US3359263A - Nu-substituted-1-phenyl-2-aminopropanes - Google Patents

Nu-substituted-1-phenyl-2-aminopropanes Download PDF

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US3359263A
US3359263A US302707A US30270763A US3359263A US 3359263 A US3359263 A US 3359263A US 302707 A US302707 A US 302707A US 30270763 A US30270763 A US 30270763A US 3359263 A US3359263 A US 3359263A
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phenyl
dibenzo
dihydro
ylidene
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Stelt Cornelis Van Der
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Koninklijke Pharmaceutische Fabrieken NV
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
    • C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/90—Xanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • R is lower alkyl (e.g., methyl, ethyl); R is selected from the group consisting of hydrogen, halogen (e.g., chloro, bromo, fluoro) and lower alkyl (e.
  • novel compounds of this invention are physiologically useful and possess coronary blood vessel dilating activity and may be employed in treatment of such conditions as coronary disease, the dosage being adjusted to the patients needs and the relative potency of the compound employed.
  • the invention includes within its scope pharmaceutical preparations containing one or more of the therapeutically active compounds of this invention, or non-toxic acid addition salts thereof, in association with a pharmacologically acceptable carrier.
  • the preparation may take any of the forms customarily employed for administration of therapeutically active substances but the preferred types are those suitable for oral administration and especially tablets, pills, and capsules including the substance.
  • the tablets and pills may be formulated in manner, known per se with one or more pharmacologically acceptable diluents or excipients such as lactose or starch, and include materials of a lubricating nature such as calcium stearate.
  • Capsules made of absorbable material may contain the active substance alone or in admixture with a.solid or liquid diluent.
  • Liquid preparations may be in the form of suspensions, emulsions, syrups or elixirs of the active substance in water or other liquid medium commonly used for making orally acceptable pharmaceutical formulations, such as liquid paralfin, or a syrup or elixir base.
  • the active substance may also be made up in a form suitable for parenteral administration, i.e., as a suspension or emulsion in sterile water or an organic liquid usually employed for injectable preparations, for example vegetable oil such as olive oil, or a sterile solution in an organic solvent.
  • the compounds of this invention may be employed directly or in the form of their physiologically acceptable non-toxic acid addition salts, i.e., salts which are not harmful to the animal organism when used in therapeutic doses, derived from inorganic acids such .as the hydrohalic acids, for example, hydrochloric or hydrobromic acid, and from organic acids, such as citric maleic, fumaric, tartaric and succinic acids.
  • physiologically acceptable non-toxic acid addition salts i.e., salts which are not harmful to the animal organism when used in therapeutic doses, derived from inorganic acids such .as the hydrohalic acids, for example, hydrochloric or hydrobromic acid, and from organic acids, such as citric maleic, fumaric, tartaric and succinic acids.
  • the preferred compounds of this invention are those wherein R is hydrogen, Y is lower alkylene (e.g., ethylene) when n is 1, and Z is CH CH.
  • the most preferable compounds of this invention are N-[2-(l(l,l1-dihydro-SH-dibenzo [a,d] cyclohepten-S-yDethyl]-l-phenyl-2- aminopropane and N-[2-(fiuoren-9-ylidene)ethy1]-1-phenyI-Z-aminoprop-ane and the pharmaceutically acceptable nontoxic acid addition salts thereof.
  • the compounds of this invention may be prepared according to the processes of this invention, by first reacting a 1-phenyl-aminoalkane, for example, dl-l-phenyl- Z-aminopropane or dl-l-phenyl-Z-aminobutane, with an aldehyde of the general formulawherein Y, n and R are as hereinbefore defined to yield a compound of the formula wherein R, R, Y and n are as hereinbefore defined.
  • a 1-phenyl-aminoalkane for example, dl-l-phenyl- Z-aminopropane or dl-l-phenyl-Z-aminobutane
  • R, R, Y and n are as hereinbefore defined.
  • the aldehydes employed as starting materials may be prepared by condensing a ketone of the formula wherein R, Y and n are as hereinbefore defined, under the influence of a condensing agent such 'as sodamide with acetylene in a medium of liquid ammonia to yield an acetylenic compound of the formula HCEC and causing isomerization of the acetylenic compound by treatment with acid to give aldehydes of the general formula set forth hereinabove.
  • Acid addition salts of the compounds of this invention may be prepared by methods known per se.
  • the base may be treated with the equivalent quantity of the acid in an inert solvent such as diethyl ether.
  • a one litre flask is fitted with a dropping-funnel, a gas-inlet tube filled with solid potassium hydroxide, and a condenser to the upper end of which a tube filled with solid potassium hydroxide is attached. Flask and condenser are cooled with solid carbon dioxide in acetone. From a gas cylinder a quantity of about 200-250 ml. of ammonia is condensed into the flask through the tube filled with potassium hydroxide. Another flask, fitted with an inlet tube nearly reaching to the bottom, an outlet tube and an ascending tube is filled with water.
  • the inlet tube is connected with two washing-bottles placed in series and filled with concentrated sulphuric acid and, moreover, with a tower filled with glass-wool.
  • the latter system is connected with a supply of nitrogen gas.
  • the air is completely replaced by nitrogen by bubbling same through the system.
  • the nitrogen supply is switched off and a stream of acetylene gas passed through the flask containing water to remove acetone vapor stemming from the acetone soaked diatom aceous earth, wherein the acetylene is dissolved in the cylinder.
  • the outlet of the tower is then connected with the inlet tube of the flask, containing the liquid ammonia. 0.2 g.
  • the 9-l'luorenylidene acetaldehyde used as a starting material can be prepared from fluorenone in the following way.
  • R is lower alkyl
  • R is selected from the group consisting of hydrogen, halogen, and lower alkyl
  • Y is selected from the group consisting of oxygen and sulfur

