NO130314B - - Google Patents
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- Publication number
- NO130314B NO130314B NO00756/70*[A NO75670A NO130314B NO 130314 B NO130314 B NO 130314B NO 75670 A NO75670 A NO 75670A NO 130314 B NO130314 B NO 130314B
- Authority
- NO
- Norway
- Prior art keywords
- azepine
- dibenz
- carboxamide
- pentetrazole
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 5
- 230000036461 convulsion Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- ZFXVFMBOFIEPII-UHFFFAOYSA-N 1h-azepine-4-carboxamide Chemical compound NC(=O)C1=CC=CNC=C1 ZFXVFMBOFIEPII-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 206010043994 Tonic convulsion Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- PIZOFBKQWNPKDK-UHFFFAOYSA-N 5-methoxybenzo[b][1]benzazepine-11-carboxamide Chemical compound COC1=CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12 PIZOFBKQWNPKDK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010053398 Clonic convulsion Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 210000004279 orbit Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- ZKHZWXLOSIGIGZ-UHFFFAOYSA-N 5-methoxy-11h-benzo[b][1]benzazepine Chemical compound COC1=CC2=CC=CC=C2NC2=CC=CC=C12 ZKHZWXLOSIGIGZ-UHFFFAOYSA-N 0.000 description 1
- ANRYPESGCUZAHS-UHFFFAOYSA-N 5-methoxybenzo[b][1]benzazepine-11-carbonyl chloride Chemical compound COC1=CC2=CC=CC=C2N(C(Cl)=O)C2=CC=CC=C12 ANRYPESGCUZAHS-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 1
- 208000012545 Psychophysiologic disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- GRTOGORTSDXSFK-XJTZBENFSA-N ajmalicine Chemical compound C1=CC=C2C(CCN3C[C@@H]4[C@H](C)OC=C([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 GRTOGORTSDXSFK-XJTZBENFSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002635 electroconvulsive therapy Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229940090016 tegretol Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
- C07D223/24—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom
- C07D223/28—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom having a single bond between positions 10 and 11
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
Arialogifremgangsmåte for fremstilling av terapeutisk aktivt 10-oxo-lO,11-dihydro-5H-dibenz^b,fJ azepin-5-karboksamid.
Nærværende oppfinnelse angår en analogifremgangsmåte for fremstilling av det hittil ukjente 10-oxo-lO,ll-dihydro-5H-dibenz[b,f]azepin-5-karboksamid med formelen I,
Dette nye JD-oxo-3D/ll-dlhydro-5H-dibenz[b,f ]azepin-5-karboksamid harverdi-; fulle farmakologiske egenskaper og en særlig hoy terapeutisk indeks. Den virker ved peroral eller rektal administrasjon sentral-dempende som f.eks. kan påvises ved iakttagelsesprover;
videre virker den antikonvulsiv, sentralmuskelavslappende og hemmer kampreaksjonen hos mus. Disse virkningskvaliteter som er blitt fastslått ved utvalgte standardforsok (sml. R. Domenjoz og W. Theobald, Arch.Int.Pharmacodyn. 120, 450 (1959) og W. Theobald et al., Arzneimittel-Forsch. 17, 561 (1967)), karakteriserer forbindelsen som egnet for behandling av psyko-somatiske forstyrrelser, epilepsi, trigeminusneuralgi og cerebral spastik.
I sammenligning med det fra dansk patent nr. 93 517 kjente 5H-dibenz[b,f]azepin-5-karboksamid virker forbindelsen med formal I kraftigere undertrykkende på elektrosjokkvirkning og langt kraftigere med hensyn til hemming av pentetrazolkrampe, hvortil kommer at dens toksisitet er lavere.
