IL31660A - Thiepine derivatives,their preparation and pharmaceutical compositions containing them - Google Patents
Thiepine derivatives,their preparation and pharmaceutical compositions containing themInfo
- Publication number
- IL31660A IL31660A IL31660A IL3166069A IL31660A IL 31660 A IL31660 A IL 31660A IL 31660 A IL31660 A IL 31660A IL 3166069 A IL3166069 A IL 3166069A IL 31660 A IL31660 A IL 31660A
- Authority
- IL
- Israel
- Prior art keywords
- thiepin
- dihydro
- dibenzo
- methoxy
- acid
- Prior art date
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Description
»*i*t- m Tnian ,niwm 9«»n nn>m
New thiepinftderivatlves, their preparation and pharmaceutical compositions containing them
CIBA-GEIGI A.G.
C. 29818
J. R. GEIGY A.G. BAS EL 21
4-2943*
gpnrv Q -γ^ RQB¾&-£LQ n MFTJ THTKPT DERIVATIVES
The present invention concerns new thiepin derivatives, a process for the production thereof, medicaments
containing the new compounds and their use.
Thiepin derivatives of the general formula I
CH^ - CH,
\
wherein
X represents the methoxy or methylthio group,
as well as their addition salts with inorganic or organic acids have not been known hitherto .
It has now been found that these compounds as well as their salts have valuable pharmacological properties and a high therapeutic index. In the case of oral, rectal or parenteral administration they have a central depressant action, e.g. they reduce motility, potentiate the narcosis and exhibit a positive action in the "test de la traction". Furthermore, they also have an antiemetic action.
31660/2
2
In comparison with the stated central depressant properties, their cataleptic inherent effect is small. These properties, which are determined by selected standard test methods
[cp. R. Domenjoz and W. Theobald, Arch.- Int. Pharmacodyn . 120, ,450 (1959), and W.Theobald ' et al . , Arzneimittelforsch . 17, 561 (1967) ] , characterise the compounds as being suitable for the treatment of states of tension and agitation.
British Patent Specification o. 1,093,910 discloses certain 10-(l-piperazinyl)~10,ll-dihydro-dibenzo[b,f]thiepines which
differ from the compound of formula I according to this invention, in that instead of the 8-methoxy or 8-methylthio group in formula I, those known compounds bear a halo substituent on one or on each of the benzene rings. The known compounds have' activities on the central nervous system, but they are inferior in this-"respect
■7 ' to the compounds of this invention, as shown by the comparative pharmacological tests described in Example 5 herein.
A compound of the general formula I is produced according
to the invention by hydrol sing or hydrogenolysing a compound
of the general
wherein ,
X has the meaning given under formula I and
Y represents a radical, which can be replaced by hydrogen
by means of hydrolysis or reductive splitting, and .
optionally converting the obtained reaction product with
an inorganic or organic acid into an addition salt. t
Radicals Y, which can be converted by hydrolysis into the
hydrogen atom are, e.g. acyl radicals,, e.g.1 lower alkanoyl
groups such as the acetyl group, aryl-carbonyl groups such as
the benzoyl group, radicals of monofunctional derivatives . of
earboxylic acid or thiocarboxylic acid such aa, e.g. the
In comparison with the stated central depressant properties, their cataleptic inherent effect is small. These properties, which are determined by selected standard test methods
[cp. R. Domenjoz and W . Theobald, Arch. Int. Pharmacodyn . 120 , 450 (1959), and W.Theobald et al . , Arzneimittelforsch . JL7, 561
(1967) ] , characterise the compounds as being suitable for the treatment of states of tension and agitation.
A compound of the general formula I is produced according to the invention by hydrolysing or hydrogenolysing a compound of the general formula II
wherein
X has the meaning given under formula I and
Y represents a radical, which can be replaced by hydrogen by means of hydrolysis or reductive splitting, and
optionally converting the obtained reaction product with an inorganic or organic acid into an addition salt.
Radicals Y, which can be converted by hydrolysis into the hydrogen atom are, e.g. acyl radicals, e.g. lower alkanoyl groups such as the acetyl group, aryl-carbonyl groups such as the benzoyl group, radicals of onofunctional derivatives of
methoxycarbonyl , ethoxycarbonyl , phenoxycarbony1 or the benzyloxycarbonyl group, or the corresponding thiocarbonyl groups. The hydrolysis can be performed using an alkali metal hydroxide, e.g. potassium or sodium hydroxide, preferably at boiling temperature and either in a higher-boiling
organic solvent, which contains hydroxyl groups such as, e.g. ethylene glycol or diethylene glycol, or in a lower monoalkyl ether of a suchlike glycol and, in particular, in a lower alkanol , e.g. methanol or ethanol .
