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NO752078L - - Google Patents

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Publication number
NO752078L
NO752078L NO752078A NO752078A NO752078L NO 752078 L NO752078 L NO 752078L NO 752078 A NO752078 A NO 752078A NO 752078 A NO752078 A NO 752078A NO 752078 L NO752078 L NO 752078L
Authority
NO
Norway
Prior art keywords
formula
residue
fluorenone
stands
compound
Prior art date
Application number
NO752078A
Other languages
Norwegian (no)
Inventor
R Berthold
F Troxler
Original Assignee
Sandoz Ag
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
Priority claimed from CH838174A external-priority patent/CH602710A5/en
Priority claimed from CH838074A external-priority patent/CH599160A5/en
Application filed by Sandoz Ag filed Critical Sandoz Ag
Publication of NO752078L publication Critical patent/NO752078L/no

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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
    • C07D213/60—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 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
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
    • C07D203/10—Radicals substituted by singly bound oxygen atoms
    • 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
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • C07D295/088—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 to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Description

Fremgangsmåte for fremstilling av nye heterocykliskeProcess for the preparation of new heterocyclics

forbindelser.connections.

Foreliggende oppfinnelse vedrbrer en fremgangsmåte for fremstilling av nye heterocykliske forbindelser med formel I The present invention relates to a method for the production of new heterocyclic compounds of formula I

hvori in which

het betyr en 2-indolinqnrest som er forbundet med sidekjeden i 4-, 5-, 6-, eller 7-stilling'en av indolinsjelettet, eller betyr en ny fluorenonrest som ér forbundet med sidekjeden i 1-, 2-, 3- eller 4-stillingen av fluorenonsjelettet, og het means a 2-indoline residue that is connected to the side chain in the 4-, 5-, 6-, or 7-position of the indolin cell, or means a new fluorenone residue that is connected to the side chain in the 1-, 2-, 3- or The 4-position of the fluorenone bond, and

R står for gruppen R stands for the group

hvori n betyr tallet 2 eller 3, n' betyr tallet 1, 2, 3 eller 4 og X-X<1>betyr etylen eller vinylen, idet eventuelt i gruppen D de in which n means the number 2 or 3, n' means the number 1, 2, 3 or 4 and X-X<1>means ethylene or vinyl, where optionally in the group D the

to C-atomer i nabostilling til N-atomet hvert er substituert med en eller to alkylgrupper med 1-4 karbonatomer, two C atoms adjacent to the N atom are each substituted with one or two alkyl groups with 1-4 carbon atoms,

og syreaddisjonssalter derav.and acid addition salts thereof.

Står het for en 2-indolinon- eller en 9-fluorenonrest, betyr denne foretrukket 2-indolinon-4-yl henhv. 9-fluorenon-4-yl. If het stands for a 2-indolinone or a 9-fluorenone residue, this preferably means 2-indolinon-4-yl or 9-fluorenon-4-yl.

Står R for gruppen C, betyr X-X<1>foretrukket etylen.If R stands for the group C, X-X<1>preferably means ethylene.

Står R for gruppen D, betyr n<1>foretrukket 3 eller 4 og de C-If R stands for the group D, n<1>preferably means 3 or 4 and the C-

atomer som er i nabostilling til N-atomet er foretrukket alkylert, spesielt dialkylert. Disse alkylsubstituenter inneholder foretrukket 1 eller 2, spesielt 1 karbonatom. atoms that are adjacent to the N atom are preferably alkylated, especially dialkylated. These alkyl substituents preferably contain 1 or 2, especially 1 carbon atom.

Resten R står foretrukket for en tertiær aminogruppering, hvis nitrogenatom er sammenknyttet med forgrenede karbonatomer, som f.eks. 2, 2,5,5-tetrametylpyrolidinyl- eller 2, 2, 6, 6-t et r ame tyl - piperidinoresten. The residue R preferably stands for a tertiary amino group, whose nitrogen atom is connected to branched carbon atoms, such as e.g. 2, 2,5,5-tetramethylpyrrolidinyl- or 2,2,6,6-tetramethyl-piperidino residue.

