NO752078L - - Google Patents
Info
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 7
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical group C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- -1 2-indolinon-4-yl Chemical group 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- XKKQKIKSYVPGJZ-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)fluoren-9-one Chemical compound O=C1C2=CC=CC=C2C2=C1C=CC=C2OCC1CO1 XKKQKIKSYVPGJZ-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- PYTNPSPLGMPZKM-UHFFFAOYSA-N 1-hydroxy-3h-indol-2-one Chemical compound C1=CC=C2N(O)C(=O)CC2=C1 PYTNPSPLGMPZKM-UHFFFAOYSA-N 0.000 description 1
- QUUNMPSDKIURJD-UHFFFAOYSA-N 1-hydroxyfluoren-9-one Chemical compound C12=CC=CC=C2C(=O)C2=C1C=CC=C2O QUUNMPSDKIURJD-UHFFFAOYSA-N 0.000 description 1
- FMRWQLAJBBKXDM-UHFFFAOYSA-N 2,2,5,5-tetramethylpyrrolidine Chemical compound CC1(C)CCC(C)(C)N1 FMRWQLAJBBKXDM-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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 heterocykliske
forbindelser.
Foreliggende oppfinnelse vedrbrer en fremgangsmåte for fremstilling av nye heterocykliske forbindelser med formel I
hvori
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
R står for gruppen
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 syreaddisjonssalter derav.
Står het for en 2-indolinon- eller en 9-fluorenonrest, betyr denne foretrukket 2-indolinon-4-yl henhv. 9-fluorenon-4-yl.
Står R for gruppen C, betyr X-X<1>foretrukket etylen.
Står R for gruppen D, betyr n<1>foretrukket 3 eller 4 og de C-
atomer som er i nabostilling til N-atomet er foretrukket alkylert, spesielt dialkylert. Disse alkylsubstituenter inneholder foretrukket 1 eller 2, spesielt 1 karbonatom.
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.
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
hvori Y står for syreresten av en reaksjonsdyktig ester, omsettes med en forbindelse med formel III
og forbindelsene med formel I utvinnes i form av baser eller som syreaddisjonssalter.
Fra de fri baser lar seg på kjent måte syreaddisjonssalter fremstille og omvendt.
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
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.
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.
F.ra reaksjonsblåndingen kan forbindelsene med formel I isoleres og renses etter kpnte metoder.
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.
Forbindelsene med formel III er kjente.
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.
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.
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.
Foretrukne representanter av denne forbindelsesklasse er forbindelsene med formel Ia
hvori
het1 betyr en i 4-stilling med sidekjeden forbundet 2-indolinonrest eller en i 4-stillingen med sidekjeden forbundet 9-fluorenonrest,
n" står for tallet 1 eller 2, og
R 1 stårofor alkyl med 1 til 4 karbonatomer,
og deres syreaddisjonssalter.
Som legemiddel kan forbindelsen med formel I henhv. deres fysiologisk tålbare syreaddisjonssalter tilfores alene eller i egnet preparat-f orm.
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.
I de etterfolgende eksempler som skal illustrere oppfinnelsen, er alle temperaturangivelser i grader celsius.
Eksempel 1: 4-/ 2- hvdroksv- 3- ( 2, 2. 5, 5- tetrametvl=rl- pyrfolidinyl)
propoksy7- 9- fluorenon.
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.
Eksempel 2: 4-/3-( 1- aziridinyl)- 2- hydroksypropoksy7- 9- fluorenon.
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.•
Smeltepunkt av den i overskriften nevnte forbindelse: 113 - 116°C.
Eksempel 3: 4-/ 2- hydroksy- 3-( 1, 2- dihydro- 2- imino- l- pyrimidinyl)
propoksY7~ 9- fluororenon.
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.
(smeltepunkt 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
Claims (4)
1. Fremgangsmåte for fremstilling av nye heterocykliske forbindelser med formel 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
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
hvori R har den ovennevnte betydning,
og forbindelsene med formel I utvinnes i form av baser eller som
syreaddisjonssalter.
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.
3. Fremgangsmåte som angitt i krav 1, karakterisert ved at 4-/2-hydroksy-3-(2,2,6,6-tetrametyl-piperidino)propoksY7~ 2-indolinon fremstilles.
4. Fremgangsmåte som angitt i krav 1, karakterisert ved at 4-/2-hydroksy-3- (2, 2, 6, 6-' tetrametyl-piperidino)propoksY7 -9-fluorenon fremstilles.