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)

Description

United States Patent 3,359,263 N-SUBSTITUTED-l-PHENYL-2-AM1NOPROPANES Cornelis van der Stelt, Haarlem, Netherlands, assiguor to N .V. Koninklijke Pharmaceutische Fabrieken v/ h Brocades Stheeman en Pharmacia, Amsterdam, Netherlands, a corporation of Dutch law No Drawing. Filed Aug. 16, 1963, Ser. No. 302,707 Claims priority, application Great Britain, Oct. 19, 1962, 39,753/62 3 Claims. (Cl. 260-240) This invention relates to the provision of new physiologically active compounds and more particularly to N- substituted-l-phenyl-Z-aminopropanes, processes for their production and to novel pharmaceutical compositions containing them.
The compounds of this invention may be represented by the formula CYn wherein R is lower alkyl (e.g., methyl, ethyl); R is selected from the group consisting of hydrogen, halogen (e.g., chloro, bromo, fluoro) and lower alkyl (e.g., methyl, ethyl, propyl, iso-propyl, butyl); n is selected from the group consisting of 0 and 1; Y is selected from the group consisting of lower alkylene (e.g., methylene, ethylene, propylene), alkenylene (e.g., ethenylene, propenylene), oxygen and sulfur; and Z is selected from the group consisting of CH CH and CH=C.
The novel compounds of this invention are physiologically useful and possess coronary blood vessel dilating activity and may be employed in treatment of such conditions as coronary disease, the dosage being adjusted to the patients needs and the relative potency of the compound employed.
The invention includes within its scope pharmaceutical preparations containing one or more of the therapeutically active compounds of this invention, or non-toxic acid addition salts thereof, in association with a pharmacologically acceptable carrier. The preparation may take any of the forms customarily employed for administration of therapeutically active substances but the preferred types are those suitable for oral administration and especially tablets, pills, and capsules including the substance. The tablets and pills may be formulated in manner, known per se with one or more pharmacologically acceptable diluents or excipients such as lactose or starch, and include materials of a lubricating nature such as calcium stearate. Capsules made of absorbable material, such as gelatin, may contain the active substance alone or in admixture with a.solid or liquid diluent. Liquid preparations may be in the form of suspensions, emulsions, syrups or elixirs of the active substance in water or other liquid medium commonly used for making orally acceptable pharmaceutical formulations, such as liquid paralfin, or a syrup or elixir base. The active substance may also be made up in a form suitable for parenteral administration, i.e., as a suspension or emulsion in sterile water or an organic liquid usually employed for injectable preparations, for example vegetable oil such as olive oil, or a sterile solution in an organic solvent.
When used for therapeutic purposes, the compounds of this invention may be employed directly or in the form of their physiologically acceptable non-toxic acid addition salts, i.e., salts which are not harmful to the animal organism when used in therapeutic doses, derived from inorganic acids such .as the hydrohalic acids, for example, hydrochloric or hydrobromic acid, and from organic acids, such as citric maleic, fumaric, tartaric and succinic acids.
The preferred compounds of this invention are those wherein R is hydrogen, Y is lower alkylene (e.g., ethylene) when n is 1, and Z is CH CH. The most preferable compounds of this invention are N-[2-(l(l,l1-dihydro-SH-dibenzo [a,d] cyclohepten-S-yDethyl]-l-phenyl-2- aminopropane and N-[2-(fiuoren-9-ylidene)ethy1]-1-phenyI-Z-aminoprop-ane and the pharmaceutically acceptable nontoxic acid addition salts thereof.
The compounds of this invention may be prepared according to the processes of this invention, by first reacting a 1-phenyl-aminoalkane, for example, dl-l-phenyl- Z-aminopropane or dl-l-phenyl-Z-aminobutane, with an aldehyde of the general formulawherein Y, n and R are as hereinbefore defined to yield a compound of the formula wherein R, R, Y and n are as hereinbefore defined.
These compounds may then be hydrogenated as by catalytic hydrogenation, employing as a catalyst, Raney nickel, to yield compounds of the formula:
wherein R, R, Y and n are as hereinbefore defined.
