NO120030B - - Google Patents

Download PDF

Info

Publication number
NO120030B
NO120030B NO162689A NO16268966A NO120030B NO 120030 B NO120030 B NO 120030B NO 162689 A NO162689 A NO 162689A NO 16268966 A NO16268966 A NO 16268966A NO 120030 B NO120030 B NO 120030B
Authority
NO
Norway
Prior art keywords
phenyl
compounds
acid
formula
dimethylaminopropyl
Prior art date
Application number
NO162689A
Other languages
English (en)
Inventor
J Bernstein
J Krapcho
C Turk
Original Assignee
Squibb & Sons Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Squibb & Sons Inc filed Critical Squibb & Sons Inc
Publication of NO120030B publication Critical patent/NO120030B/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/38—2,3-Dihydro derivatives, e.g. isoflavanones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03G—ELECTROGRAPHY; ELECTROPHOTOGRAPHY; MAGNETOGRAPHY
    • G03G17/00—Electrographic processes using patterns other than charge patterns, e.g. an electric conductivity pattern; Processes involving a migration, e.g. photoelectrophoresis, photoelectrosolography; Processes involving a selective transfer, e.g. electrophoto-adhesive processes; Apparatus essentially involving a single such process
    • G03G17/04—Electrographic processes using patterns other than charge patterns, e.g. an electric conductivity pattern; Processes involving a migration, e.g. photoelectrophoresis, photoelectrosolography; Processes involving a selective transfer, e.g. electrophoto-adhesive processes; Apparatus essentially involving a single such process using photoelectrophoresis
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03G—ELECTROGRAPHY; ELECTROPHOTOGRAPHY; MAGNETOGRAPHY
    • G03G5/00—Recording members for original recording by exposure, e.g. to light, to heat, to electrons; Manufacture thereof; Selection of materials therefor
    • G03G5/12—Recording members for multicolour processes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Electrochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Electrochromic Elements, Electrophoresis, Or Variable Reflection Or Absorption Elements (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Optical Filters (AREA)
  • Vertical, Hearth, Or Arc Furnaces (AREA)