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 (no) | 1975-12-22 |
Family
ID=25703229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO752078A NO752078L (no) | 1974-06-19 | 1975-06-11 |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS51125060A (no) |
| AT (1) | ATA466375A (no) |
| AU (1) | AU8216875A (no) |
| CA (1) | CA1036163A (no) |
| DD (1) | DD118086A5 (no) |
| DE (1) | DE2525656A1 (no) |
| DK (1) | DK259475A (no) |
| ES (1) | ES438637A1 (no) |
| FI (1) | FI751727A7 (no) |
| FR (1) | FR2275200A1 (no) |
| GB (1) | GB1500063A (no) |
| HU (1) | HU169926B (no) |
| IE (1) | IE41562B1 (no) |
| IL (1) | IL47503A0 (no) |
| NL (1) | NL7507131A (no) |
| NO (1) | NO752078L (no) |
| SE (1) | SE7506757L (no) |
| SU (1) | SU583755A3 (no) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2960178D1 (en) * | 1978-06-06 | 1981-04-09 | Hoechst Ag | New substituted phenylpiperazine derivatives, pharmaceutical compositions containing them and process for their preparation |
| PL350050A1 (en) | 1999-01-22 | 2002-10-21 | Elan Pharm Inc | Acyl derivatives which treat vla-4 related disorders |
| TWI281470B (en) | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
| TW200307671A (en) | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
| ATE502031T1 (de) | 2005-09-29 | 2011-04-15 | Elan Pharm Inc | Carbamatverbindungen, die die durch vla-4 vermittelte leukozytenadhäsion inhibieren |
| KR20080059268A (ko) | 2005-09-29 | 2008-06-26 | 엘란 파마슈티칼스, 인크. | Ｖｌａ-4에 의해 매개되는 백혈구 부착을 억제하는피리미디닐 아미드 화합물 |
| TWI389904B (zh) | 2006-02-27 | 2013-03-21 | Elan Pharm Inc | 抑制由ｖｌａ-４所調節的白血球黏附之嘧啶磺醯胺化合物 |
| EP2424841A1 (en) | 2009-04-27 | 2012-03-07 | Elan Pharmaceuticals Inc. | Pyridinone antagonists of alpha-4 integrins |
-
1975
- 1975-06-09 DE DE19752525656 patent/DE2525656A1/de active Pending
- 1975-06-10 FI FI751727A patent/FI751727A7/fi unknown
- 1975-06-10 DK DK259475A patent/DK259475A/da unknown
- 1975-06-11 NO NO752078A patent/NO752078L/no unknown
- 1975-06-12 SE SE7506757A patent/SE7506757L/xx unknown
- 1975-06-16 NL NL7507131A patent/NL7507131A/xx not_active Application Discontinuation
- 1975-06-16 GB GB25530/75A patent/GB1500063A/en not_active Expired
- 1975-06-17 FR FR7518882A patent/FR2275200A1/fr active Granted
- 1975-06-17 HU HUSA2805A patent/HU169926B/hu unknown
- 1975-06-17 AU AU82168/75A patent/AU8216875A/en not_active Expired
- 1975-06-17 IL IL47503A patent/IL47503A0/xx unknown
- 1975-06-17 DD DD186699A patent/DD118086A5/xx unknown
- 1975-06-17 ES ES438637A patent/ES438637A1/es not_active Expired
- 1975-06-17 IE IE1359/75A patent/IE41562B1/en unknown
- 1975-06-18 CA CA229,607A patent/CA1036163A/en not_active Expired
- 1975-06-18 JP JP50073280A patent/JPS51125060A/ja active Pending
- 1975-06-18 AT AT466375A patent/ATA466375A/de not_active Application Discontinuation
- 1975-06-19 SU SU7502145931A patent/SU583755A3/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| SE7506757L (sv) | 1975-12-22 |
| ES438637A1 (es) | 1977-06-01 |
| DK259475A (da) | 1975-12-20 |
| FI751727A7 (no) | 1975-12-20 |
| IL47503A0 (en) | 1975-08-31 |
| DE2525656A1 (de) | 1976-01-15 |
| ATA466375A (de) | 1979-08-15 |
| FR2275200A1 (fr) | 1976-01-16 |
| IE41562B1 (en) | 1980-01-30 |
| SU583755A3 (ru) | 1977-12-05 |
| HU169926B (no) | 1977-02-28 |
| IE41562L (en) | 1975-12-19 |
| AU8216875A (en) | 1976-12-23 |
| GB1500063A (en) | 1978-02-08 |
| FR2275200B1 (no) | 1979-06-08 |
| DD118086A5 (no) | 1976-02-12 |
| NL7507131A (nl) | 1975-12-23 |
| JPS51125060A (en) | 1976-11-01 |
| CA1036163A (en) | 1978-08-08 |
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