Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
  • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
  • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
  • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
  • C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
  • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
  • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

• each of R and R is a member chosen from the group consisting of hydrogen, chlorine, bromine, iodine, alkyl and alkoxy each having up to six carbon atoms; each of R and R is a member chosen from the group consisting of hydrogen and alkyl containing up to six carbon atoms;
• X is a member chosen from the group consisting of (CH CH NH and CH CH NH wherein n is an integer of from one to six; and each of R and R is a member chosen from the group consisting of hydrogen, alkyl containing up to six carbon atoms, acyl containing from two to six carbon atoms, and when taken together with the nitrogen atoms to which they are attached, form part of a heterocyclic ring.
• each of R and R is a member chosen from the group consisting of hydrogen, chlorine, bromine, lower alkyl and lower alkoxy;
• X is a member chosen from the group consisting of lower alkylene, CH NH and CH CH NH;
• R is a member chosen from the group consisting of hydrogen and lower alkyl; and each of R and R are members chosen from the group consisting of hydrogen and lower alkyl and, when taken together with the nitrogen atoms to which they are attached and the carbon atom which is geminal to said nitrogen atoms, imidazolyl.
• Typical member compounds of this series include such Z-guanidinoalkyl 1,4 benzodioxanes as 2 guanidinomethyl 1,4 benzodioxane, Z-guanidinomethyl-6,7-dichloro 1,4 benzodioxane, 2-(3-guanidinopropyl)-1,4- benzodioxane, 2 guanidinoaminomethyl-l,4-benzodioxane, 2-(l-methylguanidino)methyl-1,4-benzodioxane, 2- (N,N ethyleneguanidinomethyl)-1,4-benzodioxane, and the like.
• the process employed for preparing the novel compounds of this invention involves treating an appropriately substituted 2-aminoalkyl-1,4-benzodioxane compound with a suitable S-alkyl isothiouronium salt having the requisite substituent groups.
• This particular reaction is 3,247,221 Patented Apr. 19, 1966 normally carried out in a reaction-inert polar solvent medium at a temperature ranging from about 20 C. up to about C. for a period of about one to about 72 hours.
• the desired S-allyl isothiouronium salt reagent is preferably one where the S-alkyl group is lower alkyl in view of relative ease with which such a reaction takes place due to the more volatile nature of the by-products produced, i.e., the lower boiling mercaptans.
• Preferred reaction-inert polar solvents for use in this connection include water, lower alkanols, such as methanol, ethanol and isopropanol, etc., and N,N-di(lower alkyl)alkanoamides such as N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, N,N-diethylacetamide, N,N di(n propyl)fo'rmamide, N,N-dimethylpropionamide, and so forth, as well as mixtures of either of these two aforementioned type organic solvents with water.
• lower alkanols such as methanol, ethanol and isopropanol, etc.
• N,N-di(lower alkyl)alkanoamides such as N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, N,N-diethylacetamide, N,N
• the solvent is removed by means of conventional procedures and the resulting residue taken up in a suitable solvent system, such as one of the aforementioned types, from which it can be subsequently crystallized.
• a suitable solvent system such as one of the aforementioned types, from which it can be subsequently crystallized.
• the product may separate first from the reaction mixture either during the course of the reaction or immediately therefater, or it may be crystallized from the reaction solution after some initial concentration of same.
• a final conversion to the desired organic base compound can then be effected by treating the Z-guanidinoalkyl-1,4-benzodioxane acid addition salt thus obtained with suflicient base in water to neutralize same, e.g., an alkaline reagent such as sodium hydroxide in water can be used.
• Recovery of the desired free organic base can then be had by extracting the aforesaid aqueous solution with a suitable water-immiscible organic solvent of low volatility, such as a halogenated aliphatic hydrocarbon solvent like methylene chloride, for example.
• a suitable water-immiscible organic solvent of low volatility such as a halogenated aliphatic hydrocarbon solvent like methylene chloride, for example.
• the starting materials necessary for the above reaction process are either all known compounds or else they are easily prepared by those skilled in the art in accordance with standard organic procedures.
• the 2- aminoalkyl-l,4-benzodioxanes can easily be prepared by known routes starting from the corresponding 2-haloalkyl-1,4-benzodioxanes, which are, in turn, prepared via ring-closure of the appropriate catechol compounds with reagents such as epichlorohydrin, etc.
• the corresponding S-alkyl isothiouronium salts, such as S-methyl isothiouronium sulfate, and so on, are, of course, members of a well-known class of organic compounds.