I dat etterfSigande gjengis noen sammenligningsforsok hvor folgende forbindelser blir undersokt med hensyn til deres farmakologiske virkning på forsoksdyr ved en avprovning av forholdene ved elektrosjokk og pentetrazolkrampe samt med hensyn til den akutte toksisitet:
I. 10-oxo-lO,ll-dihydror5H-dibenz[b,f]azepin-5-karboksamid
II. 5H-dibenz{b,f]azepin-5-karboksamid (kjent fra dansk
patent nr. 93.517 og under handelsnavnet 'TEGRETOL" ).
Den folgende forsoksmetodikk ble anvendt:
E lektrosjokk- rotter/ partiell hemning.
Hvite hanrotter med en vekt på 120-150 g utsettes for sjokk
ved anbringelse av elektroder i oyenhulen.' Hertil holdes rottene i nakken med den ene hånd mens elektrodene med den andre hånd' holdes-fast i oyénhuléne under ét visst trykk i en vinkel på ca. 45° til frontålplånet (vekselstrom 100 volt,
50 Hz, varighet 0,63 sek.).
Forekomsten av én tonisk strekkrampe i de bakre ekstremiteter kan kun betegnes som positiv når denne krampe varer lenger enn 1 sekund.
Stoffet som skal proves administreres peroralt 60 minutter for sjokkbehandlingen i doser pa 10, 50 og 200 "mg/kg. For hver dose av fprsoksstoffet anvendes.10 dyr.
Man bestemmer hvilken dose"av forsokspreparatet som'hemmer 50% av dyrene i den ved elektrisk pirring av hjernen utloste toniske strekkrampe i de bakre ekstremiteter. Denne art sjpkkbehandling svarer til det såkalte ''maksimale elektro-
sjokk" beskrevet i litteraturen (Swinyard E. et al., J.Pharmacpl.exp.Therap, 106, 319, 1952).
Pentetrazolkrampe mus.
Hvite hanmus med en vekt på 17-25 g får administrer-t i.p.
80 mg/kg av en 0,8%'s qpplosning a<y> pentetrazol (fortynning med en 0,9^'s NaCl-ppplosning av"Cardia.zol "■ .) .. Ved alminnelig iakttagelse bedommes forekomsten a<y> såvel kloniske som toniske kramper samt den Straub'ske.halestilling. Iakttagelsestiden strakte, seg ..;pyer.. 2..timer etter admnlstrasj on. a<y> pentetrazol.
En frisk pentetrazolppplosning fremstilles for hver forsoksdag.
Forsoksstoffet administreres peroralt 60 minutter for behandling med pentetrazol i doser på 10, 50 og 200 mg/kg.
For hver dose av forsoksstoffet anvendes 10 dyr.
Man bestemmer ved hvilken dose sv f orsoksprepa-ratet 50% av dyrene hemmes i de kloniske kramper som ut16ses ved intra-peritoneal administrasjon av 80 mg/kg pentetrazol.
Akutt toksisite- tr ( DLrQ) .
Forsoksstoffet administreres mus av begge kjonn én gang peroralt ved hjelp a<y> en Schlund-sonde, hvoretter forsoksdyrene iakttas i 8 dager.
Til bestemmelse av DL^Q interpoleres verdiene på sannsynlig-hetsnett (Schleichar und Schull, Nr. 298 1/2).
Resultater
Konklusjon:
Forbindelse I fremstilt ved den foreliggende fremgangsmåte er med hensyn til hemming av virkningen av elektrosjokk ca. 3 ganger bedre sammenlignet med det kjente stoff II, og med hensyn til hemming av pentetrazolkrampe er den- et ubestemt antall ganger bedre, dog minst 30 ganger.
Ytterligere er forbindelsen I mindre giftig. Hvis man tar toksisitetsverdien som sammenligningsgrunnlag, viser forbindelse I seg overfor forbindelse II i et enda gunstigere lys.
