DK143903B - Analogifremgangsmaade til fremstilling af 1,3-dihydro-3-phenyl-1!-(2-propynyl) spiro (isobenzofuran-1,4!-piperidin) eller syreadditionssalte deraf - Google Patents
Analogifremgangsmaade til fremstilling af 1,3-dihydro-3-phenyl-1!-(2-propynyl) spiro (isobenzofuran-1,4!-piperidin) eller syreadditionssalte deraf Download PDFInfo
- Publication number
- DK143903B DK143903B DK318976AA DK318976A DK143903B DK 143903 B DK143903 B DK 143903B DK 318976A A DK318976A A DK 318976AA DK 318976 A DK318976 A DK 318976A DK 143903 B DK143903 B DK 143903B
- Authority
- DK
- Denmark
- Prior art keywords
- isobenzofuran
- piperidine
- dihydro
- propynyl
- acid addition
- Prior art date
Links
- 239000002253 acid Substances 0.000 title description 11
- 150000003839 salts Chemical class 0.000 title description 8
- -1 2-PROPYNYL Chemical class 0.000 title description 7
- 238000000034 method Methods 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 description 13
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 1
- VTQBSZIFLYEXBK-UHFFFAOYSA-N 1'-prop-2-ynylspiro[1H-2-benzofuran-3,4'-piperidine] Chemical compound C(C#C)N1CCC2(CC1)OCC1=CC=CC=C12 VTQBSZIFLYEXBK-UHFFFAOYSA-N 0.000 description 1
- YSUMOYKBXHKNMK-UHFFFAOYSA-N 1-phenyl-1'-prop-2-ynylspiro[1h-2-benzofuran-3,4'-piperidine] Chemical compound C1CN(CC#C)CCC21C1=CC=CC=C1C(C=1C=CC=CC=1)O2 YSUMOYKBXHKNMK-UHFFFAOYSA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 description 1
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
- GHBSKQGCIYSCNS-NAKRPEOUSA-N Ala-Leu-Asp-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O GHBSKQGCIYSCNS-NAKRPEOUSA-N 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 101100108536 Rattus norvegicus Aldh3a1 gene Proteins 0.000 description 1
- ADSXDBCZNVXTRD-UHFFFAOYSA-N [Mg]C1=CC=CC=C1 Chemical compound [Mg]C1=CC=CC=C1 ADSXDBCZNVXTRD-UHFFFAOYSA-N 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
- 208000017502 proteosome-associated autoinflammatory syndrome Diseases 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 229960005333 tetrabenazine Drugs 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
o 1 143903
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af den hidtil ukendte 1,3-dihydro--3-phenyl-l(2-propynyl)spiro[isobenzofuran-1,4'-piperidin] eller farmaceutisk acceptable syreadditionssalte deraf, hvilke 5 forbindelser er anvendelige som antidepressionsmidler.
1' -Alkyl-1,3-dihydro-3-phenylspiro [ isobenzofuran-1, 4' --piperidin]-forbindelser findes beskrevet i dansk patentansøgning nr. 6449/74, men fremstillingen af disse forbindelser er ikke omfattet af nærværende opfindelse.
10 Den her omhandlede forbindelse, som adskiller sig fra de nævnte kendte ved at have en 2-propynyl-gruppe i 1·-stillingen i stedet for en alkyl-gruppe, er endvidere, som det fremgår nedenfor, de kendte forbindelser overlegne med hensyn til antidepres sant-egenskaber.
25 Den her omhandlede, hidtil ukendte 1,3-dihydro-3- -phenyl-1'-(2-propynyl)spiro[isobenzofuran-1,4'-piperidin] er af formlen
CH2C=CH
20 (CH2/V2^ J^H2*2 (I)
25 H
og opfindelsen omfatter også fremstillingen af de farmaceutisk acceptable syreadditionssalte deraf.
Syrer, der er anvendelige til fremstilling af de 20 farmaceutisk acceptable syreadditionssalte, omfatter uorganiske syrer, såsom saltsyre, hydrogenbromid, svovlsyre, salpetersyre, phosphorsyre og perchlorsyre, såvel som organiske syrer såsom vinsyre, citronsyre, eddikesyre, ravsyre, maleinsyre, fumar-syre og oxalsyre.
35 Analogifremgangsmåden ifølge opfindelsen til frem stilling af forbindelsen af formlen I eller de farmaceutisk 2 143903 o acceptable syreadditionssalte deraf er kendetegnet ved, at 1,3-dihydro-3-phenylspiro[isobenzofuran-1,41-piperidin] af formlen
H
5 <CH2}2 £^2*2 (II
0$
10 H
25 omsættes med et propargylhalogenid eller en propargylsulfon- syreester, hvorefter den opnåede forbindelse, om ønsket, omdannes til et farmaceutisk acceptabelt syreadditionssalt.
Omsætningen udføres fortrinsvis i nærværelse af et organisk opløsningsmiddel og en syreoptager ved en temperatur 20 mellem omgivelsernes og tilbagesvalingstemperaturen for reaktionsblandingen .
