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EP0000395B1 - Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament - Google Patents

Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament Download PDF

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Publication number
EP0000395B1
EP0000395B1 EP78100365A EP78100365A EP0000395B1 EP 0000395 B1 EP0000395 B1 EP 0000395B1 EP 78100365 A EP78100365 A EP 78100365A EP 78100365 A EP78100365 A EP 78100365A EP 0000395 B1 EP0000395 B1 EP 0000395B1
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Prior art keywords
carbon atoms
alkoxy
hydroxy
compounds
group
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EP78100365A
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German (de)
English (en)
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EP0000395A1 (fr
Inventor
Max-Peter Dr. Seiler
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Sandoz AG
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Sandoz AG
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/88—Nitrogen atoms, e.g. allantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon 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
    • 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
    • C07D295/096—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 separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
    • C07D317/66—Nitrogen atoms not forming part of a nitro radical

Definitions

  • the invention relates to new 2-piperazinotetralins.
  • 2-Piperazinotetralins are already known from German publication 1,190,466, which are unsubstituted in the benzene ring of the tetralin structure. Furthermore, French patent specification 2,100,935 describes derivatives of 2-piperazino-dihydronaphthalene.
  • the compounds of the formula I can occur in the form of enantiomers or in the form of racemates.
  • the compounds of the formula I obtained according to the invention may be in the form of the free bases or their acid addition salts.
  • the free bases can be converted into their acid addition salts in a manner known per se and vice versa.
  • the compounds of formula I according to the invention can e.g. form acid addition salts with inorganic acids such as hydrochloric acid or with organic acids such as maleic acid.
  • Process a) can be carried out in a manner known per se, e.g. by catalytic hydrogenation.
  • Suitable catalysts include palladium-carbon, platinum or Raney nickel, preferably palladium-carbon.
  • An inert organic solvent e.g. Ethanol or dimethylformamide.
  • the reduction can also be carried out with complex metal hydrides, e.g. Sodium borohydride, in an organic solvent such as trifluoroacetic acid.
  • the process is expediently carried out at temperatures between 10 and 50 ° C., preferably 20 and 30 ° C.
  • Process b) can be carried out in a manner known for the cleavage of ethers.
  • the cleavage is advantageously carried out by the action of cleaving agents, for example hydroiodic acid, hydrobromic acid or hydrochloric acid, preferably in water or acetic acid, advantageously at temperatures from 0 to 100 °, or boron tribromide, preferably in methylene chloride, advantageously from 0 to 50 ° C.
  • the pressure is preferably from 1 to 10 atm. If X, Y or Z are alkoxy groups in positions 2 and 6 of the phenyl ring, these are largely retained when using hydrohalic acids and are not converted to free OH groups.
  • the condensation c) can be carried out according to methods known per se for the production of the piperazine ring.
  • the compounds III and IV are preferably heated in an inert solvent at temperatures between 60 and 120 °.
  • the solvent used is advantageously ethanol, dimethylformamide or higher alcohols.
  • the condensation can in the presence of a base, e.g. tert. Amine or alkali carbonate.
  • the radicals Q and Q ' are preferably chlorine, bromine, iodine, an alkylsulfonyloxy or arylsulfonyloxy group.
  • Process d) can be carried out in a manner known for the acylation of phenols.
  • Acid halides or acid anhydrides, for example, can be used as reactive derivatives of the carboxylic acids.
  • the compounds of the formula can be isolated and purified in a manner known per se.
  • optically active compounds of formula I can e.g. starting from optically active starting materials (prepared by methods customary per se for the cleavage of racemates).
  • the compounds of formula II can be obtained by, for example, compounds of formula V with compounds of formula VI implements.
  • the reaction can be carried out in a manner known per se.
  • the reaction can be carried out in an inert solvent, e.g. Toluene, in the presence of catalytic amounts of p-toluenesulfonic acid with water separation, suitably at the reflux temperature of the solvent used or in the presence of catalytic amounts of a Lewis acid, e.g. Titanium tetrachloride, conveniently between 20 and 100 °.
  • an inert solvent e.g. Toluene
  • p-toluenesulfonic acid with water separation suitably at the reflux temperature of the solvent used or in the presence of catalytic amounts of a Lewis acid, e.g. Titanium tetrachloride, conveniently between 20 and 100 °.
  • a Lewis acid e.g. Titanium tetrachloride
  • reaction of compounds of the formula V with compounds of the formula VI can lead directly to compounds of the formula Ia if the reaction is carried out under reducing conditions.
  • a reducing agent e.g. Hydrogen can be used in the presence of catalysts such as Raney nickel, platinum or palladium-carbon.
  • the process is conveniently carried out in a solvent, e.g. Acetic acid, carried out at room temperature.
  • the compounds of the formulas III, IV, V and VI are either known or can be prepared in a manner known per se.
  • the compounds of formula I are distinguished by interesting pharmacodynamic properties.
  • a unit dose for example a tablet suitable for oral administration, can contain between 4 and 500 mg of the active ingredient together with suitable pharmaceutically indifferent auxiliaries.
  • the invention also relates to medicaments which contain a compound of the formula.
  • These remedies for example a solution or a tablet, can be prepared by known methods using the customary auxiliaries and carriers.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Claims (13)

