NO145274B - PROCEDURE FOR THE PREPARATION OF A 1-BENZOYL-2- (2`, 6`-DICHLORPHENYLAMINO) -2-IMIDAZOLINE AND OF THEIR SALTS - Google Patents

PROCEDURE FOR THE PREPARATION OF A 1-BENZOYL-2- (2`, 6`-DICHLORPHENYLAMINO) -2-IMIDAZOLINE AND OF THEIR SALTS Download PDF

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NO145274B
NO145274B NO762439A NO762439A NO145274B NO 145274 B NO145274 B NO 145274B NO 762439 A NO762439 A NO 762439A NO 762439 A NO762439 A NO 762439A NO 145274 B NO145274 B NO 145274B
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benzoyl
imidazoline
salts
preparation
formula
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NO762439L (en
NO145274C (en
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Rudolf Franzmair
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Chemie Linz Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/44—Nitrogen atoms not forming part of a nitro radical
    • C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
    • 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
    • A61P9/12—Antihypertensives

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Cosmetics (AREA)

Description

Fra OE-PS 248.428, 250.344og 250.345 er det kjent at 2-arylamino-2-imidazolin, og særlig forbindelser. 2-(2<1>,6'-diklorfenylamino)-2-imidazolin har en utpreget hypotensiv virkning, som er kombinert med en sedativ virkning. From OE-PS 248.428, 250.344 and 250.345 it is known that 2-arylamino-2-imidazoline, and especially compounds. 2-(2<1>,6'-dichlorophenylamino)-2-imidazoline has a pronounced hypotensive effect, which is combined with a sedative effect.

Fra BE-PS 741.947 er videre N-aroylderivater From BE-PS 741,947 are further N-aroyl derivatives

av disse 2-arylamino-2-imidazoliner, f.eks. 2-f_ N-benzoyl-(2 ', 6 ' -diklorfenyl) -amino ~ 2-2-imidazolin kjent, som like-ledes utviser denne hypotensive virkning sammen med en sedi-erende virkning. Forbindelsene tilveiebringes ved aroyler-ing av de frie 2-arylamino-2-imidazoliner med passende syre-klorider av aromatiske karbonsyrer, hvorunder syreresten blir utbyttet mot det hydrogen som er bundet på anilin-nitrogenet. of these 2-arylamino-2-imidazolines, e.g. 2-f_N-benzoyl-(2',6'-dichlorophenyl)-amino ~ 2-2-imidazoline is known, which likewise exhibits this hypotensive effect together with a sedative effect. The compounds are provided by aroylation of the free 2-arylamino-2-imidazolines with suitable acid chlorides of aromatic carboxylic acids, during which the acid residue is exchanged for the hydrogen bound on the aniline nitrogen.

Det er nå oppdaget at man ved omsetning av 2,6-diklorfenylisocyaniddihalogenider med N-benzoyl,etylendiamin oppstår et benzoylderivat av 2-(2',6'-diklorfenylamino)-2-imidazolin med interessante farmakologiske egenskaper, hvor benzoylresten ikke er bundet til anilinkvelstoffet, men, som klart fremgår av syntesen, til imidazolinkvelstoffet. Den- It has now been discovered that by reacting 2,6-dichlorophenylisocyanide dihalogenides with N-benzoyl,ethylenediamine a benzoyl derivative of 2-(2',6'-dichlorophenylamino)-2-imidazoline with interesting pharmacological properties is formed, where the benzoyl residue is not bound to the aniline nitrogen, but, as is clear from the synthesis, to the imidazoline nitrogen. It-

ne forbindelsen er en strukturisomer av de benzoylderivater som er beskrevet i BE-PS 7 41.9 47, noe som kan påvises ved fysikalske målinger, bl.a. av blandesmeltepunktet og pKa-verdien. ne compound is a structural isomer of the benzoyl derivatives described in BE-PS 7 41.9 47, which can be demonstrated by physical measurements, i.a. of the mixing melting point and the pKa value.