Radicals Y, which are convertable by reductive splitting into the hydrogen atom, are, for example, arylmethyl groups, such as the benzyl group, diarylmethyl groups such as the diphenylmethyl group, or arylmethoxycarbonyl groups such as the benzyloxycarbonyl group . The reductive splitting can be carried out with hydrogen in an inert solvent in the presence of a sulphide^^oble metal/ catalyst on a
suitable carrier, e.g. in a lower alkanol, such as
methanol or ethanol, in the presence of
or platinum on coal .
Starting materials of the general formula II can be
produced, for example, starting with 8-methoxy- or 8-methyl-thio-10-chloro-10,ll-dihydro-dibenzo [b,f ]thiepin known in the literature . These compounds are reacted for example with 1-piperazine carboxylic acid esters, e.g. with the methyl, ethyl, phenyl or benzyl ester, to give the corresponding esters of the 4- (8-methoxy-10, 11-dihydro-dibenzo [b, f ] -thiepin-10-yl)-l-piperazine carboxylic acid or the
4- (8-methyl hio- 10 , 11- dihydro-dibenzo [b , f ] hiepin- 10-yl) - 1-piperazine carboxylic acid. The corresponding thiocarboxylic acid esters can be produced analogously. Compounds of the general formula II, which are substituted in 4-position of the piperazine ring for example by a lower alkanoyl group, e.g. the acetyl group, by an arylcarbonyl group, e.g. the benzoyl group, or by an arylmethyl group, e.g. the benzyl group, can be analogously produced, e.g. by reacting the 8-methoxy- or the 8-methylthio-10-chloro-10,ll-dihydro-dibenzo [b , f ] thiepin , with the corresponding piperazine derivatives, e.g. with the 1- acetyl, 1-benzoyl or the
1-benzyl piperazine .
The compounds of the general formula I obtained
using the process according to the invention, are then optionally converted, in the usual manner, into their addition salts with inorganic and organic acids . For
example, a solution of a compound of the general formula I in an organic solvent is mixed with the acid desired
as the salt component, or with a solution of the acid.
For the reaction, organic solvents are preferably chosen, in which the formed salt has low solubility, so that it can be separated by filtration. Such solvents are, e.g.
methanol, acetone, methyl-ethyl ketone, acetone /ethanol , methanol /ether or ethanol /ether .
For use as medicaments, pharmaceutically acceptable acid addition salts can be used in place of free bases,
toxic in the case of the dosages in question. It is
moreover of advantage if the salts to be used as medicaments crystallise well and are not, or only slightly,
hygroscopic. For salt formation with compounds of the general formula I, it is possible to use, e.g. hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methane sulphonic acid, ethane sulphonic acid,
β-hydroxyethane sulphonic acid, acetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenyl acetic acid, mandelic acid and embonic acid.
As mentioned above, the new active substances are
administered orally, rectally or parenterally . The dosage depends on the manner of administration of the medicaments, on the age and on the individual condition . The daily dosages of the free bases or of pharmaceutically acceptable salts thereof, vary between 0.10 mg/kg and 10.5 mg/kg for warm blooded animals. Suitable dosage units,
such as dragees, tablets, suppositories or ampoules,
preferably contain 5-200 mg of an active substance
according to the invention, or of a pharmaceutically
acceptable salt thereof.
Dosage units for oral administration preferably
contain as active substance between 1-90% of a compound of the general formula I or of a pharmaceutically
acceptable salt thereof. They are produced by combining
the active substance with, e.g. solid, pulverulent
carriers such as lactose, saccharose, sorbitol, mannitol; starches such as potato starch, maize starch or amylopectin, also laminaria powder or citrus pulp powder; cellulose derivatives or gelatine, optionally with the addition of lubricants, such as magnesium or calcium stearate
or polyethylene glycols, to form tablets or dragfee cores. The latter are coated, e.g. with concentrated sugar
solutions, which can also contain, e.g. gum arabic,
talcum and/or titanium dioxide, or with a lacquer
dissolved in easily volatile organic solvents or mixtures of solvents. Dyestuffs can be added to these coatings, e.g. to distinguish between varying dosages of active substance .
