- the dosage of the compound of formula I in free or salt form can depend on various factors, such as the activity and duration of action of the active ingredient, the severity of the condition to be treated, the mode of administration, the species, sex, age and weight of the subject and/or its individual condition.
- the daily dose for administration for example oral administration, to a warm-blooded animal weighing about 75 kg is estimated to be from approximately 1 mg to approximately 1000 mg, especially from approximately 5 mg to approximately 200 mg. That dose may be administered, for example, in a single dose or in several part doses of, for example, from 10 to 100 mg.
- a compound of formula I in the treatment of rhinitis may be demonstrated in an animal model of Substance P - or capsaicin - induced nasal extravasation, for example as hereinafter described in Example 2, or by the inhibitory effect of a compound of formula I on the increase in permeability of the nasal cavity in guinea-pigs following aerosol exposure to ovalbumin using a nose-only exposure system.
- (4R,S)-N'-methyl-amino-4-(3,4-dichlorobenzyl)-but-2 -enoic acid-N-[(S)-epsilon-caprolactam- 3-yl]-amide is prepared as follows: a) Racemic N-Methyl- N-tert-butyloxycarbonyl-3.4-dichlorophenyl-alanine-methyl ester: To a solution of freshly prepared lithium diisopropylamide (from 13.9ml n-BuLi and 3.2ml diisopropylamine in 50ml dry THF), a solution of 4g N-methyl-N-tert-butyloxycarbonyl- glycine-methyl ester (in 15 ml THF) is slowly added at -78°C.
- Male Hartley guinea-pigs (330-420g body weight, SLC, Japan) are housed in groups of 3 to 5, and receive water and food ad libitum. They are anaesthetized by an intraperitoneal injection of phenobarbitone (100 mg/kg, Wako, Japan), supplemented with an intraperitoneal injection of pentobarbital (30 mg/kg, Abbott, USA), and ventilated mechanically (0.5 litre air/min, 60 Hz). The oesophagus is ligated with a thread and the mouth is closed by cotton containing paraffin (Wako, Japan) to interrupt perfusate flow across the cavities.
- phenobarbitone 100 mg/kg, Wako, Japan
- pentobarbital 30 mg/kg, Abbott, USA
- the oesophagus is ligated with a thread and the mouth is closed by cotton containing paraffin (Wako, Japan) to interrupt perfusate flow across the cavities.
- a polyethylene cannula is inserted into the nasopharynx from the side of the larynx and the other end of the cannula is connected to a perfusion pump. Saline is perfused at a constant rate (0.25 ml/minute).
- a solution containing a certain concentration of substance P (Sigma, USA) is perfused for 10 minutes instead of saline, 10 minutes after an intravenous injection of Evans blue dye (2%, 1 ml/kg, Wako, Japan).
- the leakage fluid from the nasopharynx is collected at 10 minute intervals for 60 minutes after initiation of substance P challenge.
- the perfusate is centrifuged (1250 g for 10 minutes, CR 5DL, Hitachi, Japan).
- the amount of Evans blue dye in the supernatant is measured at 620 nm in a microplate absorbance spectrophotometer (M-Emax, Wako, Japan).
- the concentration of Evans blue dye is calculated as ⁇ g/ml according to the serial dilutions of a standard Evans blue dye.
- Either vehicle alone or containing a compound of formula If in an amount of 1 ml/kg is given by gavage 2 hours prior to the initiation of substance P perfusion or of capsaicin application.
- the vehicle consists of 1 % tragacanth gum in water.
- the total amount of Evans blue dye is calculated with accumulation in 60 minutes after initiation of substance P challenge and in 70 minutes after capsaicin application.
- a Bonferroni multiple comparison test is used to assess the statistical significance of difference after a one-way analysis of variance.
- unpaired Student's t-test is used to assess the statistical significance of difference between the saline perfusion and the substance P perfusion/capsaicin application of vehicle pre-treated groups: a value of p ⁇ 0.05 is considered significant.
- Topical application of capsaicin induces an increase in nasal permeability in a concentration-dependant manner, expressed as increasing concentrations of Evans blue dye.
- concentration-dependant manner expressed as increasing concentrations of Evans blue dye.
- the responses are accumulated as total Evans blue dye amount, the response is seen to occur in a concentraiton-dependant manner and a significant difference is observed at the highest concentration, 10 mg ml. From these observations, 10 mg/ml capsaicin is selected for further study.