Den som udgangsmateriale anvendte forbindelse af formlen II findes beskrevet i den ovenfor nævnte patentansøgning nr. 6449/74, ifølge hvilken den fremstilles på følgende 25 måde: En o-halogenbenzoesyre omdannes til det tilsvarende benzoylchlorid ved behandling med et halogeneringsmiddel, hvorefter den fremkomne forbindelse omsættes med 2-aminoethanol til dannelse af et tilsvarende o-halogen-N-(1-hydroxyethyl)--benzamid, som cycliseres ved behandling med et dehydratise-20 ringsmiddel, f.eks. thionylchlorid, til dannelse af en tilsvarende o-halogenphenyloxazolin. Denne oxazolin omdannes derefter under sædvanlige betingelser til et tilsvarende Grignard-rea-gens, som omsættes med piperidin-4-on til dannelse af en tilsvarende oxazolinylphenyl-hydroxypiperidin, som be-25 handles med vandig saltsyre eller svovlsyre til dannelse af en tilsvarende 1,3-dihydrospiro[isobenzofuran-piperidin]-3-on.
0 3 143903
Denne forbindelse omsættes derefter med phenylmagnesium-lialogenid eller med phenyllithium til dannelse af en tilsvarende 1,3-dihydro-3-hydroxy-3-phenylspiro[isobenzofuran--piperidin], som reduceres til en tilsvarende o-hydroxyalkyl-5 -phenylhydroxypiperidin. Denne alkanol cycliseres til dannelse af en tilsvarende substitueret 1,3-dihydrospiro[isobenzofuran--piperidin] under anvendelse af en syre, og denne forbindelse er udgangsforbindelse for fremgangsmåden ifølge opfindelsen.
Ved den foretrukne udførelsesform anvendes der 10 n-butanol som opløsningsmiddel og kaliuracarbonat som syreop tager ved en temperatur netop under tilbagesvalingstemperaturen.
De hidtil ukendte forbindelser af formlen I er som nævnt anvendelige til behandling af depressioner hos pattedyr, 15 hvilket er påvist gennem deres evne til at hamme tetrabenazin- -induceret depression hos mus (International Journal of Neuropharmacology, 8, 73, 1969), en prøve, der er anerkendt som standardprøve for antidepressant-egenskaber. Ved denne prøve har 1,3-dihydro-3-pheny1-1'-(2-propynyl)spiro[iso-20 benzofuran-l,4'-piperidin] bevirket,en 50%'s hæmning af ptosis ved benazin-induceret depression i en intraperitoneal dosis på 1,3 mg pr. kg legemsvægt.
Ved samme prøve har de nært beslægtede 1'-methyl-, 1'-ethyl- og l'-butyl-l,3-dihydro-3-phenylspiro[isobenzofuran-25 -1,4'-piperidin]-forbindelser, der er omhandlet i dansk pa tentansøgning nr. 6449/74, vist en mindste effektiv dosis (MED) på henholdsvis 1,0, 5,0 og 10,0 mg/kg, og det må her erindres, at MED-værdien altid vil være meget mindre end EDsQ-værdien, hvorfor MED-værdien for den ovenfor nævnte 30 1'-(2-propynyl)-forbindelse med en EDgg-værdi på 1,3 mg/kg vil være meget mindre end for de tidligere beskrevne 1'-alkyl--forbindelser.
Endvidere udviser forbindelsen af formlen I lave toksicitetsværdier, idet den ved forsøg med mus i 35 grupper på fire under anvendelse af forskellige doser og notering af antallet af dødsfald har vist en ALD^-værdi (dvs. den akutte letale intraperitoneale dosis, i mg pr. kg. legemsvægt, for 50% af forsøgsmusene) på 562 mg/kg.
o 4 143903
Forbindelsen af formlen I kan til behandling af depressioner indgives i mængder fra ca. 1 til ca. 50 mg pr. kg legemsvægt pr. dag på forskellig måde, f.eks. oralt i kapsler eller tabletter, parenteralt i form af sterile opløsninger 5 eller suspensioner og i nogle tilfælde intravenøst i form af sterile opløsninger. De frie baser er effektive i sig selv, men de indgives fortrinsvis i form af deres farmaceutisk acceptable syreadditionssalte på grund af disses stabilitet, krystaliisationslethed og forøgede opløselighed.
10 Det følgende eksempel skal tjene til nærmere illu strering af fremgangsmåden ifølge opfindelsen.
Eksempel
Til en opløsning af 3,0 g l,3-dihydro-3-phenylspiro-[isobenzofuran-l,4'-piperidin] og 10,0 g kaliumcarbonat i 15 100 ml n-hutanol sættes 1,0 ml propargylchlorid, og blandingen opvarmes under omrøring til næsten tilbagesvalingstemperaturen for opløsningen (qa. 115°C), hvor den holdes i 26 timer.
