EP0250530A1 - Nouveaux derives aryles - Google Patents

Nouveaux derives aryles

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Publication number
EP0250530A1
EP0250530A1 EP19870900230 EP87900230A EP0250530A1 EP 0250530 A1 EP0250530 A1 EP 0250530A1 EP 19870900230 EP19870900230 EP 19870900230 EP 87900230 A EP87900230 A EP 87900230A EP 0250530 A1 EP0250530 A1 EP 0250530A1
Authority
EP
European Patent Office
Prior art keywords
acid
formula
compound
hydrogen
naphthyloxy
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Withdrawn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
EP19870900230
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German (de)
English (en)
Inventor
Geoffrey Kneen
William Paul Jackson
Peter John Islip
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.)
Wellcome Foundation Ltd
Original Assignee
Wellcome Foundation Ltd
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Filing date
Publication date
Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd
Publication of EP0250530A1 publication Critical patent/EP0250530A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids

Definitions

  • the present invention relates to novel compounds, to methods of preparing such compounds, compositions containing them and to their use in medicine and in other applications.
  • Certain agents such as are described in European patent specification no. FP 0 055 418 are dual inhibitors of the lipoxygenase and cyclo-oxygenase enzymes of the mammalian arachidonic acid metabolism and have been found to exhibit anti-inflammatory and related activities.
  • Other compounds which have been described as lipoxygenase and/or cyclo-oxygenase inhibitors include certain naphthyloxy derivatives (eg as described in US patent speci fication 3 740 437 or in Proc. Ann. Symp. Inst. Basic Med. Sci, Royal College of Surgeons of England, October 1982, pp 263-274.
  • Compounds described in the latter reference include the compound known as nafazatrom.
  • k 0 or 1
  • one of m and n is 0 and the other is 1;
  • Ar represents a phenyl or a naphthyl group, both of which optionally may be substituted by one or more substituents selected from C 1-4 alkyl (which may itself optionally be substituted by one or more halogen atoms), C 1 alkoxy, halo, nitro, amino, carboxy, C 1-4 alkoxycarbonyl and hydroxy;
  • X represents oxygen or sulphur
  • Y is C 1-6 alkylene; and R 1 and R 2 are independently selected from hydrogen and C 1-4 alkyl; and salts thereof ;
  • R 1 and R 2 are both hydrogen
  • Y represents -(CH 2 ) 2 - or when Y has 4 carbon atoms, Y represents -(CH 2 ) 4 -.
  • alkyl and alkyl-containing moieties can be either straight or branched.
  • the salts of the compounds of formula (I) are those salts which are physiologically acceptable.
  • non-physiologically acceptable salts are included within the ambit of the present invention, either for use in non-medical applications such as further described hereinbelow, or as may be used in the preparation of compounds of formula (I) and their physiologically acceptable salts.
  • pro-drugs of the above defined compounds that is to say compounds which are metabolised in vivo to produce the compounds of formula (I) and their physiologically acceptable salts.
  • Ar represents phenyl optionally substituted by one or more substituents selected from C 1-4 alkyl (which may itself optionally be substituted by one or more halogen atoms), C 1-4 alkoxy, halo, nitro, amino, carboxy, C 1-4 alkoxycarbonyl and hydroxy;
  • Ar represents naphthyl optionally substituted by one or more substituents selected from C 1- 4 alkyl (which may itself optionally be substituted by one or more halogen atoms), C 1-4 alkoxy, halo, nitro, amino, carboxy, C 1-4 alkoxycarbonyl and hydroxy;
  • Examples of compounds of formula (I) include the following and salts thereof :
  • the present invention provides the compounds of formula (I') as defined hereinbeiow and their physiologically acceptable salts for use in a method of treatment of the human or animal body by therapy, or of diagnosis.