Other suitable dosage units for oral administration are hard capsules made of gelatine as well as soft, closed capsules made of gelatine and a softener such as glycerin. The hard capsules preferably contain the active substance as a granulate, e.g. in admixture with fillers such
as maize starch, and/or lubricants such as talcum or
magnesium stearate and, optionally, stabilisers, such as sodium metabisulphite or ascorbic acid. In
soft capsules, the active substance is preferably dissolved or suspended in suitable liquids such as liquid
polyethylene glycols, to which stabilisers can also
be added .
Suitable dosage units for rectal administration are for example suppositories, which consist of a combination of an active substance or of a suitable salt thereof with a suppository foundation. Suitable as the suppository foun tion are, e.g. natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene glycols or higher alkanols. Gelatine rectal capsules are also suitable, which consist of a combination of an active substance or of a suitable salt thereof and a foundation. Examples of the foundation are, e.g. liquid triglycerides, polyethylene glycols or paraffin hydrocarbons .
Ampoules for parenteral, particularly intramuscular, administration preferably contain a water-soluble salt of an active substance in a concentration of preferably 0.5-5%, optionally together with suitable stabilisers and buffer substances, in an aqueous solution.
The following prescriptions further illustrate the production of tablets, dragees, capsules, suppositories and ampoules :
a) 250 g of 8-methoxy-10- (l-piperazinyl)-10,ll-dihydro-dibenzo [b , f ] thiepin-dihydrochloride are mixed with 175.80 g of lactose and 169.70 g of potato starch. The mixture is moistened with an alcoholic solution of 10 g of stearic acid and granulated through a sieve.
After drying, 160 g of potato starch, 200 g of talcum, 2.5 g of magnesium stearate and 32 g of colloidal silicon
dioxide are mixed in and the mixture is pressed into
,000 tablets, each weighing 100 mg and each containing
mg of active substance. Optionally, the tablets can be provided with grooves for more accurate adjustment of
the dosage amount .
b) A granulate is produced from 250 g of 8-methylthio-10- (1-piperazinyl) -10 , 11-dihydro-dibenzo [b , f ] thiepin-hydrochlor-ide, 175.90 g of lactose and the alcoholic solution of 10 g of stearic acid. After drying, the granulate is mixed with
56.60 g of colloidal silicon dioxide, 165 g of talcum,
g of potato starch and 2.50 g of magnesium stearate
and the mixture is pressed into 10,000 dragee cores. These are subsequently coated with a concentrated syrup made from
502.28 g of crystallised saccharose, 6 g of shellac,
g of gum arabic, 0.22 g of dyestuff and 1.5 g of
titanium dioxide, and dried. The obtained dragees each
weigh 120 mg and each contain 25 mg of active substance .
c) To produce 1000 capsules each containing 25 mg
of active substance, 25 g of 8-methoxy-10- (1-piperazinyl) -10, 11-dihydro-dibenzo [b,f ] thiepin-dihydrochloride are
mixed with 248.0 g of lactose. The mixture is evenly
moistened with an aqueous solution of 2.0 g of gelatine
and is granulated through a suitable sieve (e.g. Sieve
No. Ill, Ph.Helv. V). The granulate is mixed with 10.0 g
of died maize starch and 15.0 g of talcum. The mixture
is uniformly filled into 1000 hard gelatine capsules,
d) A suppository foundation is prepared from 2.5 g of 8-methylthio-10- (1-piperazinyl) -10 , 11-dihydro-dibenzo [b , f ] -thiepin-hydrochloride and 167.5 g of adeps solidus .
100 suppositories are filled from the mixture each
containing 25 mg of active substance.
e) A solution of 25 g of 8-methylthio-10- (1-piperazinyl) -10, 11-dihydro-dibenzo [b,f] thiepin-hydrochloride in one
litre of water is filled into 1000 ampoules and sterilised.
An ampoule containes a 2.5% solution of 25 mg of active
substance.
The following examples further illustrate the
production of the new compounds of the general formula I
and of intermediate products not described hitherto, but
they do not in any way limit the scope of the invention.
The temperatures are given in degrees Centigrade .