Description

Fremgangsmåte for fremstilling av analgetisk aktive forbindelser.
Denne oppfinnelse angår en fremgangsmåte til fremstilling av nye kjemiske forbindelser som har verdifulle anal-getiske egenskaper, særlig smertestillende virkning.
De analgetisk aktive forbindelser som fremstilles ved fremgangsmåten ifølge oppfinnelsen, er baser av den generelle formel I hvor A er propylen, NB er en di(lavere alkyl) aminogruppe;
Y er en enkelt C-C-binding eller -CH_-; R er lavere alkyl;
R<1>er hydrogen eller lavere alkyl; og R<2>er fenyl, og deres syreaddisjonssalter..
Betegnelsen "lavere alkyl", "lavere alkoksy" og "lavere alkylen" som her anvendt, omfatter både rette og for-grenede radikaler med fra 1 til 6 karbonatomer. Syrer som er egnet for fremstilling av syreaddisjonssaltene, omfatter blant annet uorganiske syrer, så som hydrogenhalogenidsyrene (for eksempel saltsyre og hydro,genbromid) , svovelsyre, salpeter-syre, borsyre og fosforsyre, og organiske syrer så som cykloheksansulfamidsyre, eplesyre, oksalsyre, vinsyre, sitron-syre, eddiksyre og ravsyre, teofyllin og 8-klorteofyllin.
Forbindelsene som fremstilles ved fremgangsmåten i henhold til oppfinnelsen, og deres syreaddisjonssalter er analgetisk aktive forbindelser som har smertestillende virkning. Denne virkning ble funnet å være overraskende høy når forbindelsene ble administrert oralt.
I henhold til oppfinnelsen fremstilles forbindelsene med formel I ved at mellomprodukter av formel II
1 2
hvor X, Y, R, R og R er som ovenfor definert, omsettes med et reagens som har formelen Hal-Mg-A-NB, som er fremstilt fra magnesiumpuIver og Hal-A-NB, hvor Hal betyr halogen og A og B er som definert ovenfor. Produktet som dannes ved denne reaksjon, er angitt i formel I.
Forbindelser av formel II kan fremstilles ved at ketoner av formelen
1 2
hvor X, Y, R og R er som ovenfor definert, omsettes med et alkalimetallhydrid, (for eksempel natriumhydrid) eller alkalimetallamid (for eksempel kaliumamid) og derefter med R-Hal,
hvor Hal og R er som ovenfor definert (for eksempel butyljodid, cykloheksylbromid eller benzylklorid).
Forbindelsene med formel I kan omdannes til et acyloksy-derivat ved å omsette det med slike reagenser som butyl- eller fenyllitium og derefter med et anhydrid, så som eddiksyreanhydrid, propionsyreanhydrid osv. Alkoksyderivatet kan fremstilles ved å omsette hydroksyl-sluttproduktet med ekvivalente mengder av et alkalimetallamid eller -hydrid så som natriumamid, litiumhydrid, og derefter med en ekvivalent mengde eller et overskudd av alkylhalogenid så som etyljodid, heptylklorid, decylbromid osv.
Blant utgangsmaterialene for oppfinnelsen er 2-metyl-2-fenyl-l-indanon og 2,3-dimetyl-2-fenyl-l-indanon.
Forbindelsene kan erholdes som blandinger av di-astereoisomere forbindelser eller saltene derav når disse forbindelser inneholder mer enn ett asymmetrisk karbonatom. Slike blandinger eller racemater kan skilles i de enkelte racemiske forbindelser, saltene eller de kvartære ammoniumforbindelser derav på grunnlag av fysikalsk-kjemiske forskjeller, så som oppløselighet, for eksempel ved fraksjonert krystallisasjon, eventuelt av et derivat, for eksempel salt eller kvartær ammoniumforbindelse derav. Racematene av forbindelsene kan ad-skilles i de optisk aktive d- og l-former i henhold til kjente metoder for adskillelse av racemiske forbindelser., For eksempel kan man anvende d-vinsyre, dibenzoyl-d-vinsyre, 1-eplesyre, d-kamfersulfonsyre, osv.