  • formula (I')
  • k 0 or 1
  • one of m and n is 0 and the other is 1;
  • Ar represents a phenyl or a naphthyl group, both of which optionally may be substituted by one or more substituents selected from C 1 -4 alkyl (which may itself optionally be substituted by one or more halogen atoms), C 1-4 lkoxy, halo, nitro, amino, carboxy, C 1-4 alkoxycarbonyi and hydroxy;
  • X represents oxygen or sulphur
  • Y is C 1 -6 alkylene
  • R 1 and R 2 are independently selected from hydrogen and C 1 -4 alkyl; and salts thereof.
  • the present invention also provides any compound of formula (I) (as hereinbefore defined) or physiologically acceptable salt thereof for use as an inhibitor of the lipoxygenase and/or cyclo-oxygenase enzymes of the mammalian arachidonic acid metabolism, to methods of inhibition of such enzyme(s) by administration to a mammal of a lipoxygenase and/or cyclo-oxygenase (as appropriate) inhibiting amount of any such compound or salt, and to use of any such compound or salt in the manufacture of lipoxygenase and/or cyclo-oxygenase inhibitor (as appropriate) agents.
  • any compound of formula (I) as hereinbefore defined
  • physiologically acceptable salt thereof for use as an inhibitor of the lipoxygenase and/or cyclo-oxygenase enzymes of the mammalian arachidonic acid metabolism
  • the present invention also provides any compound of formula (D (as hereinbefore defined) or physiologically acceptable salt thereof, for use as a medical therapeutic and/or prophylactic agent, to methods of medical therapeutic and/or prophylactic treatment by administration to a mammal of a medically therapeutic and/or prophylactic (as appropriate) effective amount of any such compound or salt, and to use of any such compound or salt in the manufacture of medical therapeutic and/or prophylactic (as appropriate) agents.
  • the kinds By virtue of their enzyme inhibitory effects, the compounds of formula (I') and salts thereof are also useful for controlling the processes of growth and decay in plants.
  • the present invention also provides the compounds of formula (I') and their salts for use in a method of regulating the growth of, or delaying senescence in vegetable matter by application to said matter of an effective amount of a compound of formula (I' ) or a salt thereof.
  • senescence refers to the process whereby plant matter decays, especially after being picked, cut or otherwise removed from its normal growing environment.
  • Vegetable matter includes trees, shrubs, flowers and edible vegetables and other food crops.
  • the above method is particularly applicable to flowers intended for decorative or display purposes such as carnations, crysanthemums, daisies, begonias, etc. These include perennial annual and biannual flowers, for example those that grow from bulbs (eg dahlias) or from seed (eg marigolds).
  • the method is also especially suited to use with decorative shrubs and trees, for example those which are displayed when cut, such as Christmas trees.
  • the compound of formula (I') and their salts may also be used for the preservation of picked fruits.
  • a suitable dose of a compound of formula (I') for a mammal suffering from an inflammatory, painful or pyretic condition as defined hereinbefore is 0.1 ⁇ g500mg of base per kilogram bodyweight.
  • the dose may be in the range 0.5 to 500 mg of base per kilogram bodyweight, the most preferred dosage being 0.5 to 50 mg/kg of mammal bodyweight for example 5 to 25 mg/kg; administered two or three times daily.
  • topical administration eg.
  • a suitable dose may be in the range 0.lng - 100 ⁇ g of base per kilogram, typically about 0.1 ⁇ g/Kg.
  • medical therapy and prophylaxis pertinent to the foregoing and there fore in that sense comprising part of the present invention, are elaborated by way of example in the following paragraphs which are not intended to be construed as in any way limiting the scope of these aspects of said invention.
  • said compounds and salts fi nd application in the treatment and/or prophylaxis of any condition where a lipoxygenase inhibitor is indicated, especially spasmogenic and allergic conditions and tumours.
  • said compounds and salts find application in the treatment and/or prophylaxis of any condition where a cyclo-oxygenase inhibitor is indicated, especially pyresis and pain.