Det særegne ved fremgangsmåten i -henhold til oppfinnelsen for fremstilling av de nye'«forbindelser med formel I og deres syreaddisjonssalter, er at en forbindelse med formel Ila The peculiarity of the method according to the invention for the production of the new compounds of formula I and their acid addition salts is that a compound of formula Ila

hvori Y står for syreresten av en reaksjonsdyktig ester, omsettes med en forbindelse med formel III in which Y stands for the acid residue of a reactive ester, is reacted with a compound of formula III

og forbindelsene med formel I utvinnes i form av baser eller som syreaddisjonssalter. and the compounds of formula I are recovered in the form of bases or as acid addition salts.

Fra de fri baser lar seg på kjent måte syreaddisjonssalter fremstille og omvendt. From the free bases, acid addition salts can be prepared in a known manner and vice versa.

Omsetningen av en forbindelse med formel Ila eller Ilb med en forbindelse med formel III kan skje analogt med for fremstilling av kjente 3-amino-2-hydroksypropoksy-forbindelser beskrevne metoder. Y står i formelen Ilb spesielt for halogen^ foretrukket klor The reaction of a compound of formula Ila or Ilb with a compound of formula III can take place analogously to methods described for the production of known 3-amino-2-hydroxypropoxy compounds. Y stands in the formula IIb in particular for halogen, preferably chlorine

eller brom, eller en gruppe I^-SC^-O-, hvori R 2 betyr fenyl, tolyll eller lavere alkyl. Omsetningen gjennomfores foretrukket i et under reaksjonsbetingelsene inert organisk losningsmiddel, f.eks. or bromo, or a group I^-SC^-O-, wherein R 2 is phenyl, tolyl or lower alkyl. The reaction is preferably carried out in an organic solvent that is inert under the reaction conditions, e.g.

i en cyklisk eller åpenkj.edet eter som dioksan eller dietylenglykol-dimetyleter. Eventuelt anvendes som losningsmiddel forbindelsen med formel III i overskudd. Omsetningen kan også gjennomfores i smelte. Reaksjonstemperaturen gir hensiktsmessig mellom romtemperatur og 200°C. Reaksjonstiden er blant annet avhengig av reaksjonstemperaturen. in a cyclic or open chain ether such as dioxane or diethylene glycol dimethyl ether. Optionally, the compound of formula III in excess is used as a solvent. The turnover can also be carried out in melt. The reaction temperature is suitably between room temperature and 200°C. The reaction time depends, among other things, on the reaction temperature.

F.ra reaksjonsblåndingen kan forbindelsene med formel I isoleres og renses etter kpnte metoder. From the reaction mixture, the compounds of formula I can be isolated and purified according to known methods.

Utgangsforbindelsene med formel Ila og Ilb er kjente eller kan fremstilles analogt med kjente metoder, ved å få ut fra tilsvarende hydroksyoksindol henhv. hydroksyfluoren-9-on. The starting compounds with formula Ila and Ilb are known or can be prepared analogously with known methods, by obtaining from the corresponding hydroxyoxindole or hydroxyfluoren-9-one.

Forbindelsene med formel III er kjente.The compounds of formula III are known.

Hvis fremstillingen av de nbdvendige utgangsforbindelser ikke er beskrevet er disse kjente eller kan fremstilles etter i og for: -'. seg kjente fremgangsmåter henhv. analogt med de her beskrevne eller analogt med i og for seg kjente fremgangsmåter. If the production of the necessary output connections is not described, these are known or can be produced according to and for: -'. known methods or analogously to those described here or analogously to methods known per se.

Forbindelsene med formel I og deres farmakologisk tålbare syreaddisjonssalter er tidligere ikke beskrevet i litteraturen. De fremviser ved dyreforsbk interessante farmakodynamiske egenskaper og kan folgelig anvendes som legemidler. The compounds of formula I and their pharmacologically tolerable acid addition salts have not previously been described in the literature. They show interesting pharmacodynamic properties in animal experiments and can therefore be used as medicines.