De følgende eksempler skal tjene til å illustrere oppfinnelsen. Alle temperaturer er i °C hvis ikke annet er angitt.
Eksempel 1
1- 3- dimetylaminopropyl)- 2- metyl- 2- fenyl- l- indanol, hydroklorid
( Isomer A)
En suspensjon av 16 g magnesiumpulver i 60 ml tørt tetrahydrofuran omrøres og behandles med ca. 50 ml av en opp-løsning av 80 g 3-dimetylaminopropylklorid i 240 ml tørt tetrahydrofuran. Noen få krystaller (ca. 100 mg) jod settes til blandingen, og derefter oppvarmes forsiktig ved en temperatur på ca. 66°C. Reaksjonen blir eksoterm og reguleres ved kort av-
i
kjøling med et isbad. Blandingen tilbakeløpsbehandles ved en temperatur på ca. 66°C under tilsetningen av resten av 3-dimetylaminopropylklorid-oppløsningen, og behandlingen fortsettes derefter i ytterligere 30 minutter.
Den ytre oppvarming avbrytes under tilsetning (20 minutters periode) av en oppløsning av 50 g 2-metyl-2-fenyl-l-indanon i 250 ml tørt tetrahydrofuran, den resulterende blanding tilbakeløpsbehandles i 6 timer ved en temperatur på ca. 66°C, får stå natten over ved romtemperatur og settes derefter til en kald oppløsning av 300 g ammoniumklorid i 1,5 liter vann.Blandingen ekstraheres flere ganger med eter, de organiske faser kombineres, tørkes over magnesiumsulfat og filtreres. Filtratet konsentreres på en roterende fordamper for å gi et krystallinsk residuum. Sistnevnte behandles med 2 liter eter og 200 ml vann, og blandingen rystes. Den organiske fase tørkes over magnesiumsulfat, filtreres og konsentreres for å gi 56 g krystallinsk residuum med et smeltepunkt på ca. 93-120°C. Dette materialet oppsluttes med 350 ml varm heksan, hvilket efterlater 4,8 g uoppløselig materiale med et smeltepunkt ca. 134-136°C. Av-kjøling av heksanoppløsningen gir 39,0 g materiale med et smeltepunkt ca. 98-120°C. Dette materiale suspenderes i 200
ml eter, og man får tilbake 8,9 g uoppløselig materiale med et smeltepunkt ca. 134-136°C. Konsentrering av de kombinerte heksan- og eteroppløsninger gir 38 g av et fast materiale med smeltepunkt ca. 93-96°C. Omkrystallisering fra 150 ml heksan gir 27,3 g av et fast stoff med et smeltepunkt ca. 98-loo°C.
Sistnevnte materiale oppløses i 125 ml etanol og behandles med 17 ml 5,9 N alkoholisk hydrogenklorid, og den resulterende oppløsning fortynnes til ca. 1 liter med vannfri eter for å gi 22 g farveløst, fast stoff med smeltepunkt ca. 163-165°C. Efter krystallisering fra 90 ml etanol-900 ml eter, smelter det farveløse, faste stoff 1-(3-dimetylaminopropyl)-2-metyl-2-fenyl-l-indanol, hydroklorid ved 171-173°C.
Eksempel 2
1-( 3- dimetylaminopropyl)- 2- metyl- 2- fenyl- l- indanol, hydroklorid
( Isomer B)
De to fraksjoner av materiale fra eksempel 1 som smelter ved 134-136°C (4,8 og 8,9 g), kombineres og krystalli-seres fra 75 ml acetonitril for å gi 11,2 g produkt med et smeltepunkt ca. 134-136°C. Dette materiale oppløses i 50 ml kloroform og behandles med 7 ml 5,5 N alkoholisk hydrogenklorid. Fortynning av denne oppløsning med 400 ml eter gir 10,5 g fast stoff med et smeltepunkt ca. 157-161°C. Efter krystallisering fra 30 ml metanol-300 ml eter, smelter det farveløse, faste stoff 1-(3-dimetylaminopropyl)-2-metyl-2-fenyl-l-indanol, hydroklorid ved 173-175°C.