Forbindelsen med formel I fremstilles ifolge oppfinnelsen ved at man hydrolyserer 10-matoksy-5H-dibenz[b,f]azepin-5-karboks-amid med formelen II,
Hydrolysen foretas fortrinnsvis i en fortynnet mineralsyre, f.eks. i fortynnet saltsyre eller svovelsyre. Den kan også gjennomfores i en blanding av vann og et med vann blandbart . opplosningsmiddsl, f.eks. metanol, etanol eller dioksan i nærvær av en sur ioneutveksler. siike ioneutvekslere er f.eks. "Amberlit"Vfi- i R-100 (varemerke tilhorende firma Rohm und Haas) eller "Sowex"® (varemerke tilhorende firma Dow Chemical).
Det nye virksomme stoff administreres som foran nevnt peroralt eller rektalt. Doseringen avhenger av applikasjonsmåten, arten, alderen og den individuelle tilstand. De daglige doser av virksomt stoff ligger mellom 2,8 mg/kg og 8,5 mg/kg for varmblodige dyr. Egnede doseenhetsformer som dragéer,
tabletter eller suppositorier inneholder fortrinnsvis 30-200
mg av virksomt stoff.
Det folgende eksempel belyser nærmere fremgangsmåten for fremstilling av den nye forbindelse med formelen I. Tempera-turene er angitt i Celsiusgrader.
EKSEMPEL
a) 65 g lO-metoksy-5H-dibenz[b, f.]azepin-5Tkarbqksamid kokes med 650 ml 2-n saltsyre i 2 timer under tilbakelop. Etter
avkjoling suges reaksjpnsproduktet a<y>. Etter omkrystallisasjpn fra etanpl får man 10-oxo-lO,ll-dihydro-5H-dibenz[b,f]azepin-5-karboksamid med smeltepunkt 215-216°; utbytte 49 g, 80% av teorien.
Utgangsforbindelsen l0-metoksy-5H-dibenz[b,f]azepin-5-karboks-amid fremstilles som folger: b) 223 g 10-metoksy-5H-dibenz[b,fjazepin (se J.R. Geigy A.G., belgisk patent nr. 597 793) oppvarmes i 1500 ml absolutt
toluen under pmroring ved 30°. I reaksjonsblandingen innledes derpå en livlig strom av fosgen. Man oker den innvendige temperatur i Iqpet av 3 timer til 95° og holder deretter reaksjonsblandingen en time. ved denne temperatur. Deretter avbrytes fpsgentilfprselen, varmekilder fjernes og overskuddet a<y> fosgen blåses ut med tort nitrogen. Deretter suger man det utfallende reaksjonsprpdukt.av. Filtratet dampes inn under vannstrålevakuum pg resten krystalliseres fra etanoi.
Man får en ytterligere mengds av reaksjonsprodukt som omkrystal-liseres sammen med den forste fraksjon fra etanoi, hvoretter-10-metoksy-5H-dibenz[b,f]azepin-5-karbonylklprid smelter ved 138°; utbytte 221 g, 77% av teorien.
c) 215 g av det etter b) fremstilte karbonylklorid oppvarmes,
i 2O0O ml etanoi under tilbakelop. Man leder i lopat ay
4 timer under pniroring torr ammoniakk inn i den. kokende opplos-ning. Deretter kjoler man reaksjonsblandingen til romtemperatur pg heller den i 5000 ml vann. De utfallende krystaller suges a<y> og vaskes med vann. Det fuktige rå produkt omkrystalli-ssres fra etanpl, hvoretter man får 10-metoksy-5H-dib3nz[b,f] azepin-5-karboksamid med smeltepunkt 181°; utbytte 148 g,
73% av teorien.
