Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C255/00—Carboxylic acid nitriles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
• • 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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
  • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
  • C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
  • C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring

Definitions

• R is a member selected from the group consisting of hydrogen; halogen; nitro; alkyl having from 1 to carbon atoms; alkoxy having from 1 to 4 carbon atoms; alkenyl having from 2 to 5 carbon atoms; alkynyl having from 2 to 5 carbon atoms; alkylamino having from 1 to 5 carbon atoms; dialkylamino having from 1 to 5 carbon atoms in each alkyl; alkoxyalkyl having from 2 to 6 carbon atoms; alkylaminoalkyl having from 2 to 6 carbon atoms; dialkylaminoalkyl having from 3 to 12 carbon atoms; --(CH ),,CN, (CH ),,NH -(CI-I ,OH, all where x is an integer from O to 3; COOH; -COOR wherein R is an alkyl having from
• R is a member selected from the group consisting of hydrogen, halogen, alkyl having from 1 to 4 carbon atoms, alkoxy having from 1 to 4 carbon atoms, alkanoyl having from 1 to 4 carbon atoms, alkenyl having from 2 to 4 carbon atoms, cyano, amino, nitro, and, together with R 3,4-methylenedioxy;
• R is a member selected from the group consisting of hydrogen and alkyl having from 1 to 3 carbon atoms;
• R is a member selected from the group consisting of alkyl having from 1 to 3 carbon atoms and, together with R -(CH where p is an integer from 4 to 6; and its physiologically compatible acid addition salt.
• Another object of the invention is the development of methods to produce the above l-aryloxy-Z-hydroxy- 3-alkynylamino-propanes.
• a yet further object of the invention is the development of therapeutic compositions and methods with the above l-aryloxy-2-hydroxy-3-alkynylamino-propanes.
• the invention is concerned with novel substituted racemic or optically active l-aryloxy-2-hydroxy-3- alkynylamino-propanes and the acid addition salts thereof, the use of these novel compounds as active ingredients in pharmaceuticals and processes for production thereof.
• novel compounds correspond to general formula wherein, in the formula R is a hydrogen or halogen atom, a nitro group, an alkyl group with l to 5 carbon atoms, an alkoxy group with l to 4 carbon atoms, an alkenyl or alkynyl group with 2 to 5 carbon atoms, a lower alkyl (or di-lower alkyl) amino group, a lower alkoxyalkyl group or a lower alkyl (or di-lower alkyl) amino-lower alkyl group, a group of the partial formula (CI-I --CN, -(CH NI-I or -(CII OI-I, whereby x is zero or an integer from 1 to 3, COOI-I, COOR where R, means an alkyl group of 1 to 4 carbon atoms, an alkenyloxy or alkynyloxy group with 3 to 6 carbon atoms, a lower aliphatic, araliphatic or aromatic acyl-, acyl
• R is a hydrogen or halogen atom, an alkyl or alkoxy group with l to 4 carbon atoms, an acyl or alkenyl group with 2 to 4 carbon atoms, a cyano, amino or nitro group or together with R the 3,4-methylenedioxy group;
• R is hydrogen or an alkyl group with 1 to 3 carbon atoms
• R is an alkyl group with l to 3 carbon atoms or, to-
• R represents a lower aliphatic acyl group
• lower alkanoyl such as the acetyl, propionyl, butyryl or isobutyryl group
• R may, for example, be considered here.
• R may represent phenylalkanoyl, such as the phenacetyl group, which is optionally substituted at the phenyl with one or several halogen atoms, alkyl groups, nitro, cyano or carboxyl groups.
• R represents aromatic acyl, it may be, for example, a benzoyl group optionally substituted once or several times by halogen, lower alkyl, nitro, cyano or carboxyl.
• R represents an acyloxy or acylamino group
• the acyl group therein may as well be represented by the acyl groups individually listed in the above paragraph.