Eksempel 3
1~( 3- dimetylaminopropyl)- 1, 2, 3, 4- tetrahydro- 2- metyl- 2- fenyl- l-naftol, hydroklorid ( IsomerB)
Ved å følge fremgangsmåten fra eksempel 1, men ved
å anvende en ekvivalent mengde av 2-metyl-2-fenyltetralon istedenfor 2-metyl-2-fenyl-l-indanon, får man 65 g av produktet i form av en fri base som er en blanding av isomerer. Ved å opp-løse dette materiale i 130 ml heksan, krystalliserer isomer B
i ren form, vekt 33,0 g, smeltepunkt 77-79°C. En oppløsning av 28,4 g av dette materiale i 50 ml etanol og 50 ml eter behandles med 26,2 ml 3,4 N alkoholisk hydrogenklorid, og den resulterende oppløsning fortynnes til 600 ml eter for å gi 31,5 g av et farveløst, fast stoff med et smeltepunkt 214-215°C.
Konsentrering under redusert trykk av heksanfiltratet som gir 33 g av isomer B, gir isomer A. Denne base omdannes til hydrokloridsaltet på samme måte som beskrevet for isomer B. Hydrokloridsaltet av isomer A smelter ved 155-157°C.
Eksempel 4
1-( 3- dimetylaminopropyl)- 2, 3- dimetyl- 2- fenyl- l- indanol, hydroklorid
Under anvendelse av fremgangsmåten fra eksempel 1,
men ved å anvende en ekvivalent molar mengde av 2,3-dimetyl-2-feny] 1-indanon istedenfor 2-metyl-2-fenylindanon, får man 1-(3-di-metylaminopropyl) -2,3-dimetyl-2-fenyl-l-indanol, hydroklorid med et smeltepunkt på 192-194°.
Sammenlignende forsøk vedrørende smertestillende aktivitet
Voksne han-albinomus ble undersøkt. Før undersøk-elsen ble alle forsøksdyrene sultet i 16 til 18 timer og fikk drikke alt vann de ønsket. Ved alle sammenlignende forsøk ble sulfatene av kodein og hydrokloridene av meperidin anvendt.
Den smertestillende virkning for forbindelsene fremstilt i henhold til oppfinnelsen ble bestemt ved metoden ifølge D'Amour og Smith, J. Pharmacology 1941, 72, 74, og ble sammen-lignet med aktivitetene for meperidin, kodein og propoksyfen, som ble bestemt på samme måte.Forsinkningen i "hale-slag" reaksjonen på en konstant varmepåvirkning på halen utgjorde et mål for smertestillende virkning. For å unngå å skade dyrenes halser ble den maksimale varighet av varmebehandlingen satt til det dobbelte av reaksjonstiden før administrering av middelet. Orale doser varierende fra 261/2 til 105 mg pr. kg ble anvendt.
Hale-slag-metoden ga nøyaktige beregninger av middels smertestillende doser (EDC,_) for alle forbindelsene i tabell 1.
DU
1-(3-dimetylaminopropyl)-2-metyl-2-fenyl-l-indanol hydroklorid (Isomer A), forbindelsen ifølge eksempel 1, var omtrentlig fire ganger så aktiv som meperidin, kodeinsulfat eller propoksyfen. 1-(3-dimetylaminopropyl)-2-metyl-2-fenyl-l-indanol hydroklorid (Isomer B), forbindelsen ifølge eksempel 2, var omtrentlig to ganger så aktiv som meperidin, kodeinsulfat og propoksyfen. 1-(3-dimetylaminopropyl)-1,2,3,4-tetrahydro-2-metyl-2-fenyl-l-naftol, hydroklorid (Isomer A), forbindelsen ifølge eksempel 3, var mer enn tre ganger så aktiv som meperidin, kodeinsulfat og propoksyfen. 1-(3-dimetylaminopropyl)-2,3-dimetyl-2-fenyl-l-indanol, hydroklorid, forbindelsen ifølge
eksempel 4, var omtrentlig to ganger så aktiv som meperidin, kodeinsulfat og propoksyfen.

