NO821725L - Fremgangsmaate for fremstilling av heterocykliske amidoxim-derivater. - Google Patents
Fremgangsmaate for fremstilling av heterocykliske amidoxim-derivater.Info
- Publication number
- NO821725L NO821725L NO821725A NO821725A NO821725L NO 821725 L NO821725 L NO 821725L NO 821725 A NO821725 A NO 821725A NO 821725 A NO821725 A NO 821725A NO 821725 L NO821725 L NO 821725L
- Authority
- NO
- Norway
- Prior art keywords
- oxo
- dihydro
- methyl
- derivatives
- heterocyclic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- -1 1-oxo-1H-isoquinolin-2-yl 2- oxo-2H- quinolin-1-yl Chemical group 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 7
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
- 206010015995 Eyelid ptosis Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 2
- 229960003147 reserpine Drugs 0.000 description 2
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- JNAYPRPPXRWGQO-UHFFFAOYSA-N 2-chloropropanenitrile Chemical compound CC(Cl)C#N JNAYPRPPXRWGQO-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
Landscapes
- 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)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (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)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av terapeutisk aktive heterosykliske amidoksim-derivater med den generelle formel (I)
hvori
R'1 representerer hydrogen eller metyl og
R representerer et radikal valgt fra gruppen bestående av 1- okso—lH-isoquinolim-2-ylr,
2- okso-2H-quinolin-»l-yl,
2,3-dihydro-lH-indol-l-yl,
1,3-diokso-l,3-dihydro-2H-isoindol- 2-yl, lH-indol-1-yl,
1-okso-l,3-dihydro-2H-isoindol— 2-yl,
2-okso-3, 4-dihydro—2H- quinolin-l-yl,
5-klor-3-metyl—2-okso-2,3—dihydro—lH-benzimida-zol-l-yl, 5-klor-2-okso-3-fenyl-2,3-dihydro—lH-benzimida-zol—1-yl,
4-klor-1-okso-lH-isoquinolin—2-yl og 3-metyl— 2-okso—2,S-dihydro—SLH-benzimidazol^l-yl,
såvel som deres addisjonssalter med farmasøytisk tålbare syrer, og racemater og enantiomerer av derivatene hvori R' er CH^, og det særegne ved fremgangsmåten i henhold til oppfinnelsen er at en forbindelse RH
hvori R har den ovennevnte betydning, reageres med et nitril
hvori R nar den ovennevnte betydning, i nærvær av natrium--hy-d-rid-hvoretter det oppnådde nitril med formel
hvori R og R' har den ovennevnte betydning, reagerer' med • hydroksylamin-hydroklorid.
1
! ■ , • . ■ ■
Disse trekk ved oppfinnelsen fremgår av patentkravet.
Amidoksimer er tidligere beskrevet i litteraturen, f.eks. i de franske patentskrifter 74 01 286 og.78 11 024.
Reaksjonen mellom nitrilet og forbindelsen RH i nærvær av natriumhydrid gjennomføres i et løsningsmiddel som f.eks. dimetylformamid og reaksjonen mellom det oppnådde nitril og hydroksylamin-hydrokloridet gjennomføres i et løsnings-middel som f.eks. en alkohol, i nærvær av en ekvivalent mengde base for oppnåelse av forbindelsene (I).
Utgangsforbindelsene er beskrevet i litteraturen.
Oppfinnelsen skal beskrives ved hjelp av utførelseseksempler.
EKSEMPEL 2-(csC-metyl-l-okso lH-isoquinolin)-acetamidoksim 1. 2-( oC-. metyl- li- okso lH- isoguinolin) . acetorvitril I'en' 250 ml kolbe innføres 3,4 g (0,07 mol) natriumhydrid 50% som bringes i suspensjon i 50 cm 3 tørt DMF og man til-setter dråpevis under omrøring og under tørt nitrogen en oppløsning av 10 g (0,069 mol) isokarbostyril i 100 cm tørt DMF.
Etter en times omrøring ved vanlig temperatur er reaksjonen oppnådd.
Denne oppløsning tilsettes dråpevis til en oppløsning av 7,16 g (0,08 mol) 2-klor propionnitril i 100 cm 3 tørt DMF avkjølt til -10°C.
Etter en times omrøring ved -10°C får reaksjonsblandingen stå ved vanlig temperatur og settes bort over natten under "tørt nitrogen.