The aldehydes employed as starting materials may be prepared by condensing a ketone of the formula wherein R, Y and n are as hereinbefore defined, under the influence of a condensing agent such 'as sodamide with acetylene in a medium of liquid ammonia to yield an acetylenic compound of the formula HCEC and causing isomerization of the acetylenic compound by treatment with acid to give aldehydes of the general formula set forth hereinabove.
Acid addition salts of the compounds of this invention may be prepared by methods known per se. For example, the base may be treated with the equivalent quantity of the acid in an inert solvent such as diethyl ether.
The following examples, in which the temperatures are in degrees centigrade, illustrate the invention.
EXAMPLE I N-[2-(10,1I-dihydro-SH-dibenzo [a,d]cyclhept-5-yliderze) ethyl] -1-phenyI-Z-aminopropane hydrochloride A mixture of 0.01 mol. of 10,11-dihydro-H-dibenzo [a,d]cyclohept-5-ylidene acetaldehyde, 0.01 mol. of 1- phenyl-Z-aminopropane, 25 ml. of benzene and anhydrous sodium sulphate is left standing overnight. The mixture is filtered and the filtrate concentrated under reduced pressure. To the residue is added 50 ml. of ethanol and 0.5 g. of sodium borohydride. The mixture is boiled under reflux for about one hour. It is then diluted with water. The oily layer is separated, mixed with ether and the ethereal solution washed three times with water. Hydrochloric acid (2 N) is then added and the precipitated hydrochloride is filtered otf. N-[2-(10,11- dihydro 5H dibenzo[a,d]cyclohept-S-ylidene)ethyl]-1- phenyl-Z-aminopropane hydrochloride is obtained in 88% yield. The compound melts at about 198-200 after crystallization from an ethanol-ether mixture.
Analysis.Calcd. for C H NCl: C, 80.07%; H, 7.24%; N, 3.59%. Found: C, 79.76%; H, 7.23%; N, 3.67%.
The 10,11-dihydro-5H-dibenzo[=a,d]cyclohept-S-ylidene acetaldehyde used as a starting material can be prepared from 10,1l-dihydro-SH-dibenzo[a,d]cyclohepten- 5-one in the following way:
A one litre flask is fitted with a dropping-funnel, a gas-inlet tube filled with solid potassium hydroxide, and a condenser to the upper end of which a tube filled with solid potassium hydroxide is attached. Flask and condenser are cooled with solid carbon dioxide in acetone. From a gas cylinder a quantity of about 200-250 ml. of ammonia is condensed into the flask through the tube filled with potassium hydroxide. Another flask, fitted with an inlet tube nearly reaching to the bottom, an outlet tube and an ascending tube is filled with water. The inlet tube is connected with two washing-bottles placed in series and filled with concentrated sulphuric acid and, moreover, with a tower filled with glass-wool. The latter system is connected with a supply of nitrogen gas. The air is completely replaced by nitrogen by bubbling same through the system. The nitrogen supply is switched off and a stream of acetylene gas passed through the flask containing water to remove acetone vapor stemming from the acetone soaked diatom aceous earth, wherein the acetylene is dissolved in the cylinder. The outlet of the tower is then connected with the inlet tube of the flask, containing the liquid ammonia. 0.2 g. atom of sodium in the form of small pieces is added to the ammonia, whilst acetylene is being passed through. If the sodium is added too rapidly the solution turns blue. When the total quantity of sodium has been added (time needed about 30 minutes) the stream of acetylene is throttled down, and thereafter 0.2 mol. of 10,11-dihydro- 5H-dibenzo[a,d]cycloheptan-S-one (the preparation of 4 which is described in Ber. 83, 367-371 (1950)) dissolved in about 350 ml. of ether is added during the course of about 45 minutes. Then the acetylene supply is cut off, and the reaction mixture is left to react at a temperature of about 60 to -50. The flask is kept standing overnight without stirring or cooling so as to let the ammonia evaporate.
The reaction mixture is then diluted with water, the ether layer is separated, extracted with water and dried with anhydrous sodium sulphate. The ethereal solution is concentrated after filtration, and petroleum ether (boiling range 28-40) is added to the residue. The precipitated solid is collected and crystallized from petroleum ether (boiling range 40-60"). 38.6 g. (yield 82%) of 5 ethynyl 10,1l-dihydro-SI-I-dibenzo[a,d]cycloheptan- 5-ol, melting at 725-73, is obtained.
Analysis.-Calcd. for C H O: C, 87.14%; H, 6.02%. Found: C, 86.54%; H, 6.03%.
