FR2459797A2 - PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION - Google Patents

PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION Download PDF

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Publication number
FR2459797A2
FR2459797A2 FR7916029A FR7916029A FR2459797A2 FR 2459797 A2 FR2459797 A2 FR 2459797A2 FR 7916029 A FR7916029 A FR 7916029A FR 7916029 A FR7916029 A FR 7916029A FR 2459797 A2 FR2459797 A2 FR 2459797A2
Authority
FR
France
Prior art keywords
phenyl
ethanol
therapeutic application
piperazine derivatives
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
FR7916029A
Other languages
French (fr)
Other versions
FR2459797B2 (en
Inventor
Henry Najer
Philippe Michel
Jacques Manoury
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synthelabo SA
Original Assignee
Synthelabo SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from FR7822672A external-priority patent/FR2432515A1/en
Priority claimed from FR7833105A external-priority patent/FR2442234A2/en
Application filed by Synthelabo SA filed Critical Synthelabo SA
Priority to FR7916029A priority Critical patent/FR2459797A2/en
Priority to DE19792930440 priority patent/DE2930440A1/en
Priority to GB7926224A priority patent/GB2027703A/en
Priority to AU49309/79A priority patent/AU4930979A/en
Priority to NL7905810A priority patent/NL7905810A/en
Priority to NZ191140A priority patent/NZ191140A/en
Priority to IT24749/79A priority patent/IT1123497B/en
Priority to LU81562A priority patent/LU81562A1/en
Priority to DK321479A priority patent/DK321479A/en
Priority to IL57920A priority patent/IL57920A0/en
Priority to NO792502A priority patent/NO792502L/en
Priority to PT70007A priority patent/PT70007A/en
Priority to SE7906507A priority patent/SE7906507L/en
Priority to JP9858679A priority patent/JPS5522690A/en
Priority to ES483003A priority patent/ES483003A1/en
Priority to BE0/196538A priority patent/BE877994A/en
Priority to FI792401A priority patent/FI792401A/en
Priority to GR59710A priority patent/GR69703B/el
Publication of FR2459797A2 publication Critical patent/FR2459797A2/en
Publication of FR2459797B2 publication Critical patent/FR2459797B2/fr
Application granted granted Critical
Granted legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • 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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Abstract

LE (METHYLTHIO-3 PHENYL)-4 PIPERAZINYL-1-2 ETHANOL ET SES SELS D'ADDITION AUX ACIDES PHARMACEUTIQUEMENT ACCEPTABLES. APPLICATION EN THERAPEUTIQUE.(METHYLTHIO-3 PHENYL) -4 PIPERAZINYL-1-2 ETHANOL AND ITS ADDITIONAL SALTS WITH PHARMACEUTICALLY ACCEPTABLE ACIDS. APPLICATION IN THERAPEUTICS.

Description

ti 24597972459797

Le présent certificat d'addition a pour objet le [(méthyl-  This certificate of addition is for the purpose of

thio-3 phényl)-4 pipérazinyl-1]-2 éthanol, ses sels d'addition aux  thio-3-phenyl) -4-piperazinyl-2 ethanol, its addition salts with

acides pharmaceutiquement acceptables, sa préparation et son ap-  pharmaceutically acceptable acids, its preparation and its

plication en thérapeutique.application in therapy.

Dans le brevet principal ont été décrits les composés de formule  In the main patent, compounds of formula

