NO154091B - Analogifremgangsmaate for fremstilling av terapeutisk aktive fenylaminoimidazolin-derivater. - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive fenylaminoimidazolin-derivater. Download PDFInfo
- Publication number
- NO154091B NO154091B NO803862A NO803862A NO154091B NO 154091 B NO154091 B NO 154091B NO 803862 A NO803862 A NO 803862A NO 803862 A NO803862 A NO 803862A NO 154091 B NO154091 B NO 154091B
- Authority
- NO
- Norway
- Prior art keywords
- acid
- preparation
- general formula
- derivatives
- phenylaminoimidazoline
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 3
- 230000001225 therapeutic effect Effects 0.000 title description 2
- SACAEVOKRBNXPN-UHFFFAOYSA-N n-phenyl-4,5-dihydroimidazol-1-amine Chemical class C1=NCCN1NC1=CC=CC=C1 SACAEVOKRBNXPN-UHFFFAOYSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- JCOPITWIWLFFPC-UHFFFAOYSA-N n-phenyl-4,5-dihydro-1h-imidazol-2-amine Chemical class N1CCN=C1NC1=CC=CC=C1 JCOPITWIWLFFPC-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 11
- 230000033001 locomotion Effects 0.000 abstract description 3
- 229940035676 analgesics Drugs 0.000 abstract 1
- 239000000730 antalgic agent Substances 0.000 abstract 1
- 230000000059 bradycardiac effect Effects 0.000 abstract 1
- 125000001246 bromo group Chemical group Br* 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- FUOHKPSBGLXIRL-UHFFFAOYSA-N 2-(chloromethyl)thiophene Chemical compound ClCC1=CC=CS1 FUOHKPSBGLXIRL-UHFFFAOYSA-N 0.000 description 1
- -1 2-bromo-6-fluoro-phenyl Chemical group 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- VJLADBUFZUFOCT-UHFFFAOYSA-N n-[2-fluoro-6-(trifluoromethyl)phenyl]-4,5-dihydro-1h-imidazol-2-amine Chemical compound FC1=CC=CC(C(F)(F)F)=C1NC1=NCCN1 VJLADBUFZUFOCT-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Denne oppfinnelse angår fremstillinq av nye substituerte 2-fenylamino-imidazolin-(2)-derivater med den generelle formel I
og deres fysiologisk forlikelige syreaddisjonssalter med verdifulle terapeutiske egenskaper.
I formel I betyr
R et bromatom eller en trifluormetylgrunpe.
Forbindelsene med formel I fremstilles ved omsetning av et 2-fenylimino-imidazolidin med den generelle formel II
hvor R har de ovenfor angitte bctydn i.nger, med et halogenid med den generelle formel III
hvor Hal betyr et klor-, brom- eller jodatom.
Omsetningen skjer ved oppvarmning av reaksjonskomponentene - fortrinnsvis i nærvær av et polart eller upolart opplrSsnings-middel - til temperaturer på 40-150 C.
De spesielle reaksjonsbetinnelser er i sterk qrad av-hengig av reaktiviteten av reaksjonskomponentene. Ved alkyleringen anbefales det å anvende halogenidet med den generelle formel III i overskudd og utføre omsetningen i nærvær av et syrebindende middel.
UtgangsforbindeIsene med formel II er kjent fra litteraturen (se f.eks. belgisk patent 623.305). Forbindelsene med formel III kan fremstilles ved halogenering av de til-svarende alkoholer.
De nye 2-fenylamino-imidazolin-(2)-derivater med den generelle formel III kan på vanlig måte overføres til sine fysiologisk forlikelige syreaddisjonssalter. Syrer som er egnet for saltdannelse, er f.eks. saltsyre, bromhydrogensyre, jodhydrogensyre, fluorhydroqensyre, svovelsyre, fosforsyre, salpetersyre, eddiksyre, propionsyrc, smørsyre, kapronsyre, valeriansyre, oksalsyre, malonsyre, ravsyre, eplesyre, benzoe-syre, p-hydroksybenzoesyre, p-aminobenzoesyre, ftalsyre, kanelsyre, salicylsyre, askorbinsyre, metansulfonsyre, 8-klorteofyllin o.l.
De nye forbindelser med den generelle formel I og deres syreaddisjonssalter har en sterk analgetisk virkning og er derfor egnet til behandling av smertetilstander. Forbindelsene med den generelle formel I og deres syreaddisjonssalter kan anvendes enteralt eller parenteralt. Doseringen ligger ved 0,1 til 80 mg, fortrinnsvis 1 til 30 mg.
Forbindelsene mod formel I og deres syreaddisjonssalter kan også anvendes sammen med andre typer aktive stoffer. Egnede galeniske ti J.beredelsesformer er f.eks. tabletter, kapsler, stikkpiller, oppløsninger eller pulvere, og for fremstilling av disse preparater kan man anvende de vanlig anvendte qaleniske hjelpestoffer, bæremidler, sprengmidler eller smøremidler eller stoffer som medfører en depotvirkning.