To a refluxing mixture of 50 ml. of ethanol (95%), 15 ml. of water and 5 g. of concentrated sulphuric acid, there is added over a period of 30 minutes 10 g. of 5- ethynyl 10,1l-dihydro-SH-dibenzo[a,d]cycloheptan-5-ol dissolved in 25 ml. of ethanol (95%). At the end of the addition, the reaction mixture is boiled under reflux for about 15 minutes and then poured onto ice after chilling. The resulting solid is filtered off and crystallized from petroleum ether (boiling range 4060). 10,11-dihydro- 5H-dibenzo[a,d]cyclohept-S-ylidene acetaldehyde is obtained in yield; its melting point is 70.5-72.
EXAMPLE II N-[Z- (flu0ren-9-ylidene) ethyl] -1-phenyl-2- aminopropane hydrochloride Following the procedure described in Example I but substituting 9-fluorenylidene acetaldehyde for the cyclohept 5 ylidene acetaldehyde, N [2-(fiuoren-9-ylidene) ethyl]-1-phenyl-2 arninopropane is prepared. Its hydrochloride, melting at about 194 194.5, is obtained in 87% yield.
Analysis.Calcd. for C H NCl: C, 79.65%; H, 6.68%; N, 3.87%. Found: C, 79.25%; H, 7.02%; N, 3.67%.
The 9-l'luorenylidene acetaldehyde used as a starting material can be prepared from fluorenone in the following way.
Following the procedure described in Example I for the preparation of 5-ethynyl-10,1l-dihydro-SH-dibenzo [=a,d]cycloheptan-5-ol but substituting fluorenone for the dibenzocycloheptenone, 9-ethynylfluoren-9-ol is prepared. The fluorenone has to be added to the ether portionwise, owing to its poor solubility in the said solvent. 18.0 g. of fluorenone yielded 18.0 g. (87.4%) of 9-ethynylfluoren-9-ol, melting point 107-l08 C., previously described by G. F. Hennion, J. Am. Chem. Soc., 77, 3253 (1955).
Following the procedure described in Example I for the preparation of 10,1l-dihydro-SH-dibenzo[-a,d]cyclohept-S-ylidene acetaldehyde but substituting 9-ethynylfluoren-9-ol for the 5-ethynyl-10,1l-dihydro-SH-dibenzo [a,d]cycloheptan-5-ol, fluoren-9-ylidene acetaldehyde is prepared in 66% yield. The compound, which has been described previously by Hennion, J. Am. Chem. Soc. 77, 3253 (1955) melts at 116.5-117.5.
EXAMPLE III N-[2-(10,11-dihydro-5H-dibenzo[a,d]cyclol1ept-5-yl) ethyl]-1-phenyI-Z-aminopropane hydrochloride 0.01 mol. of N [2 (10,11 dihydro-5H-dibenzo[a,d] cyclohept 5 ylidene)ethyl] l-phenyl-Z-aminopropane hydrochloride, prepared as described in Example I, is dissolved in ethanol. A solution of 0.0125 mol. of sodium hydroxide in 5 ml. of water is added, followed by about 1 g. of Raney nickel. The flask containing the mixture is connected with a supply of hydrogen and the compound hydrogenated under atmospheric pressure. After the theoretical amount of hydrogen has been taken up, the Raney nickel is filtered off and the filtrate concentrated by distillation under reduced pressure. To the residue ether is added, the ethereal solution is dried with sodium sulphate, filtered and acidified with an ethereal solution of hydrogen chloride. The precipitated hydrochloride of N [2 (10,1l-dihydro-SH-dibenzo[a,d]cyclohept-S-yl) ethyl]-l-phenyl-Z-arninopropane is filtered off and crystallized from a mixture of ethanol and ether. Yield 73.5%. Melting point 224-225 Analysis.-Calcd. for C H NCI: C, 79.66%; H, 7.71%; N, 3.57%. Found: C, 79.88%; H, 7.57%; N, 3.69%.
EXAMPLE IV N- [2-(flu0reu-9-yl) ethyl] -1-phenyl-2-aminopropane hydrochloride Following the procedure described in Example III but substituting N [2-(fluoren-9-ylidene)ethyl]-1-phenyl-2- aminopropane hydrochloride for the N-[2-(10,11-dihydro 5H dibenzo [-a,d] cyclohept 5 ylidene)ethyl] 1- phenyl-2-aminopropane hydrochloride, N-[2-(fiuoren-9- yl)ethyl]-1-pheny1-2-aminopropane hydrochloride is obtained. Yield 74%. Melting point 192-193".
Analysis.Calcd. for C H NCl: C, 79.21%; H, 7.10%; N, 3.85%. Found: C, 79.78%; H, 7.14%; N, 3.84%.
This invention may be variously otherwise embodied within the scope of the appended claims.
What is claimed is:
1. A compound of the formula wherein R is lower alkyl; R is selected from the group consisting of hydrogen, halogen, and lower alkyl; Y is selected from the group consisting of oxygen and sulfur; and Z is selected from the group consisting of CH CH and CH=C.
2. The pharmaceutically acceptable non-toxic acid addition salts of the compounds of claim 1.
3. A compound of the formula wherein R, R, and Y are as defined in claim 1.
OTHER REFERENCES Provita et al., J. Med. Pharm. Chem, Vol. 4, pages 411-415 (1961), RS 1'15.
JOHN D. RANDOLPH, Primary Examiner.