DMF avdampes under redusert trykk og resten opptas i vann og ekstraheres med eter. Den organiske fase, vasket med vann og deretter tørkes over MgSO^, gir en restolje som renses på silikakolonne med COC1--C..H 5/5 og med CHC1 .
j JOD3
2. 2-( CX - metyl- l- okso lH- isoquinolin)- acetamidoksim I en 500 ml kolbe innføres 9,8 g (0,049 mol) av det fore-gående nitril og 3,5 g (0,05 mol) hydroksylamin-hydroklorid med 150 cm<3>absolutt etanol.
Til denne omrørte suspensjon under tørt nitrogen tilsettes dråpevis en oppløsning av natrumetylat fremstilt ved inn-virkning av 1,15 g natrium (0,05 mol) på 50 cm absolutt etanol. Det oppvarmes deretter i fire timer ved tilbake-løpstemperaturen. Etter avdamping av etanolen behandles
3
resten med 100 cm vann.
Produktet vaskes tre ganger med vann og tørkes og omkrystal-liseres fra en blanding EtOH-MetOH 8/2.
Etter filtrering, vasking med eter og tørking ved 60°C under vakuum oppnås produktet.
Tmp = 179 - -180°C
3. h<y>drokloridet av forbindelsen
Til en suspensjon av 8 g (0,0346 mol) av basen i 100 cm<3>absolutt etanol tilsettes et lite overskudd av saltsur eter'. Til den oppnådde klare løsning tilsettes 100 cm<3>eter og produktet bringes til krystallisasjon under om-røring. Etter filtrering, vasking med eter og tørking ved 60°C under vakuum oppnås produktet.
Tmp = 182 - 185°C (spaltning)
Forbindelsene ble underkastet farmakologiske forsøk.
Akutt giftighet ble bestemt i mus etter intraperitoneal injeksjon. LD 50 er omtrent 200 - 1000 mg/kg i.p.
Antidepresiv aktivitet ble bestemt ved hjelp av testen på antagonisme overfor reserpinptosis (Gourat C. et al., J. Pharmacol. (Paris) 8.333-350 (1977)).
Hannmus (CD1 Charles River, France, 18-22 g) mottok samtidig produktene under testing eller løsningsmidlet (tilført i.p.) og reserpin (4 mg/kg, tilført s.c).
Seksti minutter senere ble graden av palpebralptosis bedømt ved hjelp av en skala (0 - 4) for hver mus.
For' hver dose ble middelverdi for bedømmelsen og prosentvis variasjon i forhold til kontrolidyrene beregnet.
For hvert produkt ble AD 50, eller den dose som nedsetter den midlere verdi av ptosis i forhold til kontrolidyrene med 50% bestemt grafisk.
AD varierer fra 0,2 til 8 mg/kg ved i.p. tilførsel.
Disse resultater viser at forbindelsene fremstilt i samsvar med oppfinnelsen kan anvendes for behandling av forskjellige lidelser, spesielt for behandling av forskjellige lidel-
ser i det sentrale nervesystem og for behandling av depre-sjoner .
Forbindelsene kan tilføres på vanlig: måte ved oral, parenteral eller endorektal tilførsel, f.eks. i 'form av tabletter, drageer, geler, injiserbare eller drikkbare oppløsninger,
etc, eventuelt sammen med vanlige tilsetningsmidler.
pagelig dose kan utgjøre 5 - 500 mg.