Example 1
a) 42.0 g of crude 4- (8-methylthio-lO, 11-dihydro-dibenzo [b,f ]thiepin-10-yl)-l-piperazine carboxylic acid ethyl ester are added to a solution of 64.0 g of potassium
hydroxide in 400 ml of absolute ethanol . The reaction
mixture is refluxed for 16 hours . The ethanol is then
distilled off from the mixture, the residue poured on
to ice water and the suspension extracted with ether/
methylene chloride (2:1). The organic extract is washed with water until the pH is adjusted to 8. The organic
solution is then dried over magnesium sulphate and
concentrated by evaporation in vacuo. The obtained crude product is taken up in 100 ml of absolute acetone,
mixed with ethereal hydrochloric acid and the precipitated hydrochloride is recrystallised from 96% ethanol /ether .
The obtained pure 8-methylthio-10- (l-piperazinyl)-lO, 11-dihydro-dibenzo [b , f ] thiepin-hydrochloride melts at
220-222°.
The 4-(8-methylthio-10,ll-dihydro-dibenzo [b , f ] thiepin-10-yl) -1-piperazine carboxylic acid ethyl ester, which is used as the starting material, is produced as follows:
b) 26.9 g (0.092 mol) of 8-methylthio-lO-chloro-lO, 11-dihydro-dibenzo [b,f] thiepin, M.P. 106-109° are dissolved in 60 ml af absolute benzene and 47.4 (0.3 mol) of
1-piperazine carboxylic acid ethyl ester are added. The reaction mixture is refluxed for 20 hours, poured on to 500 ml of ice water and extracted with 800 ml of a mixture of
washed six times with water, dried over magnesium sulphate and concentrated by evaporation . in vacuo. The obtained oily 4- (8-methylthio-10, 11-dihydro-dibenzo [b, f ] thiepin-10-yl) -1-piperazine carboxylic acid ethyl ester is used as the crude product.
Example 2
The 8-methoxy-10- (1-piperazinyl) -10 , 11-dihydro-dibenzo- [b,f] thiepin, M.P. 105-107°, is produced, analogously to Example 1 a) , from 94.3 g (0.236 mol) of
4- (8-methoxy-10 , 11-dihydro-dibenzo [b , f ] thiepin- 10-yl) -1-piperazine carboxylic acid ethyl ester, M.P. 100-102°. The free base is converted in acetone by means of ethereal hydrochloric acid into the dihydrochloride, which melts at 179-181° after being recrystallised from ethanol/ ethyl acetate.
The 4- (8-methoxy-10 , 11-dihydro-dibenzo [b , f ] thiepin-10-yl)-l-piperazine carboxylic acid ethyl ester, which is used as starting material, is produced analogously to Example 1 b) , from 8-methoxy-10-chloro-10 , 11-dihydro-dibenzo [b , f ] thiepin and 1-piperazine carboxylic acid ethyl ester.
Example 3
18.4 g (0.05 mol) of 8-methoxy-10- (4- acetyl-1-piperazinyl) -10 , 11-dihydro-dibenzo fb , f ] thiepin and
40.0 g (0.71 mol) of potassium .hydroxide are
dissolved in 200 ml of absolute ethanol and refluxed for 20 hours. After the addition of 200 ml of water, the ethanol is largely distilled off and the residue shaken out with benzene . The benzene phase is
washed with water, dried over magnesium sulphate
and concentrated by evaporating to dryness in vacuo . The residue is dissolved in acetone and the
dihydrochloride precipitated by addition of ethereal hydrochloric acid.. After recrystallisation from ethanol/ ethyl acetate, the 8-methoxy-10- (1-piperazinyl) -10 , 11-dihydro-dibenzo [b, f ] thiepin-dihydrochloride melts at 179-181° .
The 8-methoxy- 10- (4- acetyl- 1-piperazyl) - 10, 11-dihydro-dibenzo [b,f] thiepin, which is used as the starting material, is obtained by reacting
8-methoxy-10-chloro- 10, 11-dihydro-dibenzo [b , f ] thiepin with 1-acetyl-piperazine , M.P. 156-157° (from benzene/ petroleum ether) .