• novel compounds may be produced in a number of ways, in which the following are representative:
• the starting compounds required for carrying outthe processes (a) to (g) have already been partly known. The remainder can be obtained by known processes.
• the epoxides of formula II may be produced easily by reaction with a corresponding phenol or phenolate of formula X where R, to R have the meanings mentioned above and Kt is hydrogen or a cation (e.g., an alkali metal cation).
• the epoxides may be used for production of further starting materials; for instance, the halogen hydrins of formula II may be produced by reacting the epoxides with the corresponding hydrogen halide.
• Amines of formula III have been known and represent mostly commercial products.
• Compounds of formula IV may be obtained by reacting a halohydrin of formula II with a compound (such as vinyl ether or dihydropyran) to give the protective group G and, subsequently, reacting the obtained compound of formula with a compound of general formula III.
• a compound such as vinyl ether or dihydropyran
• the tertiary amines of formula V are obtained by re acting a compound of general formula X with a compound of general formula where R R and Sch have the above-mentioned mean- XIII where R and R have the meanings mentioned above.
• the compounds of formulas VIIa, VIlb, VIII, IXa and IXb already contain the complete l-phenoxy-2- hydroxy-3-alkynylamino-propane structure and may, therefore, be produced analogously to the process (2.) described above, starting from the corresponding phenol, via the corresponding l-phenoxy-2,3-epoxypropane (producible by reaction with epichlorohydrin) by reaction with an alkynylamine of formula III.
• the compounds according to the invention possess an asymmetric carbon atom at the CI-IOH group and can occur, therefore, as racemates as well as in the form of optical antipodes.
• the latter may be obtained by separation of racemates with the conventional optically active acids, such as dibenzoyl- (or di-p-toluyI-)D- tartaric acid or D-3-bromocamphor-8-sulfonic acid or by using optically active starting materials as well.
• l-aryloxy-2-hydroxy-3-alkynylamino-propanes of general formula I according to the invention may be converted into the physiologically compatible acid addition salts thereof in the conventional way.
• Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, methane-sulfonic acid, maleic acid, acetic acid, oxalic acid, lactic acid, tartaric acid or 8- chlorotheophylline.
• the compounds of general formula I or the physiologically compatible acid addition salts thereof have shown valuable therapeutic properties, in particular, adrenolytic properties as demonstrated by animal tests in guinea pigs and may, therefore, be used for treatment or prophylaxis of diseases of the coronaries and for treatment of cardiac arrhythmia, especially of tachycardia, in human medicine.
• the blood-pressure decreasing properties of the compounds are therapeutically interesting too.
• the compounds Compared to the known ,B-receptor blockers, for example, the commercial product 1- 1-naphthyloxy)-2-hydroxy-3-isopropylaminopropane (Propranolol), the compounds have the advantage of a considerably decreased toxicity combined with a superior action.
• the invention therefore, also relates to a process for the treatment of coronary diseases, cardiac arrhythmia and high blood pressure in warm-blooded animals comprising administering a safe but effective amount of the l-aryIoxy-2-hydroxy-3-alkynylamino-propane compounds of formula I.
• R is to be stressed the unsaturated substituents such as alkenyl (e.g., allyl), alkynyl (e. g., ethynyl, propynyl), alkenyloxy (e.g., allyloxy), alkynyloxy (e.g., propargyloxy) or cyano, in particular, if they stand in the 2- position to the propanolamine side-chain.
• alkenyl e.g., allyl
• alkynyl e. ethynyl, propynyl
• alkenyloxy e.g., allyloxy
• alkynyloxy e.g., propargyloxy
• cyano cyano
• R may represent in this case preferably hydrogen, but furthermore, lower alkyl (e.g., methyl), preferably in the 5-position to the propanolamine side-chain, while R is hydrogen as a rule.
• R and R are again preferably methyl.