  • said compounds and salts find application in the treatment and/or prophylaxis of any condition where a dual lipoxygenase/cycio-oxygenase inhibitor is indicated, especially any condition involving blood platelet aggregation or inflammation.
  • the compounds and salts are particularly suited to the treatment and/or prophylaxis of conditions associated with infiltration of leucocytes into inflamed tissue.
  • Fxamples of the aforesaid spasmogenic conditions are those involving smooth muscle tissue, especially airway smooth muscle constriction such as intrinsic asthma (including intrinsic or idiopathic bronchial asthma and cardiac asthma), bronchitis and arterial smooth muscle constriction such as coronary spasm (including that associated with myocardiai infarction, which may or may not lead to left ventricular failure resulting in cardiac asthma) and cerebral spasm or 'stroke'.
  • Other examples include bowel disease caused by abnormal colonic muscular contraction such as may be termed 'irritable bowel syndrome', 'spastic colon' or 'mucous colitis'.
  • aforesaid allergic conditions are extrinsic asthma (from which it will be appreciated that said compounds and salts are particularly favourable as anti-asthmatic agents), ailergic skin diseases such 83 eczema having a total or partial allergic origin, allergic bowel disease (including coeiiac disease) and allergic eye conditions such as hayfever (which may additionally or alternatively affect the upper respiratory tract) and allergic conjunctivitis.
  • aforesaid tumours are skin neoplasms, both benign and malignant.
  • Examples of the aforesaid pyretic and painful conditions include fever associated with infections, trauma and injury, malignant disease, and diseases affecting the immune system (including anto-immune diseases).
  • Examples of the aforesaid conditions involving blood platelet aggregation are those resulting from thrombosis, including 'stroke' having a total or partial thrombotic origin, coronary thrombosis, phlebitis and phlebothrombosis (the latter two conditions also possibly being associated with inflammation).
  • Examples of the aforesaid conditions involving inflammation are inflammatory conditions of the lung, joints, eye, bowel, skin and heart.
  • Inflammatory lung conditions which may be so treated and/or prevented include asthma and bronchitis (vide supra) and cystic fibrosis (which may also or alternatively involve the bowel or other tissue).
  • Inflammatory joint conditions which may be so treated and/or prevented include rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions.
  • Inflammatory eye conditions which may be so treated and/or prevented include uveitis (including ulceris) and conjunctivitis (vide supra).
  • Inflammatory bowel conditions which may be so treated and/or prevented include Crohn's disease and ulcerative colitis.
  • Inflammatory skin diseases which may be so treated and/or prevented include those associated with cell proliferation, such as psoriasis and eczema (vide supra) and dermatitis (whether or not of allergic origin).
  • Inflammatory conditions of the heart which may be so treated and/or prevented include coronary Infarct damage.
  • tissue necrosis of chronic inflammation and tissue rejection following transplant surgery include tissue necrosis of chronic inflammation and tissue rejection following transplant surgery.
  • a suitable anti-asthmatic dose of a compound of formula (I') is 1 mg to 10 mg of base per kilogram, the most preferred dosage being 1 mg to 5 mg/kg of mammal bodyweight, for example from 1 to 2 mg/kg.
  • an active ingredient While it is possible for an active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation comprising a compound of formula (I') or a pharmacologically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier therefor.
  • a pharmaceutical formulation comprising a compound of formula (I') or a pharmacologically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier therefor.
  • the active ingredient comprises from 0.1% to 99.9% by weight of the formulation.
  • unit doses of a formulation contain between 0,1 mg and 1 g of the active ingredient.
  • the active ingredient preferably comprises from 1% to 2% by weight of the formulation but the active ingredient may comprise as much as 10% w/w.
  • Formulations suitable for nasal or buccal administration, (such as self-propelling powder dispensing formulations described hereinafter), may comprise 0.1 to 20% w/w, for example 2% w/w of active ingredient.
  • the formulations, both for veterinary and for human medical use, of the present invention comprise an active ingredient in association with a pharmaceutically acceptable carrier therefor and optionally other therapeutic ingredient(s).