• the most preferred one is the first mentioned process involving the reaction of a 2- sulfonyloxyalkyl-1,4-benzodioxane, such as 2-(p-toluene sulfonyloxy)methyl-1,4-benzodioxane, with a guanidine salt such as the hydrochloride to form the corresponding Z-guanidinoalkyl-l,4-benzodioxane sulfonate salt direct.
• This process is generally carried out by heating the two reactants together in an alcoholic solvent medium (usually, at steam bath temperatures) in the presence of a basic condensing agent like sodium hydride, for example. Recovery of the desired product from the reaction mixture is then easily effected by means of evaporation under reduced pressure, followed by subsequent crystallization of the resulting residue from water.
• the Z-guanidinoalkyl-l,4-benzodioxane compounds of this invention are basic compounds, they are capable of forming a wide variety of salts with various mineral and organic acids. Although such salts must be pharmaceutically acceptable when the final products are intended for oral consumption, it is possible to first isolate the desired Z-guanidinoalkyl-l,4-benzodioxane compound from the reaction mixture as a pharmacetuically unacceptable salt and then to subsequently convert the latter, as indicated previously, to the free base by treatment with an alkaline reagent, followed by the final conversion to the pharmaceutically acceptable acid salt in the manner hereinafter indicated.
• the acid addition salts of the 2 guanidinoalkyl 1,4 benzodioxane compounds of this invention may be prepared by treating the base compound with a substantially equimolar amount of the chosen acid.
• the salt-formation step can be carried out in an aqueous solution or in a suitable organic solvent such as methanol or ethanol. Upon careful evaporation of the solvent, the solid salt is obtained.
• the acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned Z-guanidinoalkyl-1,4-benzodioxane bases of this invention are those which form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate, or acid citrate, tartrate or bitartrate, oxalate, succinate, maleate, gluconate, methanesulfonate, ethanesulfonate, benzenesulfonate and p-toluenesulfonate salts.
• pharmaceutically acceptable anions such as the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate
• the compounds of the present invention are all readily adapted to therapeutic use as antihypertensive agents in view of their ability to lower the blood pressure of correspondingly agitated subjects.
• Z-guanidinomethyl-l,4-benzodioxane has been found to produce a definite antihypertensive effect in man by lowering the blood pressure of hypertensive patients to a statistically significant degree when orally administered to them.
• this particular compound produces its antihypertensive effect in man in both the lying and standing positions, although the effect is more pronounced when the patient is standing.
• no problems of toxicity or any other untoward side effects have been encountered in the administration of these compounds.
• the herein described antihypertensives can be administered to an agitated subject via the oral or parenteral routes.
• these compounds are most desirably administered in doses ranging from about 10 mg. up to about 240 mg. per day, although variations will necessarily occur depending upon the weight of the subject being treated and the particular route of administration chosen.
• a dosage level that is in the range of from about 0.15 mg. to about 4.8 mg. per kg. of body weight per day is most desirably employed in order to achieve eifective results.
• dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger dosages may be employed without causing any harmful or deleterious side effects to occur provided that such higher dose levels are first divided into several smaller doses that are to be administered throughout the day.
• the 2-guanidinoalkyl-l,4- benzodioxane compounds of this invention may be administered either alone or in combination with pharmaceutically acceptable carriers by either of the routes previously indicated, and that such administration can be carried out in both single and multiple dosages.
• the novel compounds of this invention can be administered in a Wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, aqueous suspensions, injectable solution, elixirs, syrups, and the like.
• Such carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc.
• oral pharmaceutical compositions can be suitably sweetened and/or flavored by means of various agents of the type commonly employed for just such a purpose.
• the therapeutically-etfective compounds of this invention are present in such dosage forms at concentration levels ranging from about 0.5% to about by weight of the total composition, i.e., in amounts which are sufficient to provide the desired unit dosage previously indicated.
• tablets containing various excipients such as sodium citrate, calcium carbonate and dicalcium phosphate may be employed along with various disintegrants such as starch and preferably potato or tapioca starch, alginic acid and certain complex silicates, together with binding agents such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such a magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes.
• Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules; preferred materials in this connection would also include lactose or milk sugar as well as high molecular weight polyethylene glycols.
• the essential active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and/or suspending agents, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.
• solutions of these particular 2 guanidinoalkyl 1,4 benzodioxanes in sesame or peanut oil or in aqueous-propylene glycol or N,N-dimethylformamide may be employed, as well as sterile aqueous solutions of the corresponding water-soluble, non-toxic mineral and organic acid addition salts previously enumerated.
