NO163619B - Analogifremgangsmaate for fremstilling av terapeutisk aktive tetrahydro- 2-heterocykloalkylpyrido(4,3)indoler. - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive tetrahydro- 2-heterocykloalkylpyrido(4,3)indoler. Download PDFInfo
- Publication number
- NO163619B NO163619B NO863671A NO863671A NO163619B NO 163619 B NO163619 B NO 163619B NO 863671 A NO863671 A NO 863671A NO 863671 A NO863671 A NO 863671A NO 163619 B NO163619 B NO 163619B
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- Norway
- Prior art keywords
- therapeutically active
- compound
- bromine
- chlorine
- heterocycloylkylpyrido
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title description 2
- 150000002475 indoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 150000003902 salicylic acid esters Chemical class 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- -1 pyrazinylquinolinyl Chemical group 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 230000000561 anti-psychotic effect Effects 0.000 abstract 1
- 239000000164 antipsychotic agent Substances 0.000 abstract 1
- 239000002249 anxiolytic agent Substances 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 125000004971 nitroalkyl group Chemical group 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 15
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229960004738 nicotinyl alcohol Drugs 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DSGKWFGEUBCEIE-UHFFFAOYSA-N (2-carbonochloridoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C(Cl)=O DSGKWFGEUBCEIE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000001741 anti-phlogistic effect Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- DVIHKVWYFXLBEM-UHFFFAOYSA-N 2-hydroxybenzoyl chloride Chemical compound OC1=CC=CC=C1C(Cl)=O DVIHKVWYFXLBEM-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 1
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 1
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Forbindelsene:. hvor. er hydrogen, halogen, hydroksy eller alkyl;. Rer substituert eller usubstituert pyridinyl, pyrazinyi kinolinyl eller kinoksalinyl og substi i.nenteno «r aikyl, alkoksy, alkoksykarbonyl, halogen, cyano eller nitro;. og n er 2, 3, 4, 5 eller 6;. eller et farmasøytisk akseptabelt salt derav, er antipsykotiskt og anxiolytiske midler.Fremgangsmåter for fremstilling av forbindelsene er beskrevet.
Description
Fremgangsmåte ved fremstilling av en ny terapeutisk aktiv salicylsyreester...' ' •■; '
Foreliggende oppfinnelse angår en fremgangsmåte ved fremstilling av en ester av salicylsyre eller, et derivat derav, og P-pyridylcarbinol eller et derivat derav. Den aktuelle forbindelse har vist seg å ha såvel analgetisk som vasodilatorisk aktiv-itet. Den nye ester har formelen: og fremstilles ved en analogifremgangsmåte som generelt kan be-skrives som at en forbindelse med den generelle formel:
hvor R, er klor, brom, hydroxyl eller OR., hvor R. er et
1 4 4 metallatom, f.eks. natrium eller kalium, og R ? er hydrogen eller acyl, fortrinnsvis benzoyl eller Cn^ 2n.+ 1G0' hvor n er 1» 2 eller 3, omsettes med en forbindelse med den generelle formel:
hvor R^ er hydroxyl, klor eller brom.
Den nye ester fremstilles fortrinnsvis ved omsetning av acetylsalicylsyreklorid og (3-pyridylcarbinol i benzen og i nærvær av et saltsyrebindende tertiært amin. Acetylgruppen i acetylsalicylsyre virker som beskyttelsesgruppe og forhindrer den polymerisasjon som ellers lett ville kunne finne sted mellom flere salicylsyrekloridmolekyler under de aktuelle betingelser. Det vil være åpenbart at hvis en injiserbar forbindelse onskes, overfores på kjent vis de dannede forbindelser til et vevsvennlig salt, f.eks., et hydroklorid.
Eksempel 1
95,5 g (0,48 mol) acetylsalicylsyreklorid, friskt fremstilt, opplbses i 50 g benzen og dryppes under omroring og avkjbling i et reaksjonsapparat med 60 g (0,55 mol) p-pyridylcarbinol, 50 g (0,50 mol) triethylamin og 200 g benzen slik at temperaturen ikke under tilsetningen av kloridet overstiger 18°C. Reaksjonstiden avhenger av kjolekapasiteten, men bor fortrinnsvis ikke ta mere enn 2 timer. Blandingen får så efterreagere ved 20 - 25°C i 12 - 16 timer under fortsatt omroring. Ved reaksjonen dannes tri-ethylaminhydroklorid, som for størstedelen utfelles ved tilsetning av 75 g diethylether. Triethylaminhydrokloridet frafiltreres, og
den gjenværende benzenetheropplbsning inneholdende reaksjons-produktet, ace tyl salicylsyre-(3-pyridylcarbinole ster, ekstraheres med 600 g IN saltsyre. Saltsyreekstraktet oppvarmes hurtig til nær kokning, hvorefter det like hurtig avkjoles til 15 - 20°C.