Den foreliggende oppfinnelse vedrører derfor The present invention therefore concerns

en fremgangsmåte til fremstilling av et l-benzoyl-2-(2', 6'-diklorfenylamino)-2-imidazolin med formelen a process for the preparation of a 1-benzoyl-2-(2', 6'-dichlorophenylamino)-2-imidazoline of the formula

eller av disse forbindelsers salter, karakterisert ved at 2,6-diklorfenylisocyaniddihalogenid med den generelle formel or of the salts of these compounds, characterized in that 2,6-dichlorophenylisocyanide dihalogenide with the general formula

hvor X er halogen, fortrinnsvis klor, omsettes med N-benzoyletylendiamin i et oppløsningsmiddel som er inerte overfor reaksjonsdeltagerne ved temperaturer fra 0°C til kokepunktet for det anvendte oppløsningsmiddel under tilsats av syrebindende midler. where X is halogen, preferably chlorine, is reacted with N-benzoylethylenediamine in a solvent which is inert towards the reaction participants at temperatures from 0°C to the boiling point of the solvent used with the addition of acid-binding agents.

N-benzoyletylendiamin er kjent fra litteraturen, og fremstilles etter Aspinall, J. Org. Chem. 6.895.899 (1941) eller analogt med dette. N-benzoylethylenediamine is known from the literature, and is prepared according to Aspinall, J. Org. Chem. 6,895,899 (1941) or analogous thereto.

Omsetningen ifølge oppfinnelsen kan prinsipielt gjennomføres ved alle de metoder som er kjent, for acylerings-reaksjoner med den innskrenkning at bare de oppløsningsmidler og syrebindende midler kan anvendes som enten ikke reagerer The reaction according to the invention can in principle be carried out by all the known methods for acylation reactions with the restriction that only solvents and acid-binding agents can be used which either do not react

med eller som bare reagerer meget langsomt med et aryliso-cyaniddiklorid med formelen II, slik at den ønskede omsetning with or which reacts only very slowly with an arylisocyanide dichloride of the formula II, so that the desired reaction

ikke eller bare uvesentlig blir påvirket. Som løsningsmidler kommer såvel apolare som delvis polare oppløsningsmidler på tale, f.eks. bensen, toluen, Xylen, cykloheksan, halogenerte hydrokarboner, såsom f.eks. metylenklorid, kloroform, eter som f.eks. dietyleter, tetrahydrofuran, dioksan, estere såsom f.eks. eddiksyreetylester, og også polare oppløsningsmidler såsom alkoholer, og særlig alkoholer med mer enn 2 C-atomer acetonitril, dimetylformamid,dimetylsulfoksyd. not or only immaterially affected. Solvents include both apolar and partially polar solvents, e.g. benzene, toluene, xylene, cyclohexane, halogenated hydrocarbons, such as e.g. methylene chloride, chloroform, ether such as diethyl ether, tetrahydrofuran, dioxane, esters such as e.g. acetic acid ethyl ester, and also polar solvents such as alcohols, and especially alcohols with more than 2 C atoms, acetonitrile, dimethylformamide, dimethylsulfoxide.

Reaksjonen kan utføres heterogent eller homo-gent. Ved heterogene reaksjoner er særlig vandig natron eller kalilut egnet som syrebindende middel og ved homogene reaksjoner natrium eller kaliumalkoholater. The reaction can be carried out heterogeneously or homogeneously. In the case of heterogeneous reactions, aqueous sodium or potassium hydroxide is particularly suitable as an acid-binding agent, and in the case of homogeneous reactions, sodium or potassium alcoholates.