Claims (1)

  1. Fremgangsmåte for fremstilling av analgetisk aktive forbindelser av formelen
    hvor A er propylen, NB er en di(lavere alkyl) aminogruppe; Y er en enkelt C-C-binding eller -CH -; R er lavere alkyl; R1 er hydrogen eller lavere alkyl; og R 2er fenyl, og deres syre-addis jonssalter , karakterisert ved at en for- bindelse av formelen
    1 2 hvor Y, R, R og R er som ovenfor definert, omsettes med en forbindelse av formelen Hal-Mg-A-NB, hvor Hal er halogen og A og NB er som ovenfor definert, og eventuelt omsettes de er-holdte forbindelser med en-syre for dannelse av syreaddisjonssalter .
NO162689A 1965-03-19 1966-04-21 NO120030B (no)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US41110665A 1965-03-19 1965-03-19
US44110665A 1965-03-19 1965-03-19
US45265165A 1965-05-03 1965-05-03
US45496265A 1965-05-11 1965-05-11
US504122A US3419560A (en) 1965-03-19 1965-10-23 1-aminoalkyl 2-aryl indanes and tetrahydronaphthalenes
US59066666A 1966-10-31 1966-10-31
US79882868A 1968-11-01 1968-11-01

Publications (1)

Publication Number Publication Date
NO120030B true NO120030B (no) 1970-08-17

Family

ID=27569758

Family Applications (2)

Application Number Title Priority Date Filing Date
NO162166A NO123368B (no) 1965-03-19 1966-03-18
NO162689A NO120030B (no) 1965-03-19 1966-04-21