• aqueous solutions should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose.
• These particular aqueous solutions are especially suitable for intravenous, intramuscular and intraperitoneal injection purposes.
• the sterile aqueous media employed are readily obtained by standard techniques well-known to those in the art.
• distilled water is ordinarily used as the liquid diluent and the final preparation is passed through a suitable bacterial filter, such as a sintered-glass filter or a diatomaceous-earth or unglazed porcelain filter.
• Preferred filters of this type include the Berkefeld, the Chamberland and the asbestos disc-metal S'eitz filter, wherein the fluid is sucked through the filter candle into a sterile container with the aid of a suction pump.
• the necessary steps should be taken throughout the preparation of these injectable solutions to ensure that the final products are obtained in a sterile condition.
• Example I Three and one-third parts by weight of Z-aminomethyl- 1,4-benzodioxane and 278- parts by weight of S-methyl isothiouronium sulfate were dissolved in 20 parts by volume of water, and the resulting aqueous solution was heated under reflux for three hours. At the end of this time, the solvent was removed by means of evaporation under reduced pressure and the residue so obtained dissolved in a minimum amount of fresh water and treated with charcoal. Upon filtration, there was obtained a clear filtrate which, on standing, soon afforded pure crystals of di(2-guanidinomethyl-1,4-benzodioxane) sulfate, M.P. 204-205 C.
• Example II Three and two-tenths parts by weight of Z-aminoethyl- 1,4-benzodioxane and 2.5 parts by weight of S-methyl isothiouronium sulfate were dissolved in ml. of water, and the resulting aqueous solution was heated under reflux for four hours. Upon cooling, the solid material which had started to separate during the course of the reaction was removed by means of suction filtration and recrystallized once from aqueous ethanol and then from water. In this manner, there was obtain di[2-(2-guanidinoethyl)-1,4-benzodioxane] sulfate, M.P. 250252 C.
• Example III A mixture consisting of 3.0 parts by Weight of 2-(3- aminopropyl)-1,4-benzodioxane, 2.2 parts by weight of S-rnethyl isothiouronium sulfate, and 10 parts by volume of ethanol together with 10 parts by volume of water, was heated on a steam bath for six hours. On standing at room temperature (-25" C.) overnight, i.e., for about 16 hours, the product soon crystallized. It was subsequently removed by means of filtration, crystallized from aqueous ethanol once and then from water twice to give 1.9 parts by weight of pure di[2-(3-guanidinopropyl)- 1,4-benzodioxane] sulfate, M.P. 202-205 C. (decomp).
• Example IV Nine parts by weight of 2-aminomethyl-6,7-dichloro- 1,4-benzodioxane and 5.35 parts by weight of S-methyl isothiouronium sulfate in 30 ml. of aqueous ethanol formed a solution which was subsequently heated under reflux for six hours. Upon cooling, the solid material which had separated during the course of the reaction was removed by means of suction filtration and thereafter twice recrystallized from glacial acetic acid and, finally, from water. In this manner, there was obtained di(2- guanidinomethyl 6,7-dichloro-1,4-benzodioxane) sulfate, M.P. 281283 C.
• Example V A mixture consisting of 5.0 parts by weight of 2-aminomethyl-6(7)-methyl-1,4-benzodioxane and 3.8 parts by weight of S-methyl isothiouronium sulfate in 10 parts by volume of water was made homogenous by the addition of ethanol and thereafter heated on a steam bath for four hours. The resulting solution was then evaporated under reduced pressure on a steam bath and the residue so obtained dried by azeotropic distillation with toluene, followed by extraction with aqueous ethanol. The ethanolic extract was then concentrated in vacuo and the resulting crystalline material once recrystallized from ethanol, once from aqueous ethanol and then twice from water. In this manner, there were obtained 1.3 parts by weight of di(Z-guanidinor'nethyl 6(7)-methyl-1,4-benzodioxane) sulfate, M.P. 215-218 C.