  • the carrier(s) must be 'acceptable' in the sense of being compatible with the other ingredients of the formulations and not deleterious to the recipient thereof.
  • the formulations include those in a form suitable for oral, ophthalmic, rectal, parenteral (including subcutaneous, intramuscular and intravenous), intra-articular, topical, nasal or buccal administration.
  • the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing the active ingredient into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product into the desired formulation.
  • Formulations of the present invention suitable for oral administration may be in the form of discrete units such as capsules, cachets, tablets or lozenges, each containing a predetermined amount of the active ingredient; in the form of a powder or granules; in the form of a solution or a suspension in an aqueous liquid or non-aqueous liquid; or in the form of an oil-in-water emulsion or a water-in-oil emulsion.
  • the active ingredient may also be in the form of a bolus, electuary or paste.
  • a tablet may be made by compressing or moulding the active ingredient optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent.
  • Moulded tablets may be made by moulding, in a suitable machine, a mixture of the powdered active ingredient and a suitable carrier moistened with an inert liquid diluent.
  • Formulations for rectal administration may be in the form of a suppository incorporating the active ingredient and a carrier such as cocoa butter, or in the form of an enema.
  • Formulations suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active ingredient which is preferably isotonic with the blood of the recipient.
  • Formulations suitable for intra-articular administration may be in the form of a sterile aqueous preparation of the active ingredient which may be in microcrystalline form, for example, in the form of an aqueous microcrystalline suspension.
  • Liposomal formulations or biodegradable polymer systems may also be used to present the active ingredient for both intra-articular and ophthalmic administration.
  • Formulations suitable for topical administration include liquid or semi-liquid preparations such as liniments, lotions, applications; oil-in-water or water-in-oil emulsions such as creams, ointments or pastes; or solutions or suspensions such as drops.
  • the active ingredient may be presented in the form of aqueous eye drops as, for example, a 0.1 - 1.0% solution.
  • Formulations suitable for administration to the nose or buccal cavity include powder, self-propelling and spray formulations such as aerosols and atomizers.
  • the formulations, when dispersed, preferably have a particle size in the range of 10 to 200 ⁇ .
  • Formulations of the present invention may also be in the form of an aqueous or dilute alcoholic solution, optionally a sterile solution, of the active ingredient for use in a nebuliser or atomiser, wherein an accelerated air steam is used to produce a fine mist consisting of small droplets of the solution.
  • Such formulations usually contain a flavouring agent such as saccharin sodium and a volatile oil.
  • a buffering agent and a surface active agent may also be included in such a formulation which should also contain a preservative such as methylhydroxybenzoate.
  • formulations suitable for nasal administration include a coarse powder having a particle size of 20 to 500 microns which is administered in the manner in which snuff is taken i.e. by rapid inhalation through the nasal passage from a container of the powder held close up to the nose.
  • the formulations of this invention may include one or more additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives eg. methylhydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • additional ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives eg. methylhydroxybenzoate (including anti-oxidants), emulsifying agents and the like.
  • Any other therapeutic ingredient may comprise one or more of the following: antibiotic, anti-fungal and anti-viral agents.
  • the compounds of formula (I') and their salts are preferably presented in a suitable compostion, optionally containing one or more other agents for enhancing the freshness of the plants.
  • suitable compositions include solutions and suspensions of the compound in a suitable medium such as an aqueous medium.
  • compositions may be applied by immersing part (eg the cut end) or whole of the plant or by spraying the plants before ar after cutting or picking, or by application to the root structure before or after picking.
  • the compounds may also be applied by being spread on the soil prior to cutting or picking and conveyed to the plant roots by rainwater, or by other watering means.
  • the compounds When applied in aqueous solution, the compounds may be presented in a concentration of from 1 ⁇ M to 1M, for example 100 ⁇ M to 100mM. A typical concentration might be about 1mM.