De følgende eksempler illustrerer oppfinnelsen ytterligere.
Eksempel 1
2-[ N-( 2- fluor- 6- brom- fenyl)- N-( tienyl- 2- metyl)- amino]- 2-imidazolin
7,74 g (0,03 mol) 2-[(2-brom-6-fluor-fenyl)imino]-
imidazolidin oppvarmes sammen med 5 g (125%) 2-klormetyl-
tiofen og 4,5 ml trietylamin i 60 ml tørr toluen i 6 timer under omrøring ved tilbakeløpstemperatur. Det dannede bunnfall avsuges og oppløses i ca. IN IIC1. Den saltsure oppløsning ekstraheres to ganger med eter (eterekstraktene kastes) og alkaliseres derefter med 5N NaOH. Det derved utskilte produkt avsuges, vaskes med vann og tørres.
Utbytte: 6,5 g (61,2?, av det teoretiske).
Smeltepunkt: 107-108°C.
<C>14<H>13BrFN3S <354'24>
E ksempel 2 2-[ N- ( 2- fluor- 6- trifluormety1- feny1)- N-( tieny1- 2- mety1)- amino]-2- imidazolin
Analogt med fremgangsmåten beskrevet i eksempel 1
ble, ved å gå ut fra 2-[(2-fluor-6-trifluormety1-feny1)-imino]-imidazolidin og 2-klormetyl-tiofen, den ovenfor angitte forbindelse fremstilt i et utbytte på 56,3% av det teoretiske. Sm.p. 110 til 111°C.
FARMAKOLOGISKE SAMMENLIGNINGSFORSØK
En forbindelse fremstilt ifølge oppfinnelsen ble sammen-lignet med 2-[N-(tienyl-2-metyl)-N-(2,6-dibromfenyl)-amino]-imidazolin-(2) som er kjent fra norsk patent 136,408, med hensyn til analgetisk og bevegelseshemmende virkning på mus. Under-søkelsen med hensyn til analgetisk virkning ble foretatt i henhold til vridningsprøven ifølge Ph. Linee, offentliggjort i J. Pharmacol. (Paris) 3,4 513 til 515 (1972). Den bevegelseshemmende virkning ble utført i henhold til forskriften av K. Stockhaus og J.E. Villareal, , Committee on Problems of Drug Dependence (1970) 6890 til 6898, National Academy of Sciences:
Forbindelsen fremstilt ifølge oppfinnelsen er med hensyn til
sin smertestillende virkning dobbelt så sterk som det kjente sammenlignbare derivat. Den bevegelseshemmende virkning er for 2-fluor-6-brom-derivatet til og med 4 ganger sterkere enn for sammenligningsforbindelsen.
Claims (1)
- Analogifremgangsmåte for fremstillinq av terapeutisk aktive, substituerte 2-fenylamino-imidazoliner med den generelle formelhvor R betyr et bromatom eller en trLfluormetylgruppe, og syreaddisjonssalter derav, karakterisert ved at et 2-fenylimino-imidazolidin med den generelle formel IIhvor R har de ovenfor angitte bctydn i.nuer, omsettas med et halogenid med den generelle formel IIIhvor Hal betyr et klor-, brom- eller jodatom,og eventuelt overføres det erholdte sluttprodukt til et syreaddisjonssalt.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792951601 DE2951601A1 (de) | 1979-12-21 | 1979-12-21 | Neue substituierte 2-phenylaminoimidazoline-(2), deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zur herstellung derselben |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO803862L NO803862L (no) | 1981-06-22 |
| NO154091B true NO154091B (no) | 1986-04-07 |
| NO154091C NO154091C (no) | 1986-07-16 |
Family
ID=6089187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO803862A NO154091C (no) | 1979-12-21 | 1980-12-18 | Analogifremgangsmaate for fremstilling av terapeutisk aktive fenylaminoimidazolin-derivater. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4478844A (no) |
| EP (1) | EP0031429B1 (no) |
| JP (1) | JPS5697284A (no) |
| AT (1) | ATE8260T1 (no) |
| AU (1) | AU538931B2 (no) |
| CA (1) | CA1143738A (no) |
| DE (2) | DE2951601A1 (no) |
| DK (1) | DK544980A (no) |
| ES (1) | ES8202554A1 (no) |
| FI (1) | FI63940C (no) |
| IE (1) | IE50588B1 (no) |
| IL (1) | IL61769A (no) |
| NO (1) | NO154091C (no) |
| NZ (1) | NZ195897A (no) |
| ZA (1) | ZA807905B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT376436B (de) * | 1982-11-05 | 1984-11-26 | Laevosan Gmbh & Co Kg | Verfahren zur herstellung neuer thiophen-2carbons[urederivate und pharmazeutisch vertraeglicher saeure- oder basenadditionssalze davon |