• a further preferred sub-group is formed by such substances of general formula I, where R represents a hydroxyalkyl, in particular, the hydroxymethyl group; or
• R and R may represent in the first case hydrogen, in the second case hydrogen or else halogen or lower alkyl.
• R, and R are again preferably methyl.
• Important individual compounds are, in particular: l-(2-cyano-phenoxy)-3-(Z-methylbutynyl-3-amino-2)- 2-propanol and l-(2-ethynylphenoxy)-3-(2-methylbutynyl-3-amino-2)-2-propanol, l-(2-allylphenoxy)-3-(2- methylbutynyl-3-amino-2)-2-propanol, furthermore, 1-( 3 ,5-dibromo-4-aminophenoxy)-3-( Z-methylbutynyl-3-amino-2 )-2-propanol l-( 2-hydroxymeth ylphenoxy)-2-(Z-methylbutynyl-3-amino-2)-2-propanol, the l-( 3-chlorophenoxy )-3-( 2-methylbutynyl-3-amino- 2)-2-propanol and the l-(4-acetamidophen
• the single dose of the compounds according to the invention lies at l to 300 mg, preferably 5 to mg (orally) or 1 to 20 mg (parenterally).
• the single dosage is from 0.015 mg to 5 mg/kg.
• the active ingredients according to the invention may be incorporated into the conventional galenic forms of administration, such as tablets, coated tablets, solutions, emulsions, powders, capsules or forms of sustained release.
• the usual pharmaceutical excipients as well as the conventional methods of production may be applied.
• Corresponding tablets may be obtained by mixing the active ingredients with known excipients, for example, with inert diluents, such as calcium carbonate, calcium phosphate or lactose, 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 obtaining sustained release, such as carboxypolymethylene, carboxymethylcellulose, cellulose acetate/phthalate or polyvinylacetate.
• inert diluents such as calcium carbonate, calcium phosphate or lactose
• disintegrants such as corn starch or alginic acid
• binders such as starch or gelatin
• lubricants such as magnesium stearate or talc
• agents for obtaining sustained release such as carboxypolymethylene, carboxymethylcellulose, cellulose acetate/phthalate or polyvinylacetate.
• the tablets may also be composed of several layers. There may be produced correspondingly coated tablets by mans of coating cores, prepared analogous to the tablets, with agents usually applied for tablet-coats, such as polyvinylpyrrolidone or shellac, gum arabic, talc, titanium dioxide or sugar.
• the core may consist of several layers as well.
• the tablet coat for obtaining sustained release may also consist of several layers, whereby the excipients mentioned above for tablets may be used.
• Drinks of the active ingredients or active ingredient combinations according to the invention may additionally contain a sweetener, such as saccharin, cyclamate, glycerin or sugar, as well as an agent improving the taste, for example, a flavor, such as vanilla or orange extract.
• a sweetener such as saccharin, cyclamate, glycerin or sugar
• an agent improving the taste for example, a flavor, such as vanilla or orange extract.
• a sweetener such as saccharin, cyclamate, glycerin or sugar
• an agent improving the taste for example, a flavor, such as vanilla or orange extract.
• a sweetener such as saccharin, cyclamate, glycerin or sugar
• an agent improving the taste for example, a flavor, such as vanilla or orange extract.
• a flavor such as vanilla or orange extract
• suspension auxiliaries or thickeners such as sodium carboxymethylcellulose, wetting agents, such as condensation products of fatty alcohols with ethylene oxide, or protective substances,
• Injectable solutions are produced in the conventional way, such as under addition of preservation agents, such as p-hydroxybenzoates, or stabilizers, such as Komplexonen (the sodium salt of ethylene diaminetetraacetic acid), and filled into injection vials or ampoules.