Family Applications Before (1)

Application Number Title Priority Date Filing Date
NO162166A NO123368B (no) 1965-03-19 1966-03-18

Country Status (11)

Country Link
US (5) US3553093A (no)
AT (3) AT286783B (no)
BE (1) BE680863A (no)
CH (3) CH479099A (no)
DE (1) DE1522742A1 (no)
FR (2) FR1568731A (no)
GB (4) GB1157671A (no)
IL (1) IL25304A (no)
NL (1) NL6606339A (no)
NO (2) NO123368B (no)
SE (2) SE334540B (no)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE371190B (no) * 1972-03-24 1974-11-11 Kabi Ab
US3804508A (en) * 1965-05-28 1974-04-16 V Mihajlov Photoelectrophoretic apparatus for heat fixing an image
US3504031A (en) * 1966-05-24 1970-03-31 Mead Johnson & Co 1-aminoalkyl-1-phenylindene process and intermediate therefor
US3477934A (en) * 1966-06-29 1969-11-11 Xerox Corp Imaging process
US3680955A (en) * 1968-07-16 1972-08-01 Minolta Camera Kk Apparatus for forming an electrostatic image in a camera
US3620950A (en) * 1968-10-03 1971-11-16 Xerox Corp Electrophoretic imaging employing periodic electromagnetic radiation
US3743404A (en) * 1968-10-03 1973-07-03 Xerox Corp Photoelectrophoretic imaging apparatus including means to simultaneously apply a compressive stress and shear stress to the imaging suspension
US3657091A (en) * 1968-10-03 1972-04-18 Xerox Corp Electrophoretic imaging method employing a periodic electric field
US3811764A (en) * 1968-10-03 1974-05-21 Xerox Corp Apparatus for photoelectrophoretic imaging using a periodic electric field
US3784302A (en) * 1968-10-03 1974-01-08 Xerox Corp Electrophoretic imaging apparatus including application of dynamic stress on the particle suspension
US3853556A (en) * 1969-05-02 1974-12-10 Xerox Corp Method for eliminating electrical arcing during photoelectrophoretic imaging
BE756481A (fr) * 1969-09-23 1971-03-22 Xerox Corp Procede de formation d'image photoelectrophoretique par reflexion
USRE28360E (en) * 1969-10-03 1975-03-04 Electrophoretic color display device
US3761174A (en) * 1969-10-31 1973-09-25 Xerox Corp Manifold web handling
US3690754A (en) * 1969-11-14 1972-09-12 Xerox Corp Control system for an optical imaging system
JPS527348B1 (no) * 1970-01-09 1977-03-01
US3909262A (en) * 1970-12-14 1975-09-30 Xerox Corp Imaging migration member employing a gelatin overcoating
US3719484A (en) * 1971-01-06 1973-03-06 Xerox Corp Photoelectrophoretic imaging method
US3751420A (en) * 1971-04-01 1973-08-07 Squibb & Sons Inc Monoolmonoene amines
US3859438A (en) * 1971-07-08 1975-01-07 Boehringer Sohn Ingelheim Pharmaceutical compositions containing an n-(1-bicyclic aryl-propyl-2)-n-bicyclic aryl-piperazine and method of use
US3984464A (en) * 1972-10-06 1976-10-05 A. Christiaens Societe Anonyme Derivatives of 2-amino-(1,2,3,4-tetrahydronaphthalene), the preparation and use thereof
US3859576A (en) * 1973-02-15 1975-01-07 Xerox Corp High performance blocking electrode for electrophotophoresis
US3905812A (en) * 1973-04-23 1975-09-16 Xerox Corp Imaging process
US3917880A (en) * 1973-06-27 1975-11-04 Xerox Corp Electrophoretic imaging system
US3945724A (en) * 1974-06-04 1976-03-23 Xerox Corporation Velocity compensation for bead bypass
US4078928A (en) * 1975-03-03 1978-03-14 Xerox Corporation Photoelectrophoretic imaging method
US4084896A (en) * 1975-04-24 1978-04-18 Xerox Corporation Photoelectrophoretic web imaging apparatus
CH619701A5 (no) * 1975-08-07 1980-10-15 Bayer Ag
US4013673A (en) * 1976-04-13 1977-03-22 Warner-Lambert Company 2,3-dihydro-3-(2-pyridinyl)-4h-1-benzopyran-4-one n-oxides
US4130359A (en) * 1976-07-23 1978-12-19 Eastman Kodak Company Electrophoretic migration imaging apparatus and method utilizing enlarged migration environment
DE2814983A1 (de) * 1978-04-07 1979-10-18 Bayer Ag Neue chromanon-derivate
CH641147A5 (de) * 1979-01-17 1984-02-15 Sandoz Ag 3-amino-2-hydroxypropoxyaryl-derivat, seine herstellung und dieses enthaltende heilmittel.
NL8003141A (nl) * 1980-05-30 1982-01-04 Akzo Nv Biologisch aktieve tricyclische aminen.
CH648030A5 (de) * 1980-12-15 1985-02-28 Sandoz Ag Benzopyran-allylaminderivate, verfahren zu ihrer herstellung und ihre verwendung.
US4321270A (en) * 1981-01-29 1982-03-23 E. R. Squibb & Sons, Inc. Substituted chromans
US4452801A (en) * 1981-09-24 1984-06-05 E. R. Squibb & Sons, Inc. Chromans including heterocyclic substituent
US4505932A (en) * 1983-05-13 1985-03-19 Abbott Laboratories Method of producing α2 -adrenergic receptor agonist activity
GB8704572D0 (en) * 1987-02-26 1987-04-01 Lundbeck & Co As H Organic compounds
US5086074A (en) * 1988-01-15 1992-02-04 Abbott Laboratories 1-aminomethyl-1,2,3,4-tetrahydronaphthalenes
EP0395734A4 (en) * 1988-01-15 1991-01-02 Abbott Laboratories 1-aminomethyl-1,2,3,4-tetrahydronaphthalenes
US5128362A (en) * 1988-01-15 1992-07-07 Abbott Laboratories 1-aminomethyl-1,2,3,4-tetrahydronaphthalenes
US5298512A (en) * 1989-04-07 1994-03-29 Pfizer Inc. Substituted chromans and their use in the treatment of asthma, arthritis and related diseases
US5500444A (en) * 1989-11-14 1996-03-19 Hoechst Marion Roussel, Inc. Cardioprotective tocopherol analogs
US5063397A (en) * 1990-05-25 1991-11-05 Xerox Corporation Variable-thickness imaging members
EP0550292A1 (en) * 1992-01-02 1993-07-07 Merrell Dow Pharmaceuticals Inc. Tissue protective tocopherol analogs
US5510373A (en) * 1992-04-06 1996-04-23 Merrell Pharmaceuticals Inc. Cardioprotective agents
US5721233A (en) * 1992-04-06 1998-02-24 Merrell Pharmaceuticals Inc. Derivatives of 2,3-dihydro benzofuranols
US5545660A (en) * 1992-04-07 1996-08-13 Merrell Pharmaceuticals Inc. Hydrazide derivatives of 3,4-dihydro-2H-1-benzopyrans
IL143780A (en) * 2001-06-14 2007-06-03 Cerel Ceramic Technologies Ltd Process for manufacturing electrode
US7339715B2 (en) * 2003-03-25 2008-03-04 E Ink Corporation Processes for the production of electrophoretic displays
DE102005010000A1 (de) * 2005-03-04 2006-09-07 Merck Patent Gmbh Indane