/> N R2/> N R2

R dans laquelle R1 représente un radical S (O)m R3, S (0)n CF3 ou -SO2 NsR4 R5 dans lequel m est 0, 1 ou 2, n est 1 ou 2, R3 est un radical alkyle de 1 à 10 atomes de carbone et R4 et R5 représentent H ou un radical alkyle de 1 à 4 atomes de carbone ou NR4R5 forment ensemble un hétérocycle pouvant lui-même contenir un autre hétéroatome, et R2 représente un atome d'hydrogène, le radical -CH2 -CH2 -OH ou un  Wherein R1 represents a radical S (O) m R3, S (O) n CF3 or -SO2 NsR4 R5 wherein m is 0, 1 or 2, n is 1 or 2, R3 is an alkyl radical of 1 to 10 carbon atoms and R4 and R5 represent H or an alkyl radical of 1 to 4 carbon atoms or NR4R5 together form a heterocycle which may itself contain another heteroatom, and R2 represents a hydrogen atom, the radical -CH2 -CH2 -OH or a

radical CH2-CH2-O-COR6, CH2-CH2-O-CONHR6 ou CH2- CH2-O-R6 dans les-  radical CH2-CH2-O-COR6, CH2-CH2-O-CONHR6 or CH2-CH2-O-R6 in

quels R6 est un alkyle de 1 à 6 atomes de carbone.  which R6 is an alkyl of 1 to 6 carbon atoms.

Le composé du présent certificat d'addition de formule  The compound of this Formula Addition Certificate

N N - CH2-CH2-OHN N - CH2-CH2-OH

(1) SCH3 est obtenu, par réaction entre la(méthylthio-3 phényl)-4 pipérazine et un composé X CH2 CH2 OH, o X est un halogène ou un groupe ester tel que mésyle ou tosyle (ou par réaction de (I) avec l'oxyde d'éthylène). L'exemple suivant illustre l'invention. Les spectres IR et RMN et  (1) SCH3 is obtained, by reaction between 3- (4-methylthiophenyl) piperazine and a compound X CH2 CH2 OH, where X is a halogen or an ester group such as mesyl or tosyl (or by reaction of (I) with ethylene oxide). The following example illustrates the invention. IR and NMR spectra and

l'analyse ont confirmé la structure du produit.  the analysis confirmed the structure of the product.

Exemple [(méthylthio-3 phényl)-4 piperazinyl-1]-2 éthanol et  Example [3- (3-methylthiophenyl) -2-piperazinyl] ethanol and

son chlorhydrate.its hydrochloride.

Dans un erlenmeyer rodé de 250 ml, équipé d'un agitateur magnétique  In a 250 ml ground flask equipped with a magnetic stirrer

2 24597972 2459797

et d'un réfrigérant à reflux, on introduit 100ml d'éthanol, 10g (0,048 mole) de (méthylthio-3 phényl) - 1 pipérazine (préparée selon le brevet des E.U.A. 2,976,290), 5,5g de carbonate de sodium  and a reflux condenser were charged with 100 ml of ethanol, 10 g (0.048 mole) of (3-methylthiophenyl) piperazine (prepared according to US Patent 2,976,290), 5.5 g of sodium carbonate.

quelques cristaux d'iodure de sodium, 3,7ml de bromlhydrine du glycol.  some crystals of sodium iodide, 3.7ml of glycol bromlhydrin.

On porte à la température de reflux pendant 6 heures, puis on ra-  The temperature is refluxed for 6 hours, then

joute 3,7ml de bromhydrine du glycol et 5,5g de carbonate de sodium. On filtre l'insoluble après 4 heures de reflux; on évapore à sec l'éthanol, on reprend le résidu d'évaporation par de l'eau et on l'alcalinise avec de la soude; on extrait avec du chloroforme; on  3.7 ml of glycol bromhydrin and 5.5 g of sodium carbonate. The insoluble material is filtered off after refluxing for 4 hours; the ethanol is evaporated to dryness, the evaporation residue is taken up in water and basified with sodium hydroxide; extracted with chloroform; we

lave à l'eau, on sèche sur sulfate de sodium et on évapore à sec. -  washed with water, dried over sodium sulphate and evaporated to dryness. -

On obtient une huile qui est transformée directement en chlorhydrate.  An oil is obtained which is converted directly into hydrochloride.