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1. A COMPOUND OF THE FORMULA
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US3480624A (en) * 1964-06-01 1969-11-25 Rhone Poulenc Sa Dibenzocycloheptatriene derivatives
US4464301A (en) * 1981-02-10 1984-08-07 Groupement D'interet Economique Centre International De Recherches Dermatologiques C.I.R.D. 1,8-Dihydroxy-9-anthrones derivatives substituted in the 10-position by an unsaturated radical and their use in human and veterinary medicine
WO1997046549A1 (en) * 1996-06-05 1997-12-11 Novartis Ag Anti-neurodegeneratively effective xanthene derivatives

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US3258459A (en) * 1962-08-30 1966-06-28 Squibb & Sons Inc Method for the preparation of n-monosubstituted-secondary aminoalkyl derivatives of polycyclic compounds
US3258488A (en) * 1963-08-12 1966-06-28 Colgate Palmolive Co Dibenzo[a, d]cycloheptene derivatives
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US3073847A (en) * 1959-02-12 1963-01-15 Hoffmann La Roche 9-(3-amino-1-propynyl) derivatives of 9-xanthenols and 9-thioxanthenols and a process for their preparation
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Cited By (4)

* Cited by examiner, † Cited by third party
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US3480624A (en) * 1964-06-01 1969-11-25 Rhone Poulenc Sa Dibenzocycloheptatriene derivatives
US3442949A (en) * 1965-05-03 1969-05-06 Merck & Co Inc Method for preparing 5-(3-aminopropylidene)-5h-dibenzo - (a,d) - 10,11 - dihydrocycloheptenes
US4464301A (en) * 1981-02-10 1984-08-07 Groupement D'interet Economique Centre International De Recherches Dermatologiques C.I.R.D. 1,8-Dihydroxy-9-anthrones derivatives substituted in the 10-position by an unsaturated radical and their use in human and veterinary medicine
WO1997046549A1 (en) * 1996-06-05 1997-12-11 Novartis Ag Anti-neurodegeneratively effective xanthene derivatives

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FI42543B (en) 1970-06-01
FR3974M (en) 1966-03-07
DE1214688B (en) 1966-04-21
CH455754A (en) 1968-05-15
GB1006588A (en) 1965-10-06
BR6353836D0 (en) 1973-07-12
FR1450391A (en) 1966-06-24
NL133997C (en)
ES292867A1 (en) 1964-04-01
FI44241B (en) 1971-06-30
NL299449A (en)
DK111174B (en) 1968-06-24
DK109925C (en) 1968-08-05
SE313301B (en) 1969-08-11
BE638839A (en)

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