Derefter filtreres blandingen ved. 90°C til fjernelse af uorganiske salte, og filtratet giver efter køling krystaller, som 20 fjernes ved filtrering, vaskes med n-butanol og omkrystalliseres fra ethanol, hvorved der fås farveløse nåle af 1,3--dihydro-3-phenyl-r'-(2-propynyl)spiro[isobenzofuran-1,4'--piperidin] med smp. 146-147°C.
Analyse, ber.f. C2iH21NO: C = 83,13%, H = 6,98%, N = 4,62% 25 fundet: C = 83,01%, H = 7,12%, N = 4,51%.
30 35
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59616375 | 1975-07-15 | ||
| US05/596,163 US3980786A (en) | 1975-07-15 | 1975-07-15 | 1,3-Dihydro-3-phenyl-1'-(2-propynyl)spiro[isobenzofuran]s |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK318976A DK318976A (da) | 1977-01-16 |
| DK143903B true DK143903B (da) | 1981-10-26 |
| DK143903C DK143903C (da) | 1982-04-13 |
Family
ID=24386208
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK318976A DK143903C (da) | 1975-07-15 | 1976-07-14 | Analogifremgangsmaade til fremstilling af 1,3-dihydro-3-phenyl-1'-(2-propynyl)spiro(isobenzofuran-1,4'-piperidin)eller syreadditionssalte deraf |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US3980786A (da) |
| JP (1) | JPS5210264A (da) |
| AT (1) | AT355568B (da) |
| BE (1) | BE844158A (da) |
| CA (1) | CA1088529A (da) |
| CH (1) | CH621553A5 (da) |
| DE (1) | DE2629570A1 (da) |
| DK (1) | DK143903C (da) |
| FR (1) | FR2317923A1 (da) |
| GB (1) | GB1549887A (da) |
| IE (1) | IE43276B1 (da) |
| IT (1) | IT1065962B (da) |
| LU (1) | LU75382A1 (da) |
| NL (1) | NL7607625A (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4409229A (en) * | 1977-12-02 | 1983-10-11 | Hoechst-Roussel Pharmaceuticals, Inc. | Antidepressive and tranquilizing substituted 1,3-dihydrospiro[benzo(c)thiophene]s |
| JPS56122747A (en) * | 1980-02-27 | 1981-09-26 | Ricoh Co Ltd | Corrector for skew and lateral position of paper |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3635956A (en) * | 1968-03-01 | 1972-01-18 | Squibb & Sons Inc | Benzothiazines related compounds derivatives and salts thereof |
| US3686186A (en) * | 1970-10-05 | 1972-08-22 | William J Houlihan | Substituted isochroman or phthalan piperidenes |
| US3959475A (en) * | 1973-12-12 | 1976-05-25 | American Hoechst Corporation | Substituted 1,3-dihydrospiro(isobenzofuran)s |
-
1975
- 1975-07-15 US US05/596,163 patent/US3980786A/en not_active Expired - Lifetime
-
1976
- 1976-06-10 GB GB24058/76A patent/GB1549887A/en not_active Expired
- 1976-07-01 DE DE19762629570 patent/DE2629570A1/de not_active Withdrawn
- 1976-07-09 NL NL7607625A patent/NL7607625A/xx not_active Application Discontinuation
- 1976-07-12 CH CH892076A patent/CH621553A5/de not_active IP Right Cessation
- 1976-07-13 IT IT25273/76A patent/IT1065962B/it active
- 1976-07-14 AT AT517376A patent/AT355568B/de not_active IP Right Cessation
- 1976-07-14 CA CA256,934A patent/CA1088529A/en not_active Expired
- 1976-07-14 IE IE1551/76A patent/IE43276B1/en unknown
- 1976-07-14 DK DK318976A patent/DK143903C/da not_active IP Right Cessation
- 1976-07-14 LU LU75382A patent/LU75382A1/xx unknown
- 1976-07-15 BE BE168938A patent/BE844158A/xx unknown
- 1976-07-15 JP JP51083583A patent/JPS5210264A/ja active Pending
- 1976-07-15 FR FR7621620A patent/FR2317923A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| ATA517376A (de) | 1979-08-15 |
| JPS5210264A (en) | 1977-01-26 |
| NL7607625A (nl) | 1977-01-18 |
| BE844158A (fr) | 1977-01-17 |
| CH621553A5 (da) | 1981-02-13 |
| AT355568B (de) | 1980-03-10 |
| IT1065962B (it) | 1985-03-04 |
| FR2317923B1 (da) | 1978-12-15 |
| DE2629570A1 (de) | 1977-02-03 |
| IE43276L (en) | 1977-01-15 |
| LU75382A1 (da) | 1977-04-04 |
| IE43276B1 (en) | 1981-01-28 |
| CA1088529A (en) | 1980-10-28 |
| GB1549887A (en) | 1979-08-08 |
| DK143903C (da) | 1982-04-13 |
| DK318976A (da) | 1977-01-16 |
| FR2317923A1 (fr) | 1977-02-11 |
| US3980786A (en) | 1976-09-14 |
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