Claims (1)
- Analogifremgangsmåte for fremstilling av terapeutisk aktivt 10-oxo-lO,ll-dihydro-5H-dibenz[b,f]azepin-5-karboksamid med formal I,karakterisert ved at man hydrolyserer 10-mstoksy-5H-dibanz[b,f]azepin-5-karboksamid med formel II, ''■''/i
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH358369A CH500196A (de) | 1969-03-10 | 1969-03-10 | Verfahren zur Herstellung von neuen Azepinderivaten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO130314B true NO130314B (no) | 1974-08-12 |
Family
ID=4259115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO00756/70*[A NO130314B (no) | 1969-03-10 | 1970-03-03 |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US3642775A (no) |
| AT (1) | AT298492B (no) |
| BE (1) | BE747085A (no) |
| BG (1) | BG17576A3 (no) |
| BR (1) | BR7017332D0 (no) |
| CA (1) | CA920586A (no) |
| CH (1) | CH500196A (no) |
| CS (1) | CS154294B2 (no) |
| DE (1) | DE2011087C3 (no) |
| DK (1) | DK125649B (no) |
| ES (1) | ES377279A1 (no) |
| FI (1) | FI50523C (no) |
| FR (1) | FR2034781B1 (no) |
| GB (1) | GB1310571A (no) |
| HK (1) | HK51976A (no) |
| IE (1) | IE34046B1 (no) |
| IL (1) | IL34026A (no) |
| KE (1) | KE2635A (no) |
| MY (1) | MY7600194A (no) |
| NL (1) | NL162904C (no) |
| NO (1) | NO130314B (no) |
| PL (1) | PL80549B1 (no) |
| SE (1) | SE349301B (no) |
| YU (1) | YU33862B (no) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI75561C (fi) * | 1979-10-30 | 1988-07-11 | Ciba Geigy Ag | Foerfarande foer framstaellning av 5- karbamoyl-10-oxo-10,11-dihydro-5h-dibens/b,f/azepin och daertill noedvaendiga mellanprodukter. |
| EP0108715A1 (de) * | 1982-10-15 | 1984-05-16 | Ciba-Geigy Ag | Dibenzazepincarboxamide |
| FR2700117B1 (fr) * | 1993-01-07 | 1995-02-03 | Rhone Poulenc Rorer Sa | Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens. |
| US5472714A (en) * | 1993-09-08 | 1995-12-05 | Ciba-Geigy Corporation | Double-layered oxcarbazepine tablets |
| IT1272897B (it) * | 1995-01-13 | 1997-07-01 | I F C Iniziative Finanziaarie | Processo per la produzione di 10-oxo-10,11-diidro-sh- -dibenz(b,f) azepin-5-carbossiammide |
| PT101732B (pt) * | 1995-06-30 | 1997-12-31 | Portela & Ca Sa | Novas di-hidrodibenzo<b,f>azepinas substituidas processo para a sua preparacao composicoes farmaceuticas que as contem e utilizacao dos novos compostos na preparacao de composicoes farmaceuticas empregues em doencas do sistema nervoso |
| PT101876B (pt) * | 1996-05-27 | 1999-09-30 | Portela & Ca Sa | Novos derivados de 10,11-di-hidro-10-oxo-5h-dibenzo(b,f)azepina-5-carboxamida |
| US20020022056A1 (en) * | 1997-02-14 | 2002-02-21 | Burkhard Schlutermann | Oxacarbazepine film-coated tablets |
| AT406957B (de) * | 1998-11-25 | 2000-11-27 | Dsm Fine Chem Austria Gmbh | Verfahren zur oxidation von methyl-, methylen- oder methingruppen enthaltenden substraten |
| ATE224347T1 (de) | 1998-11-25 | 2002-10-15 | Dsm Fine Chem Austria Gmbh | Verfahren zur oxidation von methyl-, methylen- oder methingruppen enthaltenden substraten |
| GB9930058D0 (en) | 1999-12-20 | 2000-02-09 | Novartis Ag | Organic compounds |