Claims (1)
- Fremgangsmåte for fremstilling av heterosykliske amidoksim- derivater med formel (I)hvori R' representerer hydrogen eller metyl, og R representerer et radikal valgt fra gruppen bestående av 1- okso-lH-isoquinolin-2-yl 2- okso-2H- quinolin-l-yl, 2,3-dihydro-lH-indol-l-yl 1,3-diokso-l,3-dihydro-2H-isoindol-2-yl, lH-indol-l-yl, 1- okso-l,3-dihydro-2H-isoindol-2-yl, 2- okso-3,4-dihydro-2H-quinolin-l-yl, 5-klor-3-metyl-2-okso-2,3-dihydro-lH-benzimidazol-l-yl, 5-klor-2-okso-3-fenyl-2,3-dihydro-lH-benzimidazol-l-yl, 4-klor-l-okso-lH-isoquinolin-2-yl, og 3- metyl-2-okso-2,3dihydro-lH-benzimida-zolr-l-yl, såvel som deres addisjonssalter med farmasøytisk tålbare syrer, og rasemater og enåntiomerer av forbindelser hvori R'er CH3 , karakterisert ved at.en forbindelse RH, hvori R har den ovennevnte betydning, reageres med et nitril hvori R' har den ovennevnte betydning, i nærvær av natriumhydrid hvoretter det oppnådde nitril med formelHvori R og R'har den ovennevnte betydning, reagegerer med hydroksylamin-hydroklorid.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8110428A FR2506767A1 (fr) | 1981-05-26 | 1981-05-26 | Derives heterocycliques d'amidoximes, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO821725L true NO821725L (no) | 1982-11-29 |
Family
ID=9258896
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO821725A NO821725L (no) | 1981-05-26 | 1982-05-25 | Fremgangsmaate for fremstilling av heterocykliske amidoxim-derivater. |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US4438121A (no) |
| EP (1) | EP0067094B1 (no) |
| JP (1) | JPS57206663A (no) |
| AR (1) | AR230047A1 (no) |
| AT (1) | ATE15894T1 (no) |
| AU (1) | AU550769B2 (no) |
| CA (1) | CA1185603A (no) |
| DE (1) | DE3266640D1 (no) |
| DK (1) | DK234182A (no) |
| ES (1) | ES512520A0 (no) |
| FI (1) | FI821857A0 (no) |
| FR (1) | FR2506767A1 (no) |
| GR (1) | GR76445B (no) |
| HU (1) | HU186515B (no) |
| IL (1) | IL65876A (no) |
| NO (1) | NO821725L (no) |
| NZ (1) | NZ200729A (no) |
| PT (1) | PT74952B (no) |
| ZA (1) | ZA823628B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2506767A1 (fr) * | 1981-05-26 | 1982-12-03 | Synthelabo | Derives heterocycliques d'amidoximes, leur preparation et leur application en therapeutique |
| FR2564461B1 (fr) * | 1984-05-15 | 1986-09-19 | Synthelabo | Derives d'isoquinoleine, leur preparation et leurs applications |
| TW200643015A (en) * | 2005-03-11 | 2006-12-16 | Akzo Nobel Nv | 2-(4-oxo-4H-quinazolin-3-yl)acetamide derivatives |
| KR20090107994A (ko) * | 2006-09-11 | 2009-10-14 | 엔.브이.오가논 | 퀴나졸리논 및 이소퀴놀리논 아세트아미드 유도체 |
| EP2066640B1 (en) * | 2006-09-11 | 2011-09-07 | N.V. Organon | 2-(1-oxo-1h-isoquinolin-2-yl) acetamide derivatives |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2425288A (en) * | 1945-01-08 | 1947-08-05 | Commercial Solvents Corp | Plasticized butadiene polymer compositions containing phthalimidoalkyl alkanoates |
| US3291799A (en) | 1964-09-21 | 1966-12-13 | Hoffmann La Roche | Isoquinoline carboxamidine |
| DE1670497C3 (de) | 1967-06-06 | 1973-12-20 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt, Budapest | Isochinohnderivate und Verfahren zu deren Herstellung |
| US3635974A (en) * | 1968-12-20 | 1972-01-18 | Boehringer Sohn Ingelheim | Alpha-phenyl-2-aminomethyl-benzylalcohols and salts thereof |
| US3686184A (en) | 1969-04-21 | 1972-08-22 | Sterling Drug Inc | 3,4-dihydro-2(1h)-isoquinolinecarboxamidoximes |
| US3795735A (en) * | 1969-12-08 | 1974-03-05 | American Cyanamid Co | Antimicrobial nitroimidazolyl-1,2,4-oxadiazoles |
| US3654299A (en) * | 1969-12-08 | 1972-04-04 | American Cyanamid Co | Nitroimidazolyl antimicrobial agents |
| US3658832A (en) * | 1969-12-08 | 1972-04-25 | American Cyanamid Co | Novel antimicrobial nitroimidazolyl-1 2 4-oxadiazoles |