Den saltsure opplosning nbytraliseres med 10%-ig ammoniakk, hvorved salicylsyre^-pyridylcarbinolester utfelles som en svakt gulaktig olje. 150 g benzen tilsettes for å opplose oljen, hvorefter vannfasen fraskilles. Benzenopplosningen vaskes med 2 x 150 g vann. Efter torring med 10 g calciumklorid og av-destillering av benzenen fåes en renset salicylsyre-P-pyridylcarbinolester, som opplbses i 200 g torret methylethylketon.
Vel torret hydrogenkloridgass innledes i methylethylketonopplbsningen hvorved hydrokloridet av salicylsyre-pyridylcarbinolester utfelles i krystallinsk form, og innledningen.fortsettes inntil en liten filtrert prove ikke gir ytterligere utfelning av klorid med hydrogenkloridgass. Hydrokloridet kan lett omkrystalliseres fra methylethylketon i nærvær av aktivt kull om bnskes. Det direkte utbytte utgjor 77 g (60%) salicylsyre-p-pyridylcarbinolester og ytterligere ca. 10% kan utvinnes ved opparbeidelse av morluter.
Eksempel 2
25,5 g 3-klormethylpyridin og 48,0 g vannfritt natrium-salicylat settes til 200 ml torr aceton, og blandingen kokes under tilbakelop i 24 timer. Acetonet avdestilleres, og det organiske residuum opplbses i 100 g benzen. Benzenopplosningen vaskes med 2 x 100 g vann, tbrres med calciumklorid, og benzenen avdestilleres. Den gjenværende olje opplbses i torr methylethylketon hvorefter vel torret hydrogenkloridgass innledes i methylethylketonopplbsningen. Hydrokloridet av salicylsyre-P-pyridylcarbinolester faller ut i krystallinsk form og frafiltreres. Utbytte 28 g (53%).
Foreliggende forbindelse har foruten vasodilatorisk virkning også analgetisk og antiflogistisk virkning. Med hen-syn til .de tre virkninger hos foreliggende forbindelse , fremgår disse av nedenstående forsok.
Vasodilatorisk effekt:
Metode: flush-test på marsvin, se Haining (1963)
Resultat:,' 10 mg/kg p.o. fremkalte flush hos 9/12 marsvin med
en flushintensitet av 6,3 middelpoeng (max. = 18 poeng), ingen av kontrolldyrene viste noen flush (for nicotinsyre er tilsvarende data: 12/12 resp.
10,7 middelpoeng).
Analgetisk effekt:
Metode: fenylkinontest på mus, se Turner (1965)
Resultat: 100 mg/kg p.o. minsket antallet "writhings" fra
170 (kontrolldyr) til 140 avlest 20 min efter applikasjon (tilsvarende tall for acetylsalicyl-
syre var 115)•
Antiflogistisk effekt:
Metode: gjærodemtest på rotter, se Selitto + Randall (1954)
Resultat: 200 mg/kg p.o.: 2 timer efter applikasjon var potevolumet 185% og 4 timer efter applikasjonen også 185% av det opprinnelige volum - kontroll-dyrenes potevolum var for samme tider 200%. resp.
230% (tilsvarende verdier efter acetylsalicylsyre var. 190% resp. 170%)..
Claims (3)
1. Fremgangsmåte ved fremstilling av en ny, terapeutisk aktiv salicylsyreester av formelen:
og farmakologisk godtagbare salter derav, karakterisert ved at en forbindelse av den generelle formel:
hvor R-^ er klor, brom, hydroxyl eller OR^, hvor R^ er et metallatom, f.eks. natrium eller kalium, og R^ er hydrogen eller acyl, fortrinnsvis benzoyl eller ^^2^1^' hvor n er 1, 2 eller 3, omsettes med en forbindelse med den generelle formel:
hvor R^ er hydroxyl, klor eller brom, og at den erholdte forbindelse, om dnskes, overfores til et salt derav på i og for seg kjent vis.
2. Fremgangsmåte ifblge krav 1, karakterisert ved at et tertiært amin anvendes for å absorbere hydrogen-klorid eller hydrogenbromid når R^ eller R^ er klor eller brom.