| EP0200947B1 (de) * | 1985-04-26 | 1990-09-12 | F. Hoffmann-La Roche Ag | 1,3-Disubstituierte Imidazoliumsalze |
| US4740230A (en) * | 1985-09-13 | 1988-04-26 | Idemitsu Kosan Company Limited | Triazine derivatives, and herbicides containing the derivatives as the effective component |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2208434C2 (de) * | 1972-02-23 | 1982-09-16 | C.H. Boehringer Sohn, 6507 Ingelheim | Substituierte 2-(N-Furylmethyl-N-phenyl-amino)-2-imidazoline, deren Säureadditionssalze, Verfahren zu ihrer Herstellung und diese enthaltende Mittel |
| US4036972A (en) * | 1973-02-23 | 1977-07-19 | Boehringer Ingelheim Gmbh | 2-(N-thienylmethyl-phenylamino)-imidazolines-(2) and salts thereof |
| DE2308883C3 (de) * | 1973-02-23 | 1978-05-24 | C.H. Boehringer Sohn, 6507 Ingelheim | 2-Phenylamino-thienylmethyl-imidazoline-(2), Verfahren zur Herstellung derselben und diese enthaltene Arzneimittel |
| DE2830279A1 (de) * | 1978-07-10 | 1980-01-31 | Boehringer Sohn Ingelheim | 2-eckige klammer auf n-(2'-chlor-4'- methyl-thienyl-3')-n-(cyclopropylmethyl)- amino eckige klammer zu-imidazolin-(2), dessen saeureadditionssalze, dieses enthaltende arzneimittel und verfahren zu seiner herstellung |
| DE2831143A1 (de) * | 1978-07-15 | 1980-01-31 | Boehringer Sohn Ingelheim | Neue substituierte 2-phenylamino-imidazoline-(2), deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zur herstellung derselben |
| DE2831480A1 (de) * | 1978-07-18 | 1980-01-31 | Boehringer Sohn Ingelheim | Neue substituierte 2-phenylamino- imidazoline-(2), deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zur herstellung derselben |
-
1979
- 1979-12-21 DE DE19792951601 patent/DE2951601A1/de not_active Withdrawn
-
1980
- 1980-11-13 AT AT80107000T patent/ATE8260T1/de not_active IP Right Cessation
- 1980-11-13 DE DE8080107000T patent/DE3068456D1/de not_active Expired
- 1980-11-13 EP EP80107000A patent/EP0031429B1/de not_active Expired
- 1980-12-18 ZA ZA00807905A patent/ZA807905B/xx unknown
- 1980-12-18 JP JP17967480A patent/JPS5697284A/ja active Pending
- 1980-12-18 NO NO803862A patent/NO154091C/no unknown
- 1980-12-19 AU AU65602/80A patent/AU538931B2/en not_active Ceased
- 1980-12-19 ES ES497948A patent/ES8202554A1/es not_active Expired
- 1980-12-19 DK DK544980A patent/DK544980A/da not_active Application Discontinuation
- 1980-12-19 IE IE2690/80A patent/IE50588B1/en unknown
- 1980-12-19 CA CA000367198A patent/CA1143738A/en not_active Expired
- 1980-12-19 IL IL61769A patent/IL61769A/xx unknown
- 1980-12-19 NZ NZ195897A patent/NZ195897A/en unknown
- 1980-12-19 FI FI803969A patent/FI63940C/fi not_active IP Right Cessation
-
1982
- 1982-10-06 US US06/433,086 patent/US4478844A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE8260T1 (de) | 1984-07-15 |
| IL61769A (en) | 1984-12-31 |
| FI803969L (fi) | 1981-06-22 |
| FI63940B (fi) | 1983-05-31 |
| AU538931B2 (en) | 1984-09-06 |
| IE50588B1 (en) | 1986-05-14 |
| DK544980A (da) | 1981-06-22 |
| EP0031429A1 (de) | 1981-07-08 |
| FI63940C (fi) | 1983-09-12 |
| DE3068456D1 (en) | 1984-08-09 |
| DE2951601A1 (de) | 1981-07-02 |
| CA1143738A (en) | 1983-03-29 |
| NO154091C (no) | 1986-07-16 |
| EP0031429B1 (de) | 1984-07-04 |
| NZ195897A (en) | 1984-07-06 |
| JPS5697284A (en) | 1981-08-05 |
| US4478844A (en) | 1984-10-23 |
| ES497948A0 (es) | 1982-02-01 |
| AU6560280A (en) | 1981-06-25 |
| IL61769A0 (en) | 1981-01-30 |
| ZA807905B (en) | 1982-08-25 |
| IE802690L (en) | 1981-06-21 |
| NO803862L (no) | 1981-06-22 |
| ES8202554A1 (es) | 1982-02-01 |
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