• Example VI A mixture consisting of 15 parts by weight of 2-aminomethyl 5(8) methyl 1,4 benzodi'oxane, 11.6 parts by weight of S-methyl isothiouronium sulfate, 20.20 parts by volume of water and suflicient ethanol to render the mixture homogenous was heated on a steam bath for five hours. The Water was then removed from the reaction mixture by means of azeotropic distillation with toluene, and the resulting residual solid was crystallized once from aqueous ethanol and then twice recrystallized from water. In this manner, there were obtained three parts by weight of di(2 guanidinomethyl-S (8)-methyl-l,4-benzodioxane) sulfate, M.P. 260262 C. (decomp);
• Example VII A solution consisting of 3.0 parts by weight of 2-aminomethyl-5(8)-isopropyl-1,4-benzodioxane and 2.0 parts by weight of S-methyl isothiouronium sulfate in 15 parts by volume of water with sufficient ethanol to make the mixture homogeneous was refluxed for six hours. The solvent was then removed in vacuo on a steam bath, and the resulting product dried by means of azeotropic distillation with toluene. The syrup which resulted was eventually partially solidified after prolonged tritur ation with diethyl ether. Recrystallization from water then gave 0.1 part by weight of di(2-guanidinornethyl-5(8)- isopropyl-l,4-benzodioxane) sulfate, M.P. C.
• Example VIII A mixture of one part by weight of 2-aminomethyl-7- chloro-1,4-benzodioxane and 0.7 part by weight of S- methyl isothiouronium sulfate in aqueous ethanol was heated for 24 hours. The mixture was subsequently evaporated on a steam bath in vacuo and dried by azeotropic distillation with toluene. The syrup which resulted was then boiled in water with charcoal, filtered and cooled to room temperature. On standing, there was obtained 0.12 part by weight of di(2-guanidinomethyl-7-cloro-1,4- benzodioxane) sulfate, M.P. 222-224 C.
• Example IX A mixture consisting of 4.8 parts by weight of Z-aminomethyl-(8)-methoxy-1,4-benzodioxane and 3.24 parts by weight of S-methyl isothiouronium sulfate in aqueous ethanol was heated for six hours on a steam bath. The solvent was then removed by means of evaporation under reduced pressure on a steam bath and ethanol was added to the residual oil which eventually solidified. The sticky solid thus obtained was washed twice with boiling ethanol, and then recrystallized twice from aqueous ethanol and once from water. In this manner, there was obtained 0.18 part by weight of di(2-guanidinomethyl-5(8)-methoxy-l,4-benzodioxane) sulfate, M.P. 278-283 C.
• Example X Ten and nine-tenths parts by weight of 2-aminomethyl- 7-methoxy-1,4-benzodioxane in parts by weight of ethanol were heated on a steam bath for 10 hours with 7.78 parts by weight of S-methyl isothiouronium sulfate in 40 parts by volume of water. Upon completion of this step, the resulting aqueous solution was heated with charcoal and then filtered. The filtrate thus obtained deposited a gum on cooling and the latter material eventually solidified. This solid was then recrystallized from water six times and there were obtained 2.32 parts by weight of di(2-"uanidinomethyl-7-methoxy-1,4-benzodioxane) sulfate, M.P. 224-227 C.
• Example XI Nine parts by weight of Z-hydrazinomethyl-1,4-benzedioxane and 7.0 parts by Weight of S-methyl isothiouronium sulfate were refluxed together in 25 ml. of water for 1.5 hours. Upon completion of this step, an oil soon precipitated from the reaction mixture while standing at room temperature (-25 C.). This oil eventually crystallized and after several recrystallizations from water, there was obtained di(2-guanidinoaminomethyl-1,4-hemlodioxane) sulfate, M.P. l93195 C.
• Example XII Six and six-tenths parts by weight of 2-aminomethyl 1,4-benzodioxane and 9.28 parts by weight of N,S-dimethyl isothiouronium hydriodide in 15 ml. of aqueous dimethylformamide were heated on a steam bath for six hours. The solvent was then removed from the reaction mixture by means of distillation and the residual material basiiied with 10 N sodium hydroxide solution. Upon extraction of the resulting mixture with chloroform followed by a three-fold extraction of the chloroform extract with dilute hydrochloric acid, there was obtained a slightly acidic aqueous solution which was subsequently basified by the addition of excess solid sodium hydroxide.
• the basified aqueous solution was then extracted with chloroform, and the latter extract subsequently dried over anhydrous magnesium sulfate and filtered.
• the solvent was then removed from the resulting filtrate by means of distillation and the residue thus obtained was subsequently dissolved in methanol, and thereafter added to a solution of excess l-di-(p-toluoyl)-D-tartaric acid in methanol.