Example 4
a) 4.9 g (0.01 mol) of 8-methoxy-10- (4-benzyl- 1-piperazinyl) -10 , 11-dihydro-dibenzo [b , f ] thiepin-dihydrochloride are dissolved in 200 ml of ethanol
and, after the addition of 2 g of palladium charcoal
(5% palladium on active charcoal) the mixture is hydrogenated at 20° and under a hydrogen pressure of 1 - 2 atm . The absorption of hydrogen is finished after 8 hours . The
catalyst is filtered off, washed with hot ethanol and
the combined filtrates are concentrated by evaporation
to dryness . The obtained residue is shaken with benzene and 2N sodium hydroxide solution and the benzene solution is then extracted with 1-molar aqueous methane sulphonic acid
solution. The acid aqueous solution is made alkaline
with concentrated sodium hydroxide solution and
shaken out with ether /methylene chloride (2:1) . The
organic phase is then washed with water and dried over
magnesium sulphate. After removal of the solvent under
vacuum, the obtained base is dissolved in acetone and, by addition of ethereal hydrochloric acid, the
dihydrochloride is precipitated. The pure 8-methoxy- 10- (1-piperazinyl) -10 , 11-dihydro-dibenzo [b, f ]-thiepin-dihydrochloride , M.P. 179-181°, is obtained
after recrystallisation from ethanol/ethyl acetate.
The 8-methoxy-10- (4-benzyl-l-piperazinyl) -10 , 11-dihydro-dibenzo [b,f] thiepin, which is required as the
starting product, is produced as follows:
b) 18.0 g (0.12 mol) of 1-benzyl-piperazine are added dropwise to a solution of 7.0 g (0.0256 mol) of 8-methoxy-lO-chloro-10, 11-dihydro-dibenzo [b , f ] thiepin in 40 ml of absolute benzene . After being refluxed for 20 hours, the reaction mixture is poured on to 200 ml of ice water and, after addition of 25 ml of 2N sodium hydroxide solution, it is shaken out with benzene. The organic phase is repeatedly washed with water and then extracted with 60 ml of 1-molar aqueous methane sulphonic acid solution . The acid aqueous solution is made alkaline with concentrated sodium hydroxide solution and shaken out with
ether /methylene chloride (2:1). The organic extracts are then washed with water, dried over magnesium sulphate and the solvents are removed under vacuum. The residue is recrystallised from benzene/petroleum ether. The pure 8-methoxy- 10- (4-benzyl-l-piperazinyl)-10, 11-dihydro-dibenzo [b,f 3 hiepin melts at 118-120°. The dihydrochloride has a M.P. of 224-226° (from ethanol /ethyl acetate) .
The 8-methylthio-10- (4-benzyl-l-piperazinyl) -10 , 11-dihydro-dibenzo [b,f ] thiepin is produced in an analogous manner and from this is obtained the 8-methylthio-10- (1-piperazinyl) -10 , 11-dihydro-dibenzo [b , f ] thiepin-hydrochloride , M.P. 220-222°.
- 15a -
EXAMPLE 5
The following compounds according to the invention
A) 8-Methoxy-10-(l-piperaainyl)-10,11-dihydro-dibeneo[b, ]thiepine, and
B) 8-Methylthio-10-(l-piperazinyl)-10,ll-dinydro-diDeni5oC' tf]thier pine,
were compared with the compound
C) 8-Chloro-10~(l-piperazinyl)-10fll-^
which is within the scope of British Specification No, 1,093,910, in respect of their pharmacological activities in potentiating narcosis and reducin the orientation motility.
gES¾? PROCEDURES
1) Narcosis potentiation
The compounds to be tested were injected subcutaneously to male and female mice weighing from 17 to 25 g each, 30 minutes ! before the administration to the mice of 40 mg/kg l.p. of the narcotioally active 2-methoxy-4-allyl-phen0-syac ic acid Ν,Ν*· diethylamide. The duration of the side-position of the thus
treated animals was measured and compared with the duration of the side-position of control animals which had received only the
above mentioned naroo ioua, but none of the oompounds to be
tested* She change of the duration of the side-position in
comparison with the controls, is given in percents.
2) Or^erflal qn moW†,Y
Groups of mice, weighing from 18 to 21 g each, are
placed in plexiglass cages of 30 x 20 x 9 cm. A beam of light is
- 15b - passed through the cages, and its interruptions caused by the movement of the mice, are registered by means of a photocell and a counter* The animals are placed in the cages 30 minutes after they have been injected with the compounds to be tested. The motility is observed during 15 minutes and that doeie ia sought which causes a eduction of 50$ of the mean value as compared with the control animals (=»DE^0). The evaluation is carried out with the aid of the semi-logarithmic charts of Schleicher and Sohull, So. 3731/2,
RESULTS
Naroosla potentiation Orientation
Compound Dosls mg/kg Change in # motility
S.C. 1)Ε„ mg/kg i.p.