  • the compounds of formula (I) and their salts may be prepared by the allowing process which constitutes a further aspect of the present invention:- a) for the preparation of compounds of formula (I) wherein R 1 represents hydrogen, reaction of a compound of formula (II)
  • R 3 and R 4 are a group of formula Ar-(X) k -Y-; Ar, X, Y and k being as defined in formula (I), and the other is a group of formula R 2 as defined in formula (I), and Z is an appropriate protecting group) with an agent or agents serving to effect removal of the protecting group Z;
  • R 3 and R 4 are as hereinbefore defined and X represents an appropriate leaving group
  • R 5 represents a group of formula Ar-(X) k -Y-; Ar, X, Y and k being as defined in formula (I)) with Piloty's acid, ie. the compound of formula PhSO 2 NHOH;
  • protecting groups include benzoyl, acetyl, benzyl, trityl and tetrahydropyranyl.
  • the protecting group may be removed by treatment with acid or base or by hydrogenation,as appropriate.
  • the leaving group may for example be a halogen (eg chlorine, bromine or iodine), alkoxy or alkoxycarbonyloxy.
  • a halogen eg chlorine, bromine or iodine
  • Process (c) is desirably ejected in the presence of a base such as an alkali metal hydroxide or alkoxide, eg sodium hydroxide or sodium methoxide.
  • a base such as an alkali metal hydroxide or alkoxide, eg sodium hydroxide or sodium methoxide.
  • Optional conversion (i) may for example be effected by reaction with an appropriate alkyl halide or sulphate in the presence of a mild base.
  • Optional conversion (ii) conveniently may be effected by reaction with an appropriate organic or mineral acid, or with a base.
  • Salts derived from acids include the acetate, adipate, alginate, aspartate, benzoate, benzenesulphonate, bisulphate, butyrate, citrate, camphorate, camphorsulphonate, cyclopentanepropionate, digluconate, dodecylsulphate, ethanesulphonate, fumarate, glucoheptanoate, glycerophos-phate, hemisulphate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2- hydroxyethanesulphonate, lactate, maleate, methanesulphonate, 2- naphthaienesulphonate, nicotinate, oxalate, palmoate, pectinate, persulphate, 3-phenyl-proprionate, picrate, pivalate, proprionate, succinate, tartrate, thiocyanate, tosylate, and
  • Base salts include ammonium salts, alkali metal salts such as sodium and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamine salts, N-methyl-D-glucamine, and salts with amino acids such as arginine and lysine.
  • Quaternary ammonium salts can be formed where a nitrogen-containing group is present, for example by reaction with lower alkyl halides, such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulphates, long chain haiides such as decyl, lauryl, myristyi and stearyl chlorides, bromides and iodides, aralkyl haiides like benzyl and phenethyl bromides.
  • lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides
  • dialkyl sulphates long chain haiides such as decyl, lauryl, myristyi and stearyl chlorides, bromides and iodides, aralkyl haiides like benzyl and phenethyl bromides.
  • (k) a method of regulating the growth of, or delaying senescence in vegetable matter by application to said matter of an effective amount of a compound of formula (I') or a salt thereof.
  • Triethylamine (2.8 ml) was added to a solution of 3-(2-naphthyloxy)propanoic acid (4.32g) in dry tetrahydrofuran (25 ml) at 0°, under nitrogen. The mixture was stirred and ethyl chioroformate (2 ml) was added dropwise over 10 mins., the temperature then being maintained at 0° for a further 15 mins. The reaction mixture was treated with a mixture containing N-methylhydroxylarnine hydrochloride (5.1g), triethylamine (8.4 ml), tetrahydrofuran (15 ml) and water (10 ml) which had previously been cooled to 0°.