| IT1317854B1 (it) * | 2000-02-25 | 2003-07-15 | Farchemia Srl | 5-ciano-10-idrossi-10,11-diidro-5h-dibenz(b,f)azepina e procedimentiper la sua preparazione e per la sua conversione in |
| HUP0303154A3 (en) * | 2001-02-12 | 2009-08-28 | Teva Pharma | New crystal forms of oxcarbazepine and processes for their preparation |
| TW200501962A (en) * | 2003-04-01 | 2005-01-16 | Novartis Ag | Use of carbamazepine derivatives for the treatment of agitation in dementia patients |
| AU2004268381B2 (en) | 2003-09-03 | 2009-06-18 | Novartis Ag | Use of oxcarbazepine for the treatment of diabetic neuropathic pain and the improvement of sleep |
| EP1678140A2 (en) * | 2003-10-20 | 2006-07-12 | Amoli Organics Ltd. | Novel process for preparation of 10-oxo-10, 11-dihydro-5h-dibenz [b,f]azepine-5-carboxamide (oxcarbazepine) via intermediate, 10-methoxy-5h-dibenz [b,f] azepine-5-carbonylchloride |
| ITMI20040452A1 (it) * | 2004-03-09 | 2004-06-09 | Clariant Lsm Italia Spa | Processo per la preparazione di oxcarbazepina |
| US7459553B2 (en) * | 2004-03-11 | 2008-12-02 | Glenmark Generics Ltd. | Process for the preparation of carboxamide compounds |
| WO2005096709A2 (en) * | 2004-03-11 | 2005-10-20 | Sun Pharmaceutical Industries Limited | A process for the preparation of 10,11-dihydro-10-oxo-5h-dibenz[b,f]azepine-5-carboxamide |
| EP1600443A1 (en) * | 2004-05-26 | 2005-11-30 | Alberto Milanese | Process for the preparation of oxcarbazepine |
| CA2471666C (en) * | 2004-06-18 | 2009-10-13 | Apotex Pharmachem Inc. | An improved process for the preparation of oxcarbazepine and related intermediates |
| US20060252745A1 (en) * | 2005-05-06 | 2006-11-09 | Almeida Jose L D | Methods of preparing pharmaceutical compositions comprising eslicarbazepine acetate and methods of use |
| ATE496623T1 (de) | 2006-04-26 | 2011-02-15 | Supernus Pharmaceuticals Inc | Oxcarbazepin-zubereitungen für kontrollierte freisetzung mit sigmoidalem freisetzungsprofil |
| GB0700773D0 (en) * | 2007-01-15 | 2007-02-21 | Portela & Ca Sa | Drug therapies |
| US20090082335A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched oxcarbazepine |
| CN101878042B (zh) | 2007-11-28 | 2013-06-19 | 尼克塔治疗公司 | 低聚物-三环共轭物 |
| US8530647B2 (en) * | 2008-05-08 | 2013-09-10 | Mylan Laboratories Limited | Process for the preparation of oxcarbazepine |
| WO2011091050A1 (en) | 2010-01-19 | 2011-07-28 | Nektar Therapeutics | Oligomer-tricyclic conjugates |
| EP2900640A1 (en) | 2012-09-26 | 2015-08-05 | Ranbaxy Laboratories Limited | Process for the preparation of oxcarbazepine and its use as intermediate in the preparation of eslicarbazepine acetate |
| CN109069480A (zh) | 2015-12-30 | 2018-12-21 | 阿达玛斯医药公司 | 用于治疗与癫痫相关的病症的方法和组合物 |
| EP3554490B1 (en) | 2016-12-16 | 2022-02-16 | Idorsia Pharmaceuticals Ltd | Pharmaceutical combination comprising a t-type calcium channel blocker |
| US10639313B2 (en) | 2017-09-01 | 2020-05-05 | Ndsu Research Foundation | Compound for inhibition of delta-5-desaturase (D5D) and treatment of cancer and inflammation |