Spesielt fremviser de nye forbindelsene en antiarytmisk virkning, konstatert i mus med kloroform-arrytmi (metoden til Lawson, J.W., J.Pharmac exp.Ther. 160 [1.968], 22-31). De er på grunn av denne virkning egnet for behandling av forstyrrelser i hjerteslagtakten, f.eks. ved hjerteflimmer. Daglig dose ligger ved omtrent 5 til 400 mg og denne dose kan om nodvendig tilfores i 2 til 4 deldoser eller også som retardform. In particular, the new compounds exhibit an antiarrhythmic action, as observed in mice with chloroform arrhythmia (the method of Lawson, J.W., J.Pharmac exp.Ther. 160 [1.968], 22-31). Due to this effect, they are suitable for the treatment of disturbances in the heartbeat, e.g. in case of heart fibrillation. The daily dose is approximately 5 to 400 mg and this dose can, if necessary, be administered in 2 to 4 partial doses or also as a slow-release form.

Foretrukne representanter av denne forbindelsesklasse er forbindelsene med formel Ia Preferred representatives of this compound class are the compounds of formula Ia

hvori in which

het1 betyr en i 4-stilling med sidekjeden forbundet 2-indolinonrest eller en i 4-stillingen med sidekjeden forbundet 9-fluorenonrest, het1 means a 2-indolinone residue connected to the side chain in the 4-position or a 9-fluorenone residue connected to the side chain in the 4-position,

n" står for tallet 1 eller 2, ogn" stands for the number 1 or 2, and

R 1 stårofor alkyl med 1 til 4 karbonatomer,R 1 stands for alkyl with 1 to 4 carbon atoms,

og deres syreaddisjonssalter.and their acid addition salts.

Som legemiddel kan forbindelsen med formel I henhv. deres fysiologisk tålbare syreaddisjonssalter tilfores alene eller i egnet preparat-f orm. As a medicine, the compound of formula I can respectively their physiologically tolerable acid addition salts are administered alone or in a suitable preparation form.

Legemidlene kan utgjore en forbindelse med formel I i fri form eller i form av deres fysiologisk tålbare addisjonssalter med syrer, f.eks. i form av en losning eller en tablett, som kan fremstilles etter kjente metoder under anvendelse av vanlige hjelpe- og bærer-stoffer. The drugs can constitute a compound of formula I in free form or in the form of their physiologically tolerable addition salts with acids, e.g. in the form of a solution or a tablet, which can be prepared according to known methods using common excipients and carriers.

I de etterfolgende eksempler som skal illustrere oppfinnelsen, er alle temperaturangivelser i grader celsius. In the following examples to illustrate the invention, all temperature indications are in degrees Celsius.

Eksempel 1: 4-/ 2- hvdroksv- 3- ( 2, 2. 5, 5- tetrametvl=rl- pyrfolidinyl) Example 1: 4-/2-hydroxy-3-(2,2.5,5-tetramethyl=1-pyrfolidinyl)

propoksy7- 9- fluorenon.propoxy7-9-fluorenone.

4 g 4-(2,3-epoksypropoksy)-9-fluorenon oppvarmes sammen med 4 g 2, 2, 5,5-tetrametylpyrrolidin i 30 ml dioksan i 15 timer i autoklav ved 150°C. Etter avkjblingen inndampes reaksjonsblåndingen. Resten opptas i eter og ekstraheres med 2 N saltsyre." Den"vandige -lbsning innstilles alkalisk og ekstraheres fullstendig med metylenklorid. Metylenklbridfasen inndampes og resten krystalliseres fra eddiksyreetylester/petroleter. Smeltepunkt av den i overskriften nevnte forbindelse: 137-139°C. 4 g of 4-(2,3-epoxypropoxy)-9-fluorenone is heated together with 4 g of 2,2,5,5-tetramethylpyrrolidine in 30 ml of dioxane for 15 hours in an autoclave at 150°C. After quenching, the reaction mixture is evaporated. The residue is taken up in ether and extracted with 2 N hydrochloric acid. The aqueous solution is made alkaline and extracted completely with methylene chloride. The methylene chloride phase is evaporated and the residue is crystallized from acetic acid ethyl ester/petroleum ether. Melting point of the compound mentioned in the title: 137-139°C.

Eksempel 2: 4-/3-( 1- aziridinyl)- 2- hydroksypropoksy7- 9- fluorenon.Example 2: 4-[3-(1-aziridinyl)-2-hydroxypropoxy7-9-fluorenone.