Da de tilveiebragte forbindelser er en As the connections provided are one

svak base, er det foretrukket å arbeide slik at reak-sjonsblandingén,"eventuelt etter inndampning og opp- weak base, it is preferred to work so that the reaction mixture, possibly after evaporation and

løsning i et inert oppløsningsmiddel, såsom benzen eller metylenklorid, blir ekstrahert med fortynnede vandige .syrer fortrinnsvis ln saltsyre, hvoretter de saltsure ekstrakter gjøres alkaliske, hvorunder forbindelsen ifølge oppfinnel- solution in an inert solvent, such as benzene or methylene chloride, is extracted with dilute aqueous acids, preferably hydrochloric acid, after which the hydrochloric acid extracts are made alkaline, during which the compound according to the invention

sen faller ut som krystaller. Etter frafiltrering foretas en omkrystallisering fra et egnet oppløsningsmiddel, f.eks. isopropailol, acetonitril, etylenacetat, benzen eller toluen, hvorunder forbindelsen ifølge oppfinnelsen tilveiebringes med høy renhet. then falls out as crystals. After filtration, recrystallization is carried out from a suitable solvent, e.g. isopropaylol, acetonitrile, ethylene acetate, benzene or toluene, whereby the compound according to the invention is provided with high purity.

Omsetningen gjennomføres ved 0°C og kokepunktet for det anvendte oppløsningsmiddel, fortrinnsvis mellom +10 The reaction is carried out at 0°C and the boiling point of the solvent used, preferably between +10

og +50°C. Reaksjonstiden ligger fortrinnsvis mellom noen timer og 24 timer. and +50°C. The reaction time is preferably between a few hours and 24 hours.

Det er ikke mulig å forutse og det kommer som It is not possible to predict and it will come as

en overraskelse at et amidnitrogen, såsom det som foreligger i N-benzoyletylendiamin, villig reagerer med et halogen i arylisocyaniddihalogenidet også ved milde acyleringsmetoder, såsom en Schotten-Baumann-reaksjon. a surprise that an amide nitrogen, such as that present in N-benzoylethylenediamine, willingly reacts with a halogen in the arylisocyanide dihalogenide even by mild acylation methods, such as a Schotten-Baumann reaction.

Forbindelsene med formel Ia eller Ib er et enhetlig, godt krystallisert produkt. Strukturen i disse forbindelser er foreløbig ikke entydig bestembar, idet man lar det stå åpent om dobbeltbindingen er plasert i imidacolinringen (Ia) eller eksocyklisk (Ib). Forbindelsene har meget interessante farmasøytiske egenskaper. De har nesten like sterkt blodtrykksenkende virkning som forbindelser som i stedet for benzoylresten har et hydrogenatom og som ved benzoylderivat av denne forbindelse som er substituert på anilihkvelstoffet og som er beskrevet i BE-PS 741.947, samtidig som den sedative virkningskomponent er mindre sterkt utpreget. Ved anvendelse av de foreliggende forbindelser som hypotensivum faller derfor bl.a. den uønskede bivirk- The compounds of formula Ia or Ib are a uniform, well crystallized product. The structure of these compounds cannot yet be determined unambiguously, leaving it open whether the double bond is placed in the imidacoline ring (Ia) or exocyclic (Ib). The compounds have very interesting pharmaceutical properties. They have almost as strong a blood pressure-lowering effect as compounds which instead of the benzoyl residue have a hydrogen atom and as with the benzoyl derivative of this compound which is substituted on the anil nitrogen and which is described in BE-PS 741,947, at the same time that the sedative effect component is less pronounced. When using the present compounds as a hypotensive agent, therefore, i.a. the unwanted side effect

ning som tretthet bort. Forbindelsen med formel Ia eller Ib opptas utmerket gjennom munnen. ning as fatigue gone. The compound of formula Ia or Ib is excellently absorbed orally.

Mangelen på sedativ eller sentraldempende virkning, kan lett påvises ved å fastslå tilstedeværelsen av carotissinusreflekser i bedøvede kaniner etter til- The lack of sedative or central depressant action can be easily demonstrated by determining the presence of carotid sinus reflexes in anesthetized rabbits after the

førsel av den nevnte forbindelse i doser på 100 mikrogram/kg. Denne refleksen er ellers ved tilførsel av den samme dose administration of the said compound in doses of 100 micrograms/kg. This reflex is otherwise when the same dose is administered

av 2-(21,6'-diklorfenylamino)-2-imidazolin nesten full-stendig undertrykket. Dette blir også klart ved den ufor-andrede adferd i våkne mus etter tilførsel av 5 eller 10 mg/kg av l-bensoyl-2-(2 *,6 *-diklorfenylamino)-2-imidasolin. of 2-(21,6'-dichlorophenylamino)-2-imidazoline almost completely suppressed. This is also clear from the unchanged behavior in awake mice after administration of 5 or 10 mg/kg of 1-benzoyl-2-(2*,6*-dichlorophenylamino)-2-imidazoline.