1. Nouveaux composés de formula I
Figure imgb0055
dans laquelle
R1 signifie un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 20 atomes de carbone ou un groupe
Figure imgb0056
où R4 et R5 signifient, indépendamment l'un de l'autre, l'hydrogène, le fluor, le chlore, le brome, l'iode, un groupe alkyle contenant de 1 à 4 atomes de carbone ou alcoxy contenant de 1 à 4 atomes de carbone, ou bien
R4 et R5 sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylenedioxy,
R2 et R3 signifient, indépendamment l'un de l'autre, l'hydrogène, un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 20 atomes de carbone, ou un groupe
Figure imgb0057
ou bien
R, et R2 sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy,
A signifie
a) un groupe
Figure imgb0058
où, X, Y et Z signifient, indépendamment les uns des autres, l'hydrogène, un groupe hydroxy, alkyle contenant de 1 à 4 atomes de carbone, alcoxy contenant de 1 à 4 atomes de carbone, alcartoyloxy contenant de 1 à 20 atomes de carbone, un groupe
Figure imgb0059
le fluor, le chlore, le brome, l'iode, CF3, SH, un groupe alkylthio contenant de 1 à 4 atomes de carbone ou alcanoylthio contenant de 1 à 20 atomes de carbone, ou
X et Y sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy,
D signifie 0 ou S,
b) un groupe
Figure imgb0060
c) un cycle à 5 ou 6 chaînons de formule
Figure imgb0061
où V est soit bivalent et représente 0, S, NH ou CH2, soit trivalent et représente N ou CH, W est une chaîne alkylène saturée ou insaturée contenant 2 ou 3 atomes de carbone, et le cycle @ peut contenir 1, 2 ou 3 doubles liaisons,

ainsi que leurs sels d'addition d'acides.
2. Composés selon la revendication 1, dans lesquels R1 signifie un groupe hydroxy.
3. Composés selon la revendication 1 ou 2, dans lesquels R1 se trouve en position 6.
4. Composés selon la revendication 1, 2 ou 3, dans lesquels R2 et R3 signifient l'hydrogène.
5. Composés selon l'une des revendications 1 à 4, dans lesquels A signifie un groupe
Figure imgb0062
6. Composés selon l'une des revendications 1 à 5, dans lesquels X représente un groupe alkyle ou alcoxy.
7. Composés selon l'une des revendications 1 à 6, dans lesquels X se trouve en position 2 du reste phényle.
8. Le 1,2,3,4-tétrahydro-6-hydroxy-2-[4-(2-méthylphényl)piperazinyl-1]naphtalène ainsi que ses sels d'addition d'acides.
9. Le 1,2,3,4-tétrahydro-6-hydroxy-2-[4-(2-méthoxyphényl)pipérazinyl-1 ]naphtalène ainsi que ses sels d'addition d'acides.
10. Composés selon la revendication 1, dans lesquels
R1 signifie un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 4 atomes de carbone ou benzoyloxy,
R2 et R3 signifient, indépendamment l'un de l'autre, l'hydrogène, un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 4 atomes de carbone ou benzoyloxy, ou bien
R1 et R2 sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy,
A signifie un groupe
Figure imgb0063
où, X, Y et Z signifient, indépendamment les uns des autres, l'hydrogène, un groupe hydroxy, alkyle contenant de 1 à 4 atomes de carbone, alcoxy, contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 4 atomes de carbone, benzoyloxy, le fluor, le chlore ou CF3, ou bien X et Y sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy.
11. Composés selon la revendication 1, dans lesquels R1 signifie un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 20 atomes de carbone ou un groupe
Figure imgb0064
où R4 et R5 signifient, indépendamment l'un de l'autre, l'hydrogène, le fluor, le chlore, le brome, l'iode, un groupe alkyle contenant de 1 à 4 atomes de carbone ou alcoxy contennant de 1 à 4 atomes de carbone, ou bien
R4 et R5 sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy,
R2 et R3 signifient, indépendamment l'un de l'autre, l'hydrogène, un groupe hydroxy, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 20 atomes de carbone ou un groupe
Figure imgb0065
 ou bien
R, et R2 sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy,
A signifie un groupe
Figure imgb0066
où X, Y et Z signifient, indépendamment les uns des autres, l'hydrogène, un groupe hydroxy, alkyle contennant de 1 à 4 atomes de carbone, alcoxy contenant de 1 à 4 atomes de carbone, alcanoyloxy contenant de 1 à 20 atomes de carbone, un groupe
Figure imgb0067
le fluor, le chlore, le brome, l'iode, CF3, SH ou un groupe alkylthio contenant de 1 à 4 atomes de carbone, ou bien
X et Y sont situés sur des atomes de carbone adjacents et forment ensemble un groupe méthylènedioxy.