Préparation du sel. On solubilise la base dans un minimum d'alcool absolu, on ajoute goutte à goutte de l'éther chlorhydrique 4,6N,soit 9,3ml. Le chlorhydrate précipite; on le filtre, l'essore et le  Salt preparation. The base is solubilized in a minimum of absolute alcohol, 4.6N hydrochloric ether is added dropwise, ie 9.3 ml. The hydrochloride precipitates; it is filtered, squeezed and

sèche avant de le recristalliser dans l'éthanol. On obtient le pro-  dry before recrystallizing it in ethanol. We get the

duit fondant à 147 C.melting duit at 147 C.

Le composé de l'invention a été soumis à des essais phar-  The compound of the invention has been subjected to pharmaceutical tests.

macologiques, en particulier dans le domaine analgésique, au test de l'injection intrapéritonéale d'acide acétique chez la souris de Koster et coll. (Fed.Proc.1959,18,42) modifié par Peterfalvi,Branceni et coll. (Med. Pharmacol.Exp.1966,15,254) dans lequel il a révélé une dose active 50 de 7mg/kg par voie orale; et au test de la plaque  in the analgesic field, in the test of intraperitoneal injection of acetic acid in the mouse of Koster et al. (Fed.Proc.1959,18,42) modified by Peterfalvi, Branceni et al. (Med, Pharmacol.Exp.1966,15,254) in which it revealed an active dose of 50 mg / kg orally; and the plate test

chauffante de Eddy et Leinmbach (J.Pharm.Exp.Therap.1953,107,386).  heated by Eddy and Leinmbach (J.Pharm.Exp.Therap.1953,107,386).

dans lequel les doses actives 50 sont de 50mg/kg à 30mn et de  in which the active doses 50 are 50 mg / kg at 30 minutes and

mg/kg à 60mn.mg / kg at 60mn.

La toxicité aiguë du composé de l'invention, déterminée  Acute toxicity of the compound of the invention, determined

par voie orale sur la souris est de 500mg/kg.  Orally in the mouse is 500mg / kg.

Ces résultats montrent que le composé de l'invention pos-  These results show that the compound of the invention

sède une activité analgésique essentiellement périphérique. En effet la DA50 dans le test de Koster est faible alors que la DA50 dans le  has an essentially peripheral analgesic activity. Indeed the DA50 in the Koster test is weak whereas the DA50 in the

test de la plaque chauffante est plus élevée.  Heating plate test is higher.

Le composé de l'invention peut être utilisé pour les trai-  The compound of the invention can be used for the treatment of

tements de diverses algies, telles que céphalées, névralgies, dou-  various headaches, such as headache, neuralgia,

leurs dentaires, algies rhumatismales et traumatiques, douleurs viscérales. Le composé de l'invention peut à cet effet être présenté  their teeth, rheumatic and traumatic pain, visceral pain. The compound of the invention can for this purpose be presented

sous forme d'administration appropriée pour la voie orale, paren-  as an appropriate administration for the oral route,

térale ou endorectale, par exemple sous la forme de comprimés,  lateral or endorectal, for example in the form of tablets,

gélules,solutions injectables ou suppositoires..... avec un ex-  capsules, injectables or suppositories ..... with an ex-

cipient approprié.appropriate container.

La posologie quotidienne peut aller de 50mg à lO1000mg.  The daily dosage can range from 50mg to 1000mg.

Claims (3)

REVENDICATIONS 1. Le [(méthylthio-3 phényl) -4 pipérazinyl-1] -2 éthanol et  1. [3- (3-Methylthio-phenyl) -1-piperazinyl] ethanol and ses sels d'addition aux acides pharmaceutiquement acceptables.  its pharmaceutically acceptable acid addition salts. 2. Procédé de préparation du composé selon la revendication 1, procédé caractérisé en ce que l'on fait réagir le (méthylthio-3  2. Process for the preparation of the compound according to claim 1, characterized in that the (methylthio-3) is reacted phényl)-4 pipérazine avec le bromo-2 éthanol.  phenyl) -4 piperazine with 2-bromo ethanol. 3. Médicament caractérisé en ce qu'il contient un composé selon  3. Medicinal product characterized in that it contains a compound according to la revendication 1.claim 1.
FR7916029A 1978-08-01 1979-06-22 PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION Granted FR2459797A2 (en)