- the response following capsaicin application is not significantly increased. Capsaicin- induced nasal extravasation is inhibited. The estimated ED 50 value is 1.02 mg kg.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne l'utilisation d'un composé selon la formule (I), en forme libre ou sous forme d'un sel pharmaceutiquement acceptable pour la préparation d'un médicament permettant de traiter la rhinite. Dans la formule, R1 représente phényle qui n'est pas substitué ou est substitué par 1, 2 ou 3 substituants sélectionnés dans le groupe halogène, alkyle C1-C7, trifluorométhyle, hydroxy et alcoxy C1-C7, R2 représente hydrogène ou alkyle C1-C7, R3 représente hydrogène, alkyle C1-C7 ou phényle non substitué ou substitué par 1, 2 ou 3 substituants sélectionnés dans le groupe halogène, alkyle C1-C7, trifluorométhyle, hydroxy et alcoxy C1-C7, R4 représente phényle qui n'est pas substitué ou est substitué par 1, 2 ou 3 substituants sélectionnés dans le groupe halogène, alkyle C1-C7 ; trifluorométhyle, hydroxy et alcoxy C1-C7ou naphthyle, 1H-indol-3-yle ou 1- alkyle C1-C7 -indol-3-yle, R5 et R6 représentent chacun séparément de l'autre hydrogène ou alkyle C1-C7, au moins un élément parmi R5 et R6 étant de l'hydrogène, et R7 représente cycloalkyle C3-C8, D-azacycloheptane-2-on-3-yle ou L-azacycloheptane-2-on-3-yle.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001254825A AU2001254825A1 (en) | 2000-05-05 | 2001-05-03 | Butenoic acids derivatives and their use in the treatment of rhinitis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0010958.7 | 2000-05-05 | ||
GBGB0010958.7A GB0010958D0 (en) | 2000-05-05 | 2000-05-05 | Organic compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001085696A1 true WO2001085696A1 (fr) | 2001-11-15 |
Family
ID=9891095
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2001/005007 WO2001085696A1 (fr) | 2000-05-05 | 2001-05-03 | Derives d'acide butenoique et utilisation de ces derniers dans le traitement de la rhinite |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU2001254825A1 (fr) |
GB (1) | GB0010958D0 (fr) |
WO (1) | WO2001085696A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009533369A (ja) * | 2006-04-13 | 2009-09-17 | ノバルティス アクチエンゲゼルシャフト | サブスタンスpアンタゴニストとして有用なアシルアミノアルケニレンアミドの合成 |
EP2216025A2 (fr) | 2002-02-08 | 2010-08-11 | Novartis AG | Utilisation de derives d'amide d'acylaminoalkenylene dans le côlon irritable et la dyspepsie fonctionelle |
US11141312B2 (en) | 2007-09-07 | 2021-10-12 | Mati Therapeutics Inc. | Lacrimal implant detection |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996026183A1 (fr) * | 1995-02-22 | 1996-08-29 | Novartis Ag | Composes 1-aryl-2-acylamino-ethane et leur utilisation en tant qu'antagonistes des neurokinines et notamment des neurokinines 1 |
EP0747055A2 (fr) * | 1995-06-09 | 1996-12-11 | Eli Lilly And Company | Utilisation d'antagonistes du récepteur de tachykinine pour le traitement du rhume et de la rhinite allergique |
WO1998007694A1 (fr) * | 1996-08-22 | 1998-02-26 | Novartis Ag | Derives d'acylaminoalkenylene comme antagonistes de nk1 et nk2 |
WO2000014109A1 (fr) * | 1998-09-08 | 2000-03-16 | Menarini Ricerche S.P.A. | Produits de base presentant une activite antagoniste sur le recepteur de la nk-1 et leur utilisation dans des preparations pharmaceutiques |
-
2000
- 2000-05-05 GB GBGB0010958.7A patent/GB0010958D0/en not_active Ceased
-
2001
- 2001-05-03 AU AU2001254825A patent/AU2001254825A1/en not_active Abandoned
- 2001-05-03 WO PCT/EP2001/005007 patent/WO2001085696A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996026183A1 (fr) * | 1995-02-22 | 1996-08-29 | Novartis Ag | Composes 1-aryl-2-acylamino-ethane et leur utilisation en tant qu'antagonistes des neurokinines et notamment des neurokinines 1 |
EP0747055A2 (fr) * | 1995-06-09 | 1996-12-11 | Eli Lilly And Company | Utilisation d'antagonistes du récepteur de tachykinine pour le traitement du rhume et de la rhinite allergique |