Forbindelsen med formel Ia eller Ib kan i medisinen anvendes som et blodtrykkdempende middel i alle farmasøytisk tilberedningsformer, såsom tabletter, drageer, kapsler, suppositorier, emulsjoner, løsninger eller injek-sjonsløsninger. The compound of formula Ia or Ib can be used in medicine as an antihypertensive agent in all pharmaceutical preparation forms, such as tablets, dragees, capsules, suppositories, emulsions, solutions or injection solutions.

Alt etter anvendelsesområde brukes enten den Depending on the area of application, either is used

fri base eller saltene. Som salter tjener f.eks. salter med uorganiske eller organiske syrer, såsom hydrohalogenider, fosfater, oksalater, 8-klorteofyllinater eller salter med sure, syntetiske harpikser. free base or the salts. As salts serve e.g. salts with inorganic or organic acids, such as hydrohalides, phosphates, oxalates, 8-chlorotheophyllinates or salts with acidic synthetic resins.

Fremgangsmåten ifølge oppfinnelsen vil bli nærmere belyst ved de etterfølgende eksempler. The method according to the invention will be explained in more detail by the following examples.

Eksempel 1: Example 1:

1,64 g (10 mmol) N-benzoyletylendiamin opp-løses i 100 ml benzen og blandingen tilsettes 25 ml vann, oppvarmes under kraftig omrøring til 50°C mens der samtidig tilsettes en oppløsning av 2,31 g (10 mmol) 2,6-diklorfenylisocyaniddiklorid i 20 ml absolutt benzen og 20 ml ln NaOH 1.64 g (10 mmol) of N-benzoylethylenediamine is dissolved in 100 ml of benzene and 25 ml of water is added to the mixture, heated with vigorous stirring to 50°C while at the same time a solution of 2.31 g (10 mmol) 2 is added, 6-dichlorophenylisocyanide dichloride in 20 ml absolute benzene and 20 ml ln NaOH

i løpet av 75 minutter. Blandingen omrøres i 3 timer ved within 75 minutes. The mixture is stirred for 3 hours at

50°C, avkjøles til værelsestemperatur og de to faser skilles. Vannfasen ekstraheres.en gang til med 100 ml benzen. Begge benzenfasene slås sammen/ vaskes med vann og ekstraheres 3 ganger med 75 ml ln saltsyre. De saltsure ekstrakter slås sammen, vaskes en gang med eter og gjøres alkaliske med soda, og dette tilveiebringer 650 mg (19,4 %) urenset 1-benzoyl-2-(2',6'-diklorfenylamino)-2-imidazolin. Etter omkrystallisering fra isopropanol tilveiebringes 480 mg . Smeltepunkt 160 - 162°C. 50°C, cooled to room temperature and the two phases separated. The water phase is extracted once more with 100 ml of benzene. Both benzene phases are combined/washed with water and extracted 3 times with 75 ml ln hydrochloric acid. The hydrochloric acid extracts are combined, washed once with ether and made alkaline with sodium hydroxide to provide 650 mg (19.4%) of crude 1-benzoyl-2-(2',6'-dichlorophenylamino)-2-imidazoline. After recrystallization from isopropanol, 480 mg are obtained. Melting point 160 - 162°C.