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2758939A (en) * 1953-12-30 1956-08-14 Rca Corp Electrostatic printing
US2987660A (en) * 1955-06-06 1961-06-06 Haloid Xerox Inc Xerographic charging
US2902974A (en) * 1956-06-14 1959-09-08 Ibm Latent electrostatic image developing apparatus
US2884434A (en) * 1957-03-07 1959-04-28 Dow Corning Haloorgano silcarbane siloxanes
US2940847A (en) * 1957-07-03 1960-06-14 None i red
US3068479A (en) * 1958-05-09 1962-12-11 Burroughs Corp Electrographic recording apparatus
US3251685A (en) * 1959-10-19 1966-05-17 Xerox Corp Method of controlling contrast in a xerographic reproduction process
US3142682A (en) * 1961-11-21 1964-07-28 Ciba Geigy Corp Tertiary amino derivatives of chromans and homo-chromans
US3271145A (en) * 1963-12-23 1966-09-06 Eastman Kodak Co Process for producing an electrostatic charge image
US3301866A (en) * 1965-08-12 1967-01-31 Rexall Drug Chemical Substituted indenopyridines

Also Published As

Publication number Publication date
US3419560A (en) 1968-12-31
IL25304A (en) 1969-11-30
US3553093A (en) 1971-01-05
DE1522743A1 (de) 1969-10-30
FR1568731A (no) 1969-05-30
AT286783B (de) 1970-12-28
US3551320A (en) 1970-12-29
GB1149666A (en) 1969-04-23
NL6606339A (no) 1966-11-14
CH479099A (fr) 1969-09-30
US3448025A (en) 1969-06-03
AT285326B (de) 1970-10-27
GB1149665A (en) 1969-04-23
US3474019A (en) 1969-10-21
AT279598B (de) 1970-03-10
DE1522742A1 (de) 1969-10-30
GB1157671A (en) 1969-07-09
SE334540B (no) 1971-04-26
FR5864M (no) 1968-03-11
DE1522743B2 (de) 1972-07-27
NO123368B (no) 1971-11-01
CH479100A (fr) 1969-09-30
CH466305A (fr) 1968-12-15
SE341330B (no) 1971-12-20
GB1149615A (en) 1969-04-23
BE680863A (no) 1966-11-14

Similar Documents

Publication Publication Date Title
NO120030B (no)
NO154294B (no) Doseinhalator.
LaForge THE PREPARATION AND PROPERTIES OF SOME NEW DERIVATIVES OF PYRIDINE1, 2
JPS625983A (ja) 新規第三ｎ−置換ノルトロピン化合物
CZ279028B6 (en) Substituted imidazolyl- or 1,2,4-triazolyl methyl benzonitriles
NO142173B (no) Analogifremgangsmaate til fremstilling av terapeutisk virksomme, 1,1-diaryl-1-oksadiazolalkylaminderivater
JPS6127388B2 (no)
NO146359B (no) Analogifremgangsmaate ved fremstilling av terapeutisk aktive cyproheptadinderivater
US2704757A (en) 5-hydroxy-3, 4, 5, 6-tetrahydropyriminines
JPH0655739B2 (ja) 新規８α‐アシルアミノエルゴリン類
NO140348B (no) Analogifremgangsmaate til fremstilling av nye terapeutisk aktive 3-(amino-2-hydroksypropoksy)-isoindolin-1-on-forbindelser
NO165144B (no) Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av interne salter av aminopyridiniumhydroksidog deres tilsvarende salter.
US2970147A (en) 3-hydroxy-nu-(heterocyclic-ethyl)-morphinans
NO162689B (no) Polar-mount festestativ for parabolantenner.
JP4427249B2 (ja) 新規デスロラタジン塩、その合成方法および医薬組成物
JPS6117826B2 (no)
US3408355A (en) Thiaxanthene derivatives
US2793212A (en) Substituted benzamidopiperidinopropanes
US4225602A (en) Tetrahydropyridine derivative useful for inhibiting blood platelet aggregation
TWI443100B (zh) 培美曲塞鹽的製法
US2265207A (en) D-lysergic acid - d - l-bjtdroxybutyl
US2485662A (en) Alpha-(aminoalkyl)-stilbenes
US3031455A (en) 1-phenethyl-4-piperidyl carbamates
US2808438A (en) Tris-[di(lower) alkylaminoalkyl]-amines
NO126374B (no)