| CA3224977A1 (en) | 2018-09-28 | 2020-04-02 | Griffith University | Agents and methods for modulating pathogen activity using ligands of complement receptor 3 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH403767A (de) * | 1961-06-09 | 1965-12-15 | Geigy Ag J R | Verfahren zur Herstellung von neuen N-heterocyclischen Verbindungen |
-
1969
- 1969-03-10 CH CH358369A patent/CH500196A/de not_active IP Right Cessation
-
1970
- 1970-03-03 NL NL7003022.A patent/NL162904C/xx not_active IP Right Cessation
- 1970-03-03 DK DK104570AA patent/DK125649B/da not_active IP Right Cessation
- 1970-03-03 NO NO00756/70*[A patent/NO130314B/no unknown
- 1970-03-03 FI FI700559A patent/FI50523C/fi active
- 1970-03-03 SE SE02770/70A patent/SE349301B/xx unknown
- 1970-03-04 US US16552A patent/US3642775A/en not_active Expired - Lifetime
- 1970-03-05 YU YU536/70A patent/YU33862B/xx unknown
- 1970-03-09 AT AT218770A patent/AT298492B/de not_active IP Right Cessation
- 1970-03-09 BE BE747085D patent/BE747085A/xx not_active IP Right Cessation
- 1970-03-09 BG BG014133A patent/BG17576A3/xx unknown
- 1970-03-09 BR BR217332/70A patent/BR7017332D0/pt unknown
- 1970-03-09 CA CA076787A patent/CA920586A/en not_active Expired
- 1970-03-09 IE IE302/70A patent/IE34046B1/xx unknown
- 1970-03-09 GB GB1111070A patent/GB1310571A/en not_active Expired
- 1970-03-09 PL PL1970139290A patent/PL80549B1/pl unknown
- 1970-03-09 IL IL34026A patent/IL34026A/en unknown
- 1970-03-09 DE DE2011087A patent/DE2011087C3/de not_active Expired
- 1970-03-09 FR FR707008344A patent/FR2034781B1/fr not_active Expired
- 1970-03-09 ES ES377279A patent/ES377279A1/es not_active Expired
- 1970-03-09 CS CS155670A patent/CS154294B2/cs unknown
-
1971
- 1971-09-20 US US00182213A patent/US3716640A/en not_active Expired - Lifetime
-
1976
- 1976-05-31 KE KE2635*UA patent/KE2635A/xx unknown
- 1976-08-19 HK HK519/76*UA patent/HK51976A/xx unknown
- 1976-12-30 MY MY194/76A patent/MY7600194A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE34046L (en) | 1970-09-10 |
| DE2011087A1 (de) | 1970-09-24 |
| DK125649B (da) | 1973-03-19 |
| SE349301B (no) | 1972-09-25 |
| KE2635A (en) | 1976-06-11 |
| FR2034781B1 (no) | 1973-04-06 |
| IE34046B1 (en) | 1975-01-08 |
| IL34026A (en) | 1972-12-29 |
| CA920586A (en) | 1973-02-06 |
| BE747085A (fr) | 1970-09-09 |
| FI50523B (no) | 1975-12-31 |
| DE2011087C3 (de) | 1979-08-30 |
| CH500196A (de) | 1970-12-15 |
| NL162904C (nl) | 1980-07-15 |
| IL34026A0 (en) | 1970-05-21 |
| YU53670A (en) | 1977-12-31 |
| ES377279A1 (es) | 1972-12-16 |
| MY7600194A (en) | 1976-12-31 |
| BR7017332D0 (pt) | 1973-01-04 |
| FI50523C (fi) | 1976-04-12 |
| BG17576A3 (bg) | 1973-11-10 |
| NL7003022A (no) | 1970-09-14 |
| DE2011087B2 (de) | 1978-12-21 |
| FR2034781A1 (no) | 1970-12-18 |
| PL80549B1 (no) | 1975-08-30 |
| CS154294B2 (no) | 1974-03-29 |
| AT298492B (de) | 1972-05-10 |
| NL162904B (nl) | 1980-02-15 |
| HK51976A (en) | 1976-08-27 |
| US3716640A (en) | 1973-02-13 |
| YU33862B (en) | 1978-06-30 |
| US3642775A (en) | 1972-02-15 |
| GB1310571A (en) | 1973-03-21 |
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