Eksempel 2: Example 2:

3,28 g (20 mmol) N-benzoyletylendiamin omsettes med 4,62 g (20 mmol) 2,6-diklorfenylisocyaniddiklorid og 40 ml ln NaOH ved 10 - 15°C på tilsvarende måte son i eksempel 1. Dette gir 1,20 g (18,0% av teoretisk utbytte) urenset 1-benzoy1-2-(2',6'-diklorfenylamino)-2- imidazolin. Etter omkrystallisering fra isopropanol tilveiebringes 950 mg (fra 14,2 % av teoretisk utbytte), med smeltepunkt = 160 - 162°C. 3.28 g (20 mmol) of N-benzoylethylenediamine is reacted with 4.62 g (20 mmol) of 2,6-dichlorophenylisocyanide dichloride and 40 ml of ln NaOH at 10 - 15°C in a similar manner as in example 1. This gives 1.20 g (18.0% of theoretical yield) impure 1-benzoyl-2-(2',6'-dichlorophenylamino)-2-imidazoline. After recrystallization from isopropanol, 950 mg is obtained (from 14.2% of theoretical yield), with melting point = 160 - 162°C.

Eksempel 3: Example 3:

1,64 g (10 mmol) N-benzoyletylendiamin oppløses i 60 ml absolutt THF, tilsettes 0,48 g (20 mmol) NaH (eventuelt 0,90 g av en 55 %'s dispersjon) og blandingen omrøres i'30 minutter til gassutviklingen er avsluttet. Deretter tilsettes dråpevis under omrøring ved værelsestemperatur en oppløsning av 2,31 g (10 mmol) 2,6-diklorfenylisocyaniddiklorid i 20 ml absolutt THF, hvorunder reaksjonsblandingen blir noe oppvarmet. Dette omrøres i 2 timer ved værelsestemperatur, hvorunder eventuelt tilstedeværende NaH forsiktig oppløses i vannet og inndampes.; Residuet tas opp i metylenklorid og ekstraheres 3 ganger med 75 ml ln saltsyre. De saltsure ekstrakter slås sammen og gjøres alkalisk med sodaopp-løsning, hvorunder et faststoff utkrystalliserer. Dette fra-filtreres og omkrystalliseres fra isopropanol mens det frem-deles er fuktig. Dette gir 1,02 g 2-benzoyl-2-(2',6'-diklor-fenylamino) -2-imidazolin (som er 30,5 % av teoretisk utbytte) med smeltepunkt 160 - 162°C. 1.64 g (10 mmol) of N-benzoylethylenediamine is dissolved in 60 ml of absolute THF, 0.48 g (20 mmol) of NaH (optionally 0.90 g of a 55% dispersion) is added and the mixture is stirred for 30 minutes more gas development has ended. A solution of 2.31 g (10 mmol) of 2,6-dichlorophenylisocyanide dichloride in 20 ml of absolute THF is then added dropwise with stirring at room temperature, during which the reaction mixture is slightly heated. This is stirred for 2 hours at room temperature, during which any NaH present is carefully dissolved in the water and evaporated.; The residue is taken up in methylene chloride and extracted 3 times with 75 ml of hydrochloric acid. The hydrochloric acid extracts are combined and made alkaline with soda solution, during which a solid crystallizes out. This is filtered off and recrystallized from isopropanol while it is still moist. This gives 1.02 g of 2-benzoyl-2-(2',6'-dichloro-phenylamino)-2-imidazoline (which is 30.5% of theoretical yield) with melting point 160 - 162°C.

Claims (2)