3. Fremgangsmåte ifblge krav 1 eller 2, karakterisert ved at et fortrinnsvis inert opplbsningsmiddel anvendes.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/776,180 US4636563A (en) | 1985-09-16 | 1985-09-16 | Antipsychotic γ-carbolines |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO863671D0 NO863671D0 (no) | 1986-09-15 |
| NO863671L NO863671L (no) | 1987-03-17 |
| NO163619B true NO163619B (no) | 1990-03-19 |
| NO163619C NO163619C (no) | 1990-06-27 |
Family
ID=25106686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO863671A NO163619C (no) | 1985-09-16 | 1986-09-15 | Analogifremgangsmaate for fremstilling av terapeutisk aktive tetrahydro- 2-heterocykloalkylpyrido(4,3)indoler. |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US4636563A (no) |
| EP (1) | EP0223344B1 (no) |
| JP (1) | JPS6267083A (no) |
| KR (1) | KR900002245B1 (no) |
| CN (1) | CN1013864B (no) |
| AR (1) | AR242208A1 (no) |
| AT (1) | ATE55770T1 (no) |
| AU (1) | AU590605B2 (no) |
| CA (1) | CA1275099A (no) |
| CY (1) | CY1595A (no) |
| DE (1) | DE3673607D1 (no) |
| DK (1) | DK440686A (no) |
| EG (1) | EG18015A (no) |
| ES (1) | ES2002656A6 (no) |
| FI (1) | FI83318C (no) |
| GB (1) | GB2180536B (no) |
| GR (1) | GR862343B (no) |
| HK (1) | HK53491A (no) |
| HU (1) | HU195217B (no) |
| IL (1) | IL79956A0 (no) |
| MX (1) | MX3681A (no) |
| NO (1) | NO163619C (no) |
| NZ (1) | NZ217580A (no) |
| PH (1) | PH22515A (no) |
| PT (1) | PT83344B (no) |
| SU (1) | SU1442074A3 (no) |
| YU (1) | YU45023B (no) |
| ZA (1) | ZA866258B (no) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5328905A (en) * | 1987-07-20 | 1994-07-12 | Duphar International Research B.V. | 8,9-anellated-1,2,3,4-tetrahydro-β-carboline derivatives |
| US5360800A (en) * | 1987-09-03 | 1994-11-01 | Glaxo Group Limited | Tetrahydro-1H-pyrido[4,3-b]indol-1-one derivatives |
| US4798896A (en) * | 1988-01-19 | 1989-01-17 | American Home Products Corporation | Antipsychotic gamma-carboline N-oxides |
| HU207078B (en) * | 1988-08-02 | 1993-03-01 | Glaxo Group Ltd | Process for producing lactam derivatives and pharmaceutical compositions comprising such compounds |
| US5008272A (en) * | 1988-08-15 | 1991-04-16 | Glaxo Group Limited | Lactam derivatives |
| US5021569A (en) * | 1990-06-12 | 1991-06-04 | American Home Products Corporation | 4-azatricyclo[4.3.1.1(3,8)]undecylarylpiperazines with anxiolytic activity |
| US5484788A (en) * | 1993-03-26 | 1996-01-16 | Beth Israel Hospital Association | Buspirone as a systemic immunosuppressant |
| US5631017A (en) * | 1993-03-26 | 1997-05-20 | Beth Israel Deaconess Medical Center, Inc. | Topical application of buspirone for treatment of pathological conditions associated with immune responses |
| CN1109880A (zh) * | 1994-02-03 | 1995-10-11 | 合成实验室公司 | 3-(2-氨基乙基)-4-[3-(三氟甲基)苯甲酰基]-3，4-二氢-2h-1，4-苯并噁嗪衍生物、制备及其应用 |
| FR2715659B1 (fr) * | 1994-02-03 | 1996-03-22 | Synthelabo | Dérivés de 3-(2-aminoéthyl)-4-[3-(trifluorométhyl)benzoyl]-3,4-dihydro-2H-1,4-benzoxazine, leur préparation et leur application en thérapeutique. |
| JP3274579B2 (ja) * | 1995-01-12 | 2002-04-15 | 住友製薬株式会社 | 脳血管障害に伴う精神症候治療剤 |
| US5637314A (en) * | 1995-06-07 | 1997-06-10 | Beth Israel Deaconess Medical Center, Inc. | Topical and systemic application of buspirone or derivatives thereof for treating atopic dermatitis |
| RU2106864C1 (ru) * | 1995-10-23 | 1998-03-20 | Николай Серафимович Зефиров | Средство для лечения болезни альцгеймера |
| RU2283108C2 (ru) * | 2003-12-08 | 2006-09-10 | Сергей Олегович Бачурин | ГЕРОПРОТЕКТОР НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| US20070179174A1 (en) * | 2003-12-08 | 2007-08-02 | Bachurin Sergei O | Methods and compositions for slowing aging |