• preservation agents such as p-hydroxybenzoates, or stabilizers, such as Komplexonen (the sodium salt of ethylene diaminetetraacetic acid)
• Komplexonen the sodium salt of ethylene diaminetetraacetic acid
• Capsules containing the active ingredients or active ingredient combinations may be produced, for example, by admixing the active ingredients with inert carri- EXAMPLE 1 l-a-Naphthoxy-3-( 3-ethylpentynyl-4-amino-3 )-2- propanol HCl (according to process [a]) (I, R H,
• EXAMPLE 2 1-m-To1yloxy-3-(2-methy1butynyl-3-amino-2)-2- propanol HCl (according to process [a]) (1, R 3-CH R and R H, R, and R CH 8.2 Grams (0.05 mol) of l-m-tolyloxy-2,3-epoxypropane were dissolved in 90 ml of ethanol, and after addition of 6.25 gm (0.075 mol) of 2-methyl-2- aminebutyne-3, the mixture was refluxed for two hours. After distilling off the solvent, the residue was recrystallized from ethyl acetate under addition of petroleum ether.
• the crystalline base was dissolved in acetonitrile; alcoholic HCl was added and crystallization was started under addition of ether. 6.5 Grams of colorless crystals were obtained, which are chromatographically pure. M.p. 139 to 141C.
• the precipitating base was dissolved in chloroform and the organic phase, after separation, was dried over Na SO After filtration the chloroform was distilled off and the residue wass recrystallized from ethyl acetate under addition of petroleum ether.
• the base was dissolved in acetonitrile and acidified with alcoholic HCl. The hydrochloride crystallized colorlessly.
• EXAMPLE 8 l-( 2-Cyanophenoxy )-3-( Z-methylbutyn e-3-amino-2 2-propanol HCl (according to process [d]) (I, R, 2-CN, R and R H, R; and R CH 2.84 Grams (0.01 mol) of 3-(2-methylbutyne-3-yl- 2)-5-(2-cyanophenoxymethyl)-oxazolidine-2-one were refluxed in 20 ml of ethanol, after addition of 3 gm of KOH in 6 ml of water, for three hours. After having distilled off the solvent, the residue was treated with water and extracted with chloroform.
• EXAMPLE 9 1-( 4-Amino phenoxy )-3-( 2-methylbutynyl-3-amino-2 2-propanol HCl (according to process [e]) (1, R 4-NH R and R H, R and R CH A mixture of 8.1 gm of tin-I1 chloride in 20 ml of conc. HCl was heated to 60C and 2.62 gm (0.01 mol) of l-( 4-nitrophenoxy 3 2-methylbutynyl-3-amino- 2)-2-propanol were added in portions, so that the temperature did not exceed 65C. After the addition had been finished, the mixture was stirredfor 30 minutes and after cooling off it was adjusted alkaline with NaOH.
• the compound 1-(4- hydroxyphenoxy)-3(2-methylbutynyl-3-amino-2)-2- propanol was made by heating the compound l-(4-diethylaminocarbonyloxyphenoxy)-3-(2-methylbutynyl-3- amino-2)-2-propanol (m.p. of hydrochloride: 126C) in the presence of concentrated aqueous HCl.
• M.p. of the end product (base) is 136 to 137.5C.
• EXAMPLE l3 1-( 3,5-Dibromo-4-aminophenoxy)-3-( 2-methylbutynyl-3-amino-2)-2-propanol 2 RC1 (according to R and R CH 4.96 Grams (0.02 mol) of l-(4-aminophenoxy)-3-(2- methylbutynyl-3-amino-2)-2-propano1 were added into a mixture of 30 ml of HBr (65%) and 10 ml of water and heated to 45C. While stirring and cooling, 4.54 gm (0.04 mol) of H 0 30%, were dropped into the mixture in such a way that the temperature did not rise over 65C.
• the crystalline substance was vacuum filtered after cooling. It was then recrystallized from ethanol under addition of ether. Then the hydrochloride was dissolved in water. NaOH was added. The base was extracted with CHClg and, after evaporation of the solvent, recrystallized from ethyl acetate under addition of petroleum ether. The chromatographically pure base was dissolved in ethanol; alcoholic HCl was added and the dihydrochloride was brought to crystallization under addition of ether. Yield: 3.8 gm, m.p. 183 to 185C.