Priority Applications (18)

Application Number Priority Date Filing Date Title
FR7916029A FR2459797A2 (en) 1978-08-01 1979-06-22 PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION
DE19792930440 DE2930440A1 (en) 1978-08-01 1979-07-26 1-PHENYL PIPERAZINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THE SAME
GB7926224A GB2027703A (en) 1978-08-01 1979-07-27 1-Phenylpiperazine derivatives
AU49309/79A AU4930979A (en) 1978-08-01 1979-07-27 1-phenylpiperazine derivatives
NL7905810A NL7905810A (en) 1978-08-01 1979-07-27 PROCESS FOR PREPARING A PHARMACEUTICAL PREPARATION BASED ON A PIPERAZINE DERIVATIVE, WHICH IS ACTIVE WITH REGARD TO THE CENTRAL NERVOUS SYSTEM AND IS AN PAIN-RELIEF AGENT, PROCESS FOR THE PREPARATION OF THE PIPERAZINE DERIVATIVE PRODUCT AND THE PREPARATOR.
NZ191140A NZ191140A (en) 1978-08-01 1979-07-27 1-phenylpiperazine derivatives pharmaceutical compositions
IT24749/79A IT1123497B (en) 1978-08-01 1979-07-27 PHENYL-1 PIPERAZINE DERIVATIVES
NO792502A NO792502L (en) 1978-08-01 1979-07-30 PROCEDURE FOR THE PREPARATION OF PHENYL PIPERAZINE DERIVATIVES
IL57920A IL57920A0 (en) 1978-08-01 1979-07-30 1-phenylpiperazine derivatives,their preparation and pharmaceutical compositions containing them
DK321479A DK321479A (en) 1978-08-01 1979-07-30 PROCEDURE FOR THE PREPARATION OF 1-PHENYL PIPERAZINE DERIVATIVES
LU81562A LU81562A1 (en) 1978-08-01 1979-07-30 PHENYL-1 PIPERAZINE DERIVATIVES
BE0/196538A BE877994A (en) 1978-08-01 1979-07-31 PHENYL-1 PIPERAZINE DERIVATIVES
ES483003A ES483003A1 (en) 1978-08-01 1979-07-31 1-Phenylpiperazine derivatives
SE7906507A SE7906507L (en) 1978-08-01 1979-07-31 Phenyl-1-piperazine derivatives
JP9858679A JPS5522690A (en) 1978-08-01 1979-07-31 11phenylpiperazine derivative and its manufacture
PT70007A PT70007A (en) 1978-08-01 1979-07-31 PROCESS FOR THE PREPARATION OF PHENYL-1 PIPERAZINE DERIVATIVES
FI792401A FI792401A (en) 1978-08-01 1979-08-01 1-PHENYL-PIPERAZINDERIVAT
GR59710A GR69703B (en) 1978-08-01 1980-07-27

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR7822672A FR2432515A1 (en) 1978-08-01 1978-08-01 CNS-active 1-phenyl-piperazine cpds. - useful as analgesics and psychotropic agents
FR7833105A FR2442234A2 (en) 1978-08-01 1978-11-23 CNS-active 1-phenyl-piperazine cpds. - useful as analgesics and psychotropic agents
FR7916029A FR2459797A2 (en) 1978-08-01 1979-06-22 PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION

Publications (2)

Publication Number Publication Date
FR2459797A2 true FR2459797A2 (en) 1981-01-16
FR2459797B2 FR2459797B2 (en) 1982-05-14

Family

ID=27250847

Family Applications (1)

Application Number Title Priority Date Filing Date
FR7916029A Granted FR2459797A2 (en) 1978-08-01 1979-06-22 PHENYL-1 PIPERAZINE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION

Country Status (18)