• Example XIII Three and one-third parts by weight of 2-aminomethyl- 1,4-benzodioxane and 4.92 parts by weight of N,N',S-trimethyl isothiouronium hydriodide in 10 ml. of aqueous dimethylformamide were warmed together on a steam bath for six hours. The solvent was then removed from the reaction mixture by means of distillation, and the residual oil basified with 10 N sodium hydroxide solution. The resulting aqueous solution was then extracted with diethylether, and the ether extract thus obtained was subsequently dried over anhydrous magnesium sulfate.
• Example XIV 2-(N-methyl)-aminomethyl 1,4-benzodioxane (5.37 parts by weight) and S-methyl isothiouronium sulfate (4.18 parts by weight) in 20 ml. of aqueous ethanol were refluxed together for 48 hours. The solvent was then removed by means of distillation under reduced pressure, and the residue so obtained was crystallized from ethanol and then from water. In this manner, there was obtained di[2-(l-methylguanidino)methyl-1,4- benzodioxane] sulfate, M.P. 271272 C. (decomp.).
• Example XV 2-aminomethyl 1,4 benzodioxane (4.13 parts by weight) and S-methyl N,N-ethyleneisothiouronium hydriodide (6.1 parts by weight) in 25 ml. of absolute ethanol were refluxed together for six hours. The solvent was then removed by means of distillation under reduced pressure, and the residual oil which resulted was dissolved in a small amount of ethanol and basified with 10 N sodium hydroxide solution. The resulting aqueous solution was then extracted with diethylether and the ether extracts subsequently dried over anhydrous potassium carbonate and filtered.
• Example XVI Ten parts by weight of di(Z-guanidinomethyl-l,4- benzodioxane) sulfate in parts by volume of water is neutralized with 10 N sodium hydroxide solution. Extraction of the resulting aqueous solution with several portions of methylene chloride, followed by separation of the organic layer and its subsequent concentration under reduced pressure then affords Z-guanidinomethyl-1,4-benzodioxane as a free base.
• Example XVII The following 2-guanidinoalkyl-l,4 benzodioxanes can 10 was treated with 8.1 g. (0.085 mole) of guanidine hydrochloride in one portion. The mixture was then stirred and refluxed on a steam bath for 30 minutes, filtered While still hot and added to a refluxing solution be Prepared according to the procedure of the previous 5 ,3 2' 3. f g i i' examples from the appropriate starting compounds: e nzo-loxane Isuo W m 0 utcno The reaction mixture was then stirred and refluxed for seven hours, after which time it was evaporated to dry- NR ness under reduced pressure. Upon extraction of the I 1O residue with threeml.
• Example XIX m The nitrate, sulfate or ⁇ bisulfate (other than those pre- 0 viously recorded (phosphate or acid phosphate, acetate, R2 e lactate, citrate or acid citrate, tartrate or bitartrate, oxalate, succinate, maleate, gluconate, saccharate, methaneand the pharmaceutically acceptable acid addition salts sulfonate, ethanesulfonate, benzenesulfonate and p-tolthereof wherein each of R and R is selected from the uenesulfonate salts of each of the 2-guanidinoalkyl-l,4- group consisting of hydrogen, chlorine, bromine, lower benzodioxane bases previously reported in Examples alkyl and lower alkoxy; X is selected from the group XVL-XVII are all prepared by separately dissolving in consisting of lower alkylene, CH NH and a suitable amount of ethanol
• Example XX A solution of 3.8 g. (0.08 mole) of sodium hydride (50% dispersion in oil) in tert.-butanol (sodium-dried) No references cited.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Plural Heterocyclic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=10133350

Family Applications (1)

Country Status (11)

Cited By (13)

• 0
  • GB GB1030752D patent/GB1030752A/en active Active
  • BE BE632701D patent/BE632701A/xx unknown
• 1963
  • 1963-05-16 US US281048A patent/US3247221A/en not_active Expired - Lifetime
  • 1963-05-18 DE DE19631518088 patent/DE1518088A1/de not_active Withdrawn
  • 1963-05-21 DK DK177465AA patent/DK107355C/da active
  • 1963-05-21 DK DK241663AA patent/DK107354C/da active
  • 1963-05-21 ES ES288219A patent/ES288219A1/es not_active Expired
  • 1963-05-21 BR BR149262/63A patent/BR6349262D0/pt unknown
  • 1963-05-22 FR FR935737A patent/FR3085M/fr active Active
  • 1963-05-22 AT AT416463A patent/AT251599B/de active
  • 1963-05-22 SE SE5695/63A patent/SE310498B/xx unknown
  • 1963-05-22 CH CH641863A patent/CH446389A/de unknown

Non-Patent Citations (1)

Also Published As

Similar Documents