• the substances l-( 2-cyanophenoxy)-3-( lethynylcyclohexylamino)-2-propanol. HCl and 1-(2- cyano-4-chlorophenoxy)-3-( 2-methylbutynyl-3-amino- 2)-2-propanol may be used in the same quantity.
• PRODUCTION Active ingredient, CMC and stearic acid were mixed well and the mixture was granulated in the usual way, using a solution of the CAP in 200 ml of a mixture of ethanol/ethyl acetate. Then the granulate was pressed to 380 mg cores, coated in the conventional way with a sugary 5% solution of polyvinylpyrrolidone in water. Each coated tablet contains 25 mg of active ingredient.
• the active ingredient together with the lactose, corn starch, colloidal silicic acid and polyvinyl pyrrolidone was granulated after thorough mixing in the usual way, using an aqueous solution of the soluble starch.
• the granulate was admixed with the magnesium stearate and pressed into 1000 tablets each of 500 mg of weight, containing each 35 mg of the first and mg of the second active ingredient.
• R is (CH -CN, where X is O, 1, 2 or 3, R is hydrogen, halogen or NHCONI-IR, where R is lower alkyl, and R and R are methyl, or a physiologically compatible acid addition salt thereof.
• a compound of claim 1, which is of the formula 18 R is hydrogen, chlorine or NHCONHR,
• R is alkyl of l to 3 carbon atoms, and R and R are methyl. or a physiologically compatible acid addition salt 5 thereof.
• a compound of claim 3 which is of the formula wherein R is hydrogen, chlorine or NH-CONHR, CHZ 2 H where R is alkyl of l to 3 carbon atoms, and H3 R and R are methyl, ethyl or together pentamethylene or a h slolo icall com atible acid addition salt or a physiologically compatible acid addition salt thereog y g y p thereofi 6.
• R is 2-cyano, R
• a compound of claim 3 is hydrogen and R and R are methyl.

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• 1974
  • 1974-02-11 AT AT104774A patent/AT330150B/de not_active IP Right Cessation
  • 1974-02-21 ES ES423466A patent/ES423466A1/es not_active Expired
  • 1974-02-22 US US444713A patent/US3925446A/en not_active Expired - Lifetime
  • 1974-02-25 FI FI544/74A patent/FI62054C/fi active
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  • 1974-02-26 BG BG26941A patent/BG20335A3/xx unknown
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  • 1974-02-27 CH CH1485477A patent/CH605637A5/xx not_active IP Right Cessation
  • 1974-02-27 CH CH1485577A patent/CH605638A5/xx not_active IP Right Cessation
  • 1974-02-27 MX MX745489U patent/MX4588E/es unknown
  • 1974-02-27 CA CA193,683A patent/CA1062717A/en not_active Expired
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  • 1974-02-28 FR FR7406835A patent/FR2218900B1/fr not_active Expired
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  • 1974-08-27 CH CH1485877A patent/CH605639A5/xx not_active IP Right Cessation
• 1975
  • 1975-01-29 SU SU752100046A patent/SU793381A3/ru active
  • 1975-04-04 ES ES436313A patent/ES436313A1/es not_active Expired
  • 1975-04-04 ES ES436315A patent/ES436315A1/es not_active Expired
  • 1975-04-04 ES ES436311A patent/ES436311A1/es not_active Expired
  • 1975-04-04 ES ES436312A patent/ES436312A1/es not_active Expired
  • 1975-04-04 ES ES436314A patent/ES436314A1/es not_active Expired
  • 1975-04-04 ES ES436316A patent/ES436316A1/es not_active Expired
• 1980
  • 1980-04-22 YU YU01095/80A patent/YU109580A/xx unknown

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