| FR2150590A1 (en) * | 1971-08-27 | 1973-04-13 | Ferlux | N (2-phenyl-3-pyridayon-4-yl)piperalines - with analgesic antipyretic antiinflammatory and hypotensive activity |
| BE792182A (fr) * | 1971-12-03 | 1973-06-01 | Hoffmann La Roche | 5-nitro-imidazoles |
| US3927000A (en) | 1972-08-21 | 1975-12-16 | Sterling Drug Inc | 1(OR 3) Perfluoroalkyl-3,4-dihydro-2(1H)-isoquinolinecarbonitriles and intermediates |
| IL44350A0 (en) * | 1973-04-05 | 1974-06-30 | Sparamedica Ag | New imidazole derivatives,their manufacture and pharmaceutical compositions containing them |
| FR2257273B1 (no) | 1974-01-15 | 1978-01-13 | Labaz | |
| US3984470A (en) | 1974-01-15 | 1976-10-05 | Labaz | Amidoxime derivatives and process for preparing the same |
| GB1477607A (en) | 1975-03-13 | 1977-06-22 | Roche Products Ltd | 2-amidino-4-hydroxy-1,2,3,4-tetrahydroisoquinoline and salts thereof |
| CH623971B5 (de) * | 1976-06-04 | 1982-01-15 | Hoechst Ag | Verfahren zur herstellung neuer benzofuranderivate und deren verwendung als optische aufheller. |
| US4048176A (en) * | 1976-07-23 | 1977-09-13 | Morton-Norwich Products, Inc. | 2-(3-Methyl-4-phenyl-1,2,3,4-tetrahydro-2-isoquinolyl)-acetamidoxime dihydrochloride |
| GB1602110A (en) * | 1977-04-21 | 1981-11-04 | Lafon Labor | Acetamidoxime derivatives |
| US4265911A (en) | 1979-10-09 | 1981-05-05 | Synthelabo | Propionamidoxime derivatives |
| FR2506767A1 (fr) * | 1981-05-26 | 1982-12-03 | Synthelabo | Derives heterocycliques d'amidoximes, leur preparation et leur application en therapeutique |
-
1981
- 1981-05-26 FR FR8110428A patent/FR2506767A1/fr active Granted
-
1982
- 1982-05-18 AT AT82400920T patent/ATE15894T1/de active
- 1982-05-18 DE DE8282400920T patent/DE3266640D1/de not_active Expired
- 1982-05-18 EP EP82400920A patent/EP0067094B1/fr not_active Expired
- 1982-05-24 AR AR289500A patent/AR230047A1/es active
- 1982-05-25 ES ES512520A patent/ES512520A0/es active Granted
- 1982-05-25 NO NO821725A patent/NO821725L/no unknown
- 1982-05-25 AU AU84157/82A patent/AU550769B2/en not_active Ceased
- 1982-05-25 US US06/381,749 patent/US4438121A/en not_active Expired - Fee Related
- 1982-05-25 HU HU821693A patent/HU186515B/hu unknown
- 1982-05-25 PT PT74952A patent/PT74952B/pt unknown
- 1982-05-25 FI FI821857A patent/FI821857A0/fi not_active Application Discontinuation
- 1982-05-25 ZA ZA823628A patent/ZA823628B/xx unknown
- 1982-05-25 GR GR68258A patent/GR76445B/el unknown
- 1982-05-25 DK DK234182A patent/DK234182A/da not_active Application Discontinuation
- 1982-05-25 CA CA000403620A patent/CA1185603A/en not_active Expired
- 1982-05-25 JP JP57089610A patent/JPS57206663A/ja active Granted
- 1982-05-25 NZ NZ200729A patent/NZ200729A/en unknown
- 1982-05-25 IL IL65876A patent/IL65876A/xx unknown
-
1983
- 1983-10-25 US US06/545,159 patent/US4530843A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0067094B1 (fr) | 1985-10-02 |
| ES8304086A1 (es) | 1983-02-16 |
| AR230047A1 (es) | 1984-02-29 |
| EP0067094A1 (fr) | 1982-12-15 |
| DE3266640D1 (en) | 1985-11-07 |
| ATE15894T1 (de) | 1985-10-15 |
| AU8415782A (en) | 1982-12-02 |
| FI821857A0 (fi) | 1982-05-25 |
| AU550769B2 (en) | 1986-04-10 |
| PT74952B (fr) | 1985-05-16 |
| ES512520A0 (es) | 1983-02-16 |
| FR2506767B1 (no) | 1984-02-10 |
| US4438121A (en) | 1984-03-20 |
| PT74952A (fr) | 1982-06-01 |
| IL65876A0 (en) | 1982-08-31 |
| ZA823628B (en) | 1983-03-30 |
| JPS625423B2 (no) | 1987-02-04 |
| CA1185603A (en) | 1985-04-16 |
| NZ200729A (en) | 1984-07-31 |
| DK234182A (da) | 1982-11-27 |
| FR2506767A1 (fr) | 1982-12-03 |
| JPS57206663A (en) | 1982-12-18 |
| IL65876A (en) | 1985-09-29 |
| GR76445B (no) | 1984-08-10 |
| HU186515B (en) | 1985-08-28 |
| US4530843A (en) | 1985-07-23 |
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