  • Triethylamine (2.8 ml) was added to a solution of 2-(1-naphthyloxy)acetic acid (4.04 g) in dry tetrahydrofuran (25 ml) at 0°, under nitrogen. The mixture was stirred and ethyl chloroformate (2 ml) was added dropwise over 10 mins., the temperature then being maintained at 0° for a further 15 mins. The reaction mixture was treated with a mixture containing N-methylhydroxylamine hydrochloride (5.1g), triethylamine (8.4 ml), tetrahydrofuran (15 ml) and water (10 ml) which had previously been cooled to 0°.
  • Bromoacetal (4.925g) was added over 5 min to a solution of 2-thiona ⁇ hthol (4.4g) and potassium t-butoxide (3.22g) in dimethyl sulphoxide (25ml) at room temperature under nitrogen. The mixture was stirred for 2 h, then left overnight. Addition of water, and isolation with ether afforded the acetal (6.5g) as an oil. Without purification, the acetal was stirred and heated under reflux for 4 h with acetone (70ml) and 2M hydrochloric acid (20ml) under nitrogen. Evaporation, and isolation with ether furnished 2-(2-naphthylthio) acetaldehyde (ca 4.75g) as a yellow oil.
  • N-diacetyl compound was stirred in methanol (100ml) with potassium carbonate (2.5g) for 10 min at room temperature. Evaporation, addition of water, and isolation with ether afforded N-[2-(2-naphthylthio) ethyl] acetohydroxamic acid (2.49g), m.pt 94-96°C after recrystallization from ethyl acetate.
  • the compound of Example 1 was made up as a 1 mM solution and the cut stem ends of cut carnations were immersed in the resultant solution in order to prolong their freshness.
  • the "Active Ingredient” may be any compound of formula (I') or a physiologically acceptable salt thereof.
  • Example C Cream for Topical Use
  • the methyl and propyl hydroxybenzoates were dissolved in 70ml purified water at 75° and the resulting solution then allowed to cool.
  • the active ingredient was added next and the solution made up to 100ml with purified water.
  • the solution was sterilised by filtration through a membrane filter 0.22 ⁇ pore size and packed aseptically into suitable sterile containers.
  • the active ingredient was dissolved in half of the Water for Injections and then made up to volume and sterilised by filtration. The resulting solution was distributed into ampoules under asceptic conditions.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary 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)

Abstract

Les composés ci-décrits sont représentés par la formule (I), où k est égal à 0 ou à 1; m est égal à 0 et n est égal à 1 ou inversement; Ar représente un groupe phényle ou un groupe naphthyle, l'un et l'autre pouvant être éventuellement substitués par un ou plusieurs substituants choisis entre un groupe alkyle C1-4 (pouvant lui-même être éventuellement substitué par un ou plusieurs atomes halogènes), un groupe alkoxy C1-4, un groupe halo, un groupe nitro, un groupe amino, un groupe carboxy, un groupe alkoxycarbonyle C1-4 et un groupe hydroxy; X représente de l'oxygène ou du soufre; Y est un groupe alkylène C1-6; et R1 et R2 sont choisis de façon indépendante entre un groupe hydrogène et un groupe alkyle C1-4. Des sels desdits composés, destinés à être utilisés dans un procédé de traitement chirurgical, thérapeutique ou diagnostic du corps humain ou du corps animal, présentent des propriétés d'inhibition de lipoxygénases et des cyclooxygénases.
EP19870900230 1985-12-30 1986-12-23 Nouveaux derives aryles Withdrawn EP0250530A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB858531838A GB8531838D0 (en) 1985-12-30 1985-12-30 Aryl derivatives
GB8531838 1985-12-30

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Publication Number Publication Date
EP0250530A1 true EP0250530A1 (fr) 1988-01-07

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EP (1) EP0250530A1 (fr)
JP (1) JPS63502179A (fr)
GB (1) GB8531838D0 (fr)
WO (1) WO1987004152A1 (fr)

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JPS63502179A (ja) 1988-08-25
WO1987004152A1 (fr) 1987-07-16
GB8531838D0 (en) 1986-02-05

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