A 2 >+575# 0.72
>+671&
B 2 +1435* 0*74
3 ♦586#
C 2 *U% 0.9
+ 8695
CONCIffSIOflS
The test results of the narcosis potentiation show an up to abou 8-fold higher activity of the compounds according to the invention as compared to the known compound. In reapeot of the orientation motility, the compounds aocording to t he invention are at least 1*2 times more active than the known compound used for comparison.
Claims (7)
1. New thiepin derivatives of the general formula I wherein X represents the methoxy or methylthio group, as well as their addition salts with inorganic or organic acids .
2. 8-Methoxy-10- (1-piperazinyl) -10 , ll-dihydro-dibenzo [b,f ] thiepin and its addition salts with inorganic or organic acids .
3. 8-Methylthio-10- (1-piperazinyl) -10, 11-dihydro-dibenzo [b , f ] thiepin and its addition salts with inorganic or organic acids .
4. Process for the production of new thiepin derivatives of the general formula I wherein X represents the methoxy or methylthio group, as well as their addition salts with inorganic or organic acids, characterised by hydrolysing or hydrogenol sing a compound of the general formula II wherein X has the meaning given under formula I, and Y represents a radical, which can be replaced by hydrogen by means of hydrolysis or reductive splitting and, optionally, converting the obtained reaction product with an inorganic or organic acid into an addition salt .
5. New thiepin derivatives of general formula I, as defined in claim 1, substantially as herein described with reference to and as illustrated in any of the foregoing examples .
6. Process according to claim 4, substantially as herein described with reference to and as illustrated in any of the foregoing examples .
7. Pharmaceutical composition containing as active ingredient at least one compound of formula I, defined in claim 1, together with at least one pharmaceutically acceptable carrier. 3.1.69/FUH/dZ - -
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH252968A CH493558A (en) | 1968-02-21 | 1968-02-21 | Process for the preparation of new imidazolidinone derivatives |
CH962668A CH499542A (en) | 1968-02-21 | 1968-06-27 | Process for the preparation of new imidazolidinone derivatives |
CH1808568A CH501662A (en) | 1968-02-21 | 1968-12-04 | Process for the preparation of new thiepine derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
IL31660A0 IL31660A0 (en) | 1969-04-30 |
IL31660A true IL31660A (en) | 1972-11-28 |
Family
ID=27173757
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL31660A IL31660A (en) | 1968-02-21 | 1969-02-20 | Thiepine derivatives,their preparation and pharmaceutical compositions containing them |
Country Status (8)
Country | Link |
---|---|
JP (1) | JPS4810474B1 (en) |
AT (1) | AT284132B (en) |
BR (1) | BR6906480D0 (en) |
FI (1) | FI48193C (en) |
IE (1) | IE33005B1 (en) |
IL (1) | IL31660A (en) |
NO (1) | NO122424B (en) |
PL (1) | PL76038B1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS526657U (en) * | 1975-07-01 | 1977-01-18 | ||
JPS6150289U (en) * | 1984-09-06 | 1986-04-04 |
-
1969
- 1969-02-12 FI FI43669A patent/FI48193C/en active
- 1969-02-13 NO NO59469A patent/NO122424B/no unknown
- 1969-02-20 AT AT169769A patent/AT284132B/en not_active IP Right Cessation
- 1969-02-20 IL IL31660A patent/IL31660A/en unknown
- 1969-02-20 PL PL13184969A patent/PL76038B1/pl unknown
- 1969-02-20 IE IE22469A patent/IE33005B1/en unknown
- 1969-02-20 JP JP1223069A patent/JPS4810474B1/ja active Pending
- 1969-02-20 BR BR20648069A patent/BR6906480D0/en unknown
Also Published As
Publication number | Publication date |
---|---|
IE33005B1 (en) | 1974-02-20 |
JPS4810474B1 (en) | 1973-04-03 |
NO122424B (en) | 1971-06-28 |
IE33005L (en) | 1969-08-21 |
BR6906480D0 (en) | 1973-04-19 |
PL76038B1 (en) | 1975-02-28 |
AT284132B (en) | 1970-09-10 |
FI48193C (en) | 1974-07-10 |
IL31660A0 (en) | 1969-04-30 |
FI48193B (en) | 1974-04-01 |
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