WO1998007694A1 (fr) * | 1996-08-22 | 1998-02-26 | Novartis Ag | Derives d'acylaminoalkenylene comme antagonistes de nk1 et nk2 |
WO2000014109A1 (fr) * | 1998-09-08 | 2000-03-16 | Menarini Ricerche S.P.A. | Produits de base presentant une activite antagoniste sur le recepteur de la nk-1 et leur utilisation dans des preparations pharmaceutiques |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2216025A2 (fr) | 2002-02-08 | 2010-08-11 | Novartis AG | Utilisation de derives d'amide d'acylaminoalkenylene dans le côlon irritable et la dyspepsie fonctionelle |
JP2009533369A (ja) * | 2006-04-13 | 2009-09-17 | ノバルティス アクチエンゲゼルシャフト | サブスタンスpアンタゴニストとして有用なアシルアミノアルケニレンアミドの合成 |
US8008479B2 (en) | 2006-04-13 | 2011-08-30 | Novartis Ag | Organic compounds |
US11141312B2 (en) | 2007-09-07 | 2021-10-12 | Mati Therapeutics Inc. | Lacrimal implant detection |
Also Published As
Publication number | Publication date |
---|---|
AU2001254825A1 (en) | 2001-11-20 |
GB0010958D0 (en) | 2000-06-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2021206876A1 (fr) | Inhibiteurs de la réplication de norovirus et de coronavirus | |
US5688946A (en) | Amino acid derivatives having renin inhibiting activity | |
CH651548A5 (fr) | Derives mercapto-acyles de diverses prolines 4-substituees a action anti-hypertensive. | |
CA2012306A1 (fr) | Derives d'acides amines | |
FR2602142A1 (fr) | Utilisation en therapeutique des antagonistes des recepteurs serotoninergiques 5ht3 | |
EP0031741A1 (fr) | Nouveaux iminoacides substitués, leurs procédés de préparation et leur emploi comme inhibiteurs d'enzymes | |
FR2518088A1 (fr) | Nouveaux derives d'aminoacides, et leur application therapeutique | |
EP0049658A1 (fr) | Iminodiacides substitués, leur préparation et compositions pharmaceutiques les contenant | |
CA2095009A1 (fr) | Derives imines cycliques | |
CZ283602B6 (cs) | Pyrrolidinové deriváty, způsob jejich přípravy a léčiva tyto deriváty obsahující | |
DE3246503A1 (de) | Derivate der cis, endo-2-azabicyclo-(5.3.0)-decan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung | |
HUP0101281A2 (hu) | Glicin transzport inhibitor hatású difenil-piperidin-butánamid-származékok, eljárás előállításukra, alkalmazásuk gyógyszerkészítmények előállítására és a vegyületeket tartalmazó gyógyszerkészítmények | |
EP0354522A1 (fr) | Utilisation de dérivés de l'acide alpha-aminoboronique pour la prévention et le traitement des maladies virales | |
LU85826A1 (fr) | Alpha-aminoacides substitues,leur fabrication et compositions pharmaceutiques les contenant | |
EP0310918A2 (fr) | Dérivés peptidiques d'acides aminés | |
TW200524578A (en) | Protease inhibitors | |
DE2658254A1 (de) | Peptidcarbazate | |
WO2001085696A1 (fr) | Derives d'acide butenoique et utilisation de ces derniers dans le traitement de la rhinite | |
HU199858B (en) | Process for producing piperazinecarboxylic acid derivatives and pharmaceutical compositions comprising such compound | |
HU184610B (en) | Process for producing immunostimulating n-substituted-aziridine-2-carboxylic acid derivatives | |
ES2965293T3 (es) | Compuestos y composiciones que comprenden los mismos para el tratamiento de la hipertensión o falla cardíaca | |
DE69910787T2 (de) | Neuartige, pharmazeutisch aktive verbindung | |
CH653017A5 (fr) | Derives s-acyles d'acides mercaptoacylamines ayant une activite inhibitrice de l'enzyme de conversion de l'angiotensine. | |
US20070293473A1 (en) | Use of acylaminoalkenylene-amide derivatives in functional motility disorders of the viscera | |
SK161197A3 (en) | Use of pyrrolidine derivatives for treating alcoholism |
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 BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EE 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 NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: JP |