1. Fremgangsmåte for fremstilling av et l-benzoyl-2- (21,61-diklorfenylamino)-2-imidazolin med formelen eller salter av dette, karakterisert ved at 2,6-diklorfenylisocyaniddihalogenid med den generelle formel hvor X er halogen, fortrinnsvis klor, omsettes med benzoyletylendiamin i et oppløsningsmiddel som er inert overfor reaksjonsdeltagerne ved temperaturer fra 0°C til kokepunktet for det anvendte oppløsningsmiddel under tilsats av et syrebindende middel, hvorunder den tilveiebragte forbindelse med formelen (Ia) eller (Ib) isoleres som den frie base eller son et salt med en uorganisk eller organisk syire.1. Process for the preparation of a 1-benzoyl-2-(21,61-dichlorophenylamino)-2-imidazoline of the formula or salts thereof, characterized in that 2,6-dichlorophenylisocyanide dihalogenide with the general formula where X is halogen, preferably chlorine, is reacted with benzoylethylenediamine in a solvent which is inert towards the reaction participants at temperatures from 0°C to the boiling point of the solvent used with the addition of an acid-binding agent, during which the provided compound of the formula (Ia) or (Ib ) is isolated as the free base or a salt with an inorganic or organic acid. 2. Fremgangsmåte ifølge krav 1, karakter i-sert ved at omsetningen gjennomføres ved temperaturer fra +10°C til + 50°C.2. Method according to claim 1, characterized in that the reaction is carried out at temperatures from +10°C to +50°C.
NO762439A 1975-09-25 1976-07-12 PROCEDURE FOR THE PREPARATION OF A 1-BENZOYL-2- (2`, 6`-DICHLORPHENYLAMINO) -2-IMIDAZOLINE AND OF THEIR SALTS NO145274C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
AT735575A AT339897B (en) 1975-09-25 1975-09-25 PROCESS FOR PREPARING THE NEW 1-BENZOYL-2- (2 ', 6'-DICHLOROPHENYLAMINO) -2-IMIDAZOLINE AND THE SALT THEREOF

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NO762439L NO762439L (en) 1977-03-28
NO145274B true NO145274B (en) 1981-11-09
NO145274C NO145274C (en) 1982-02-17

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JP (1) JPS5239675A (en)
AT (1) AT339897B (en)
BG (1) BG35040A3 (en)
CA (1) CA1062267A (en)
CH (1) CH601253A5 (en)
CS (1) CS196324B2 (en)
DD (1) DD126907A1 (en)
DK (1) DK144565C (en)
ES (1) ES451829A1 (en)
FI (1) FI63752C (en)
NL (1) NL7608971A (en)
NO (1) NO145274C (en)
PL (1) PL100503B1 (en)
PT (1) PT65438B (en)
RO (1) RO69914A (en)
SE (1) SE439010B (en)
SU (1) SU604488A3 (en)
YU (1) YU39360B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MTP837B (en) * 1977-11-07 1979-10-22 Hoffman La Roche And Co Aktien Derivatives 2 finino-imidazolidire
DE2811847A1 (en) 1978-03-17 1979-09-20 Lentia Gmbh NEW ARYLAMINOIMIDAZOLINE DERIVATIVES, THEIR PRODUCTION AND USE AS MEDICINAL PRODUCTS
DE3200258A1 (en) * 1982-01-07 1983-07-21 Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München SUBSTITUTED 1-BENZOYL-2-PHENYLIMINO IMIDAZOLIDINE, THE ACID ADDITION SALTS THEREOF, METHOD FOR THE PRODUCTION THEREOF AND THE MEDICINAL PRODUCTS CONTAINING THE SAME

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NO762439L (en) 1977-03-28
CH601253A5 (en) 1978-06-30
RO69914A (en) 1981-06-30
NO145274C (en) 1982-02-17
CA1062267A (en) 1979-09-11
JPS5239675A (en) 1977-03-28
ATA735575A (en) 1977-03-15
SE439010B (en) 1985-05-28
ES451829A1 (en) 1977-11-01
FI63752B (en) 1983-04-29
FI63752C (en) 1983-08-10
PT65438B (en) 1978-02-09
DK144565B (en) 1982-03-29
JPS5333592B2 (en) 1978-09-14
PT65438A (en) 1976-09-01
SE7609391L (en) 1977-03-26
NL7608971A (en) 1977-03-29
SU604488A3 (en) 1978-04-25
YU39360B (en) 1984-10-31
FI762025A (en) 1977-03-26
BG35040A3 (en) 1984-01-16
DK144565C (en) 1982-09-13
DD126907A1 (en) 1977-08-17
AT339897B (en) 1977-11-10
DK354376A (en) 1977-03-26
PL100503B1 (en) 1978-10-31
YU184876A (en) 1982-06-30
CS196324B2 (en) 1980-03-31

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