4 g 4-(2,3-epoksypropoksy)-9-fluorenon settes bort over natten ved romtemperatur sammen med 15 ml etylenimin. Overskudd.av etylenirhin avdampesj. resten opptas i eter og lbsningen inndampes til begynnende krystallisering.• 4 g of 4-(2,3-epoxypropoxy)-9-fluorenone are set aside overnight at room temperature together with 15 ml of ethyleneimine. Surplus of ethylene irhine evaporates. the residue is taken up in ether and the solvent is evaporated to initial crystallization.•

Smeltepunkt av den i overskriften nevnte forbindelse: 113 - 116°C. Melting point of the compound mentioned in the title: 113 - 116°C.

Eksempel 3: 4-/ 2- hydroksy- 3-( 1, 2- dihydro- 2- imino- l- pyrimidinyl) Example 3: 4-/2-hydroxy-3-(1,2-dihydro-2-imino-1-pyrimidinyl)

propoksY7~ 9- fluororenon.propoxY7~ 9- fluororenone.

5 g 4-( 2,3-epoksypropoksy)-9-fluorenon og 3,8 g 2-amino-pyrimidin oppvarmes i ,30 minutter ved 100°C. Smeiten opptas i etylacetat og ekstraheres med 2-rn saltsyre. Det som harpiks utfeldte hydroklorid innstilles alkalisk og ekstraheres med metylenklorid. Losningsmiddelet avdampes og resten krystalliseres fra etanol. 5 g of 4-(2,3-epoxypropoxy)-9-fluorenone and 3.8 g of 2-amino-pyrimidine are heated for 30 minutes at 100°C. The mixture is taken up in ethyl acetate and extracted with 2N hydrochloric acid. The hydrochloride precipitated as a resin is made alkaline and extracted with methylene chloride. The solvent is evaporated and the residue is crystallized from ethanol.

(smeltepunkt 178 - 179°C).(melting point 178 - 179°C).

På analog måte erholdes ved å gå ut fra de tilsvarende utgangsforbindelser med formler Ila henhv. Ilb, hvori Y betyr klor, og III, fblgende forbindelser med formel I In an analogous way, starting from the corresponding output connections with formulas Ila or Ilb, in which Y means chlorine, and III, the following compounds of formula I

Claims (4)

1. Fremgangsmåte for fremstilling av nye heterocykliske forbindelser med formel I 1. Process for the preparation of new heterocyclic compounds of formula I hvori het betyr en 2-indolinonrest som i 4-, 5-, 6- eller 7-stillingen av indolinonsjelettet er forbundet med en sidekjede eller betyr en 9-fluorenonrest som i 1-, 2-, 3- eller 4-stillingen av fluorenonsjelettet er forbundet med sidekjeden, og R står for gruppen A in which het means a 2-indolinone residue which in the 4-, 5-, 6- or 7-position of the indolinone chain is connected with a side chain or means a 9-fluorenone residue which in the 1-, 2-, 3- or 4-position of the fluorenone chain is connected to the side chain, and R stands for group A hvori n betyr tallet 2 eller 3, n' betyr tallet 1, 2,,3 eller 4 og X-X <1> betyr etylen eller vinylen, idet eventuelt i gruppen D de to C-atomer i nabostilling til N-atomet hvert er substituert med en eller to alkylgrupper med 1-4 karbonatomer, og deres syreaddisjonssalter derav, karakterisert ved at en forbindelse med formel Ila hvori Y står for syreresten av en reaksjonsdyktig ester, omsettes med en forbindelse med formel III in which n means the number 2 or 3, n' means the number 1, 2, 3 or 4 and X-X <1> means ethylene or vinylene, possibly in the group D the two C atoms adjacent to the N atom each being substituted with one or two alkyl groups with 1-4 carbon atoms, and their acid addition salts thereof, characterized in that a compound of formula Ila in which Y stands for the acid residue of a reactive ester is reacted with a compound of formula III hvori R har den ovennevnte betydning, og forbindelsene med formel I utvinnes i form av baser eller som syreaddisjonssalter.wherein R has the above meaning, and the compounds of formula I are recovered in the form of bases or as acid addition salts. 2. Fremgangsmåte som angitt i krav 1, karakterisert ved at 4-/2-hydroksy-3- (2, 2, 5,-5-tetrametyl-l-pyrrolidinyl)propoksyJ7-9.ifluorenon fremstilles.2. Method as set forth in claim 1, characterized in that 4-(2-hydroxy-3-(2,2,5,-5-tetramethyl-1-pyrrolidinyl)propoxyJ7-9.ifluorenone is prepared. 3. Fremgangsmåte som angitt i krav 1, karakterisert ved at 4-/2-hydroksy-3-(2,2,6,6-tetrametyl-piperidino)propoksY7~ 2-indolinon fremstilles.3. Process as set forth in claim 1, characterized in that 4-(2-hydroxy-3-(2,2,6,6-tetramethyl-piperidino)propoxY7~ 2-indolinone is prepared. 4. Fremgangsmåte som angitt i krav 1, karakterisert ved at 4-/2-hydroksy-3- (2, 2, 6, 6-' tetrametyl-piperidino)propoksY7 -9-fluorenon fremstilles.4. Process as set forth in claim 1, characterized in that 4-(2-hydroxy-3-(2,2,6,6-'tetramethyl-piperidino)propoxY7-9-fluorenone is prepared.
NO752078A 1974-06-19 1975-06-11 NO752078L (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH838174A CH602710A5 (en) 1974-06-19 1974-06-19 Substd. 9-fluorenone and 2-indolinone derivs
CH838074A CH599160A5 (en) 1974-06-19 1974-06-19 Substd. 9-fluorenone and 2-indolinone derivs