| AU2006275694A1 (en) * | 2005-07-28 | 2007-02-08 | Bristol-Myers Squibb Company | Substituted tetrahydro-1H-pyrido(4,3,b)indoles as serotonin receptor agonists and antagonists |
| US20070117835A1 (en) * | 2005-10-04 | 2007-05-24 | David Hung | Methods and compositions for treating Huntington's disease |
| RU2338537C2 (ru) * | 2006-01-25 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670010A1 (de) * | 1966-12-07 | 1970-07-30 | Abbott Lab | Aroylalkylderivate von 1,2,3,4-Tetrahydro-5H-pyride-[4,3b]-indolen und Verfahren zur Herstellung derselben |
| US3522262A (en) * | 1968-09-10 | 1970-07-28 | Hoffmann La Roche | 5-(pyridylalkyl)-pyridoindole derivatives |
| US3502688A (en) * | 1968-09-10 | 1970-03-24 | Hoffmann La Roche | 5-(4-pyridylethyl)-pyridoindole derivatives |
| DE1952800C3 (de) * | 1969-10-20 | 1974-04-18 | Nautschno-Issledowatelskij Institut Farmakologii I Chimioterapii, Moskau | 3,6-Dimethyl-l,2,3,4,4a,9a-hexahydro-gamma-carbolin-dihydrochlorid |
| US4001263A (en) * | 1974-04-01 | 1977-01-04 | Pfizer Inc. | 5-Aryl-1,2,3,4-tetrahydro-γ-carbolines |
| DE2621729A1 (de) * | 1976-05-15 | 1977-12-08 | Boehringer Sohn Ingelheim | Neue 2-(4-phenyl-4-cyanobutyl)-1,2, 3,4-tetrahydro-5(h)-pyrido- eckige klammer auf 4,3-b eckige klammer zu -indole und verfahren zu ihrer herstellung |
| US4224329A (en) * | 1979-01-23 | 1980-09-23 | Pfizer Inc. | 2-Substituted-trans-5-aryl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indoles |
| US4337250A (en) * | 1979-07-30 | 1982-06-29 | Pfizer Inc. | Hexahydro-trans- and tetrahydropyridoindole neuroleptic agents |
| US4672117A (en) * | 1985-09-16 | 1987-06-09 | American Home Products Corporation | Antipsychotic gamma-carbolines |
| DE3851597T2 (de) * | 1987-09-03 | 1995-01-26 | Glaxo Group Ltd., London | Lactamderivate. |
-
1985
- 1985-09-16 US US06/776,180 patent/US4636563A/en not_active Expired - Fee Related
-
1986
- 1986-08-19 ZA ZA866258A patent/ZA866258B/xx unknown
- 1986-08-25 AU AU61813/86A patent/AU590605B2/en not_active Ceased
- 1986-09-02 AT AT86306745T patent/ATE55770T1/de not_active IP Right Cessation
- 1986-09-02 EP EP86306745A patent/EP0223344B1/en not_active Expired - Lifetime
- 1986-09-02 DE DE8686306745T patent/DE3673607D1/de not_active Expired - Fee Related
- 1986-09-03 GB GB8621226A patent/GB2180536B/en not_active Expired
- 1986-09-05 IL IL79956A patent/IL79956A0/xx not_active IP Right Cessation
- 1986-09-05 AR AR86305167A patent/AR242208A1/es active
- 1986-09-08 PH PH34230A patent/PH22515A/en unknown
- 1986-09-08 MX MX368186A patent/MX3681A/es unknown
- 1986-09-10 YU YU1576/86A patent/YU45023B/xx unknown
- 1986-09-10 PT PT83344A patent/PT83344B/pt not_active IP Right Cessation
- 1986-09-11 CA CA000517999A patent/CA1275099A/en not_active Expired - Fee Related
- 1986-09-12 ES ES8601849A patent/ES2002656A6/es not_active Expired
- 1986-09-12 SU SU864028180A patent/SU1442074A3/ru active
- 1986-09-12 GR GR862343A patent/GR862343B/el unknown
- 1986-09-12 FI FI863692A patent/FI83318C/fi not_active IP Right Cessation
- 1986-09-12 JP JP61216964A patent/JPS6267083A/ja active Pending
- 1986-09-13 CN CN86106194A patent/CN1013864B/zh not_active Expired
- 1986-09-15 KR KR1019860007738A patent/KR900002245B1/ko not_active IP Right Cessation
- 1986-09-15 EG EG581/86A patent/EG18015A/xx active
- 1986-09-15 NO NO863671A patent/NO163619C/no unknown
- 1986-09-15 HU HU863942A patent/HU195217B/hu not_active IP Right Cessation
- 1986-09-15 DK DK440686A patent/DK440686A/da not_active Application Discontinuation
- 1986-09-15 NZ NZ217580A patent/NZ217580A/xx unknown
-
1991
- 1991-07-11 HK HK534/91A patent/HK53491A/xx unknown
-
1992
- 1992-04-03 CY CY1595A patent/CY1595A/xx unknown
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