Country Link
JP (1) JPS5522690A (en)
AU (1) AU4930979A (en)
BE (1) BE877994A (en)
DE (1) DE2930440A1 (en)
DK (1) DK321479A (en)
ES (1) ES483003A1 (en)
FI (1) FI792401A (en)
FR (1) FR2459797A2 (en)
GB (1) GB2027703A (en)
GR (1) GR69703B (en)
IL (1) IL57920A0 (en)
IT (1) IT1123497B (en)
LU (1) LU81562A1 (en)
NL (1) NL7905810A (en)
NO (1) NO792502L (en)
NZ (1) NZ191140A (en)
PT (1) PT70007A (en)
SE (1) SE7906507L (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2582288B1 (en) * 1985-05-21 1987-08-07 Massonnet Henry IMPROVED COMPACT BIN
SE9904723D0 (en) * 1999-12-22 1999-12-22 Carlsson A Research Ab New modulators of dopamine neurotransmission II
USRE46117E1 (en) 1999-12-22 2016-08-23 Teva Pharmaceuticals International Gmbh Modulators of dopamine neurotransmission
SE9904724D0 (en) 1999-12-22 1999-12-22 Carlsson A Research Ab New modulators of dopamine neurotransmission I
WO2005121087A1 (en) 2004-06-08 2005-12-22 A. Carlsson Research Ab New disubstituted phenylpiperidines/piperazines as modulators of dopamine neurotransmission
US7851629B2 (en) 2004-06-08 2010-12-14 Nsab, Filial Af Neurosearch Sweden Ab, Sverige Disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission
MXPA06013941A (en) 2004-06-08 2007-12-10 Neurosearch Sweden Ab New disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission.
NZ555094A (en) 2004-10-13 2009-07-31 Nsab Af Neurosearch Sweden Ab Process for the synthesis of 4-(3-methanesulfonylphenyl)-1-n-propyl-piperidine
SE529246C2 (en) 2005-10-13 2007-06-12 Neurosearch Sweden Ab New disubstituted phenyl-piperidines as modulators of dopamine neurotransmission
TWI579272B (en) 2011-12-08 2017-04-21 梯瓦製藥國際有限責任公司 The hydrobromide salt of pridopidine

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2976290A (en) * 1959-04-24 1961-03-21 Parke Davis & Co Piperazine derivatives and methods for their production
CH353743A (en) * 1955-06-29 1961-04-30 Parke Davis & Co Method for preparing piperazines
FR2224464A1 (en) * 1973-04-05 1974-10-31 Synthelabo N-Phenyl-N'-beta-hydroxy-ethyl piperazines - as analgesic and anti-inflammatory agents

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH353743A (en) * 1955-06-29 1961-04-30 Parke Davis & Co Method for preparing piperazines
US2976290A (en) * 1959-04-24 1961-03-21 Parke Davis & Co Piperazine derivatives and methods for their production
FR2224464A1 (en) * 1973-04-05 1974-10-31 Synthelabo N-Phenyl-N'-beta-hydroxy-ethyl piperazines - as analgesic and anti-inflammatory agents

Also Published As

Publication number Publication date
IT7924749A0 (en) 1979-07-27
GR69703B (en) 1982-07-09
NL7905810A (en) 1980-02-05
IL57920A0 (en) 1979-11-30
FR2459797B2 (en) 1982-05-14
DE2930440A1 (en) 1980-02-28
NO792502L (en) 1980-02-04
ES483003A1 (en) 1980-04-16
JPS5522690A (en) 1980-02-18
DK321479A (en) 1980-02-02
SE7906507L (en) 1980-02-02
BE877994A (en) 1980-01-31
IT1123497B (en) 1986-04-30
NZ191140A (en) 1981-01-23
PT70007A (en) 1979-08-01
AU4930979A (en) 1980-02-07
GB2027703A (en) 1980-02-27
FI792401A (en) 1980-02-02
LU81562A1 (en) 1981-03-24

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