Publications (1)

Publication Number Publication Date
NO752078L true NO752078L (en) 1975-12-22

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NO752078A NO752078L (en) 1974-06-19 1975-06-11

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JP (1) JPS51125060A (en)
AT (1) ATA466375A (en)
AU (1) AU8216875A (en)
CA (1) CA1036163A (en)
DD (1) DD118086A5 (en)
DE (1) DE2525656A1 (en)
DK (1) DK259475A (en)
ES (1) ES438637A1 (en)
FI (1) FI751727A (en)
FR (1) FR2275200A1 (en)
GB (1) GB1500063A (en)
HU (1) HU169926B (en)
IE (1) IE41562B1 (en)
IL (1) IL47503A0 (en)
NL (1) NL7507131A (en)
NO (1) NO752078L (en)
SE (1) SE7506757L (en)
SU (1) SU583755A3 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0005828B1 (en) * 1978-06-06 1981-03-11 Hoechst Aktiengesellschaft New substituted phenylpiperazine derivatives, pharmaceutical compositions containing them and process for their preparation
EP1144384B1 (en) 1999-01-22 2007-10-31 Elan Pharmaceuticals, Inc. Compounds which inhibit leukocyte adhesion mediated by vla-4
TW200307671A (en) 2002-05-24 2003-12-16 Elan Pharm Inc Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins
TWI281470B (en) 2002-05-24 2007-05-21 Elan Pharm Inc Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins
US7727996B2 (en) 2005-09-29 2010-06-01 Elan Pharmaceuticals, Inc. Carbamate compounds which inhibit leukocyte adhesion mediated by VLA-4
AU2006297220B8 (en) 2005-09-29 2013-01-31 Elan Pharmaceuticals, Inc. Pyrimidinyl amide compounds which inhibit leukocyte adhesion mediated by VLA-4
MX2008010988A (en) 2006-02-27 2008-10-20 Elan Pharm Inc Pyrimidinyl sulfonamide compounds which inhibit leukocyte adhesion mediated by vla-4.
US8367836B2 (en) 2009-04-27 2013-02-05 Elan Pharmaceuticals, Inc. Pyridinone antagonists of alpha-4 integrins

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SU583755A3 (en) 1977-12-05
GB1500063A (en) 1978-02-08
AU8216875A (en) 1976-12-23
DD118086A5 (en) 1976-02-12
IL47503A0 (en) 1975-08-31
NL7507131A (en) 1975-12-23
SE7506757L (en) 1975-12-22
CA1036163A (en) 1978-08-08
FI751727A (en) 1975-12-20
IE41562L (en) 1975-12-19
JPS51125060A (en) 1976-11-01
ES438637A1 (en) 1977-06-01
DE2525656A1 (en) 1976-01-15
DK259475A (en) 1975-12-20
FR2275200A1 (en) 1976-01-16
IE41562B1 (en) 1980-01-30
FR2275200B1 (en) 1979-06-08
HU169926B (en) 1977-02-28
ATA466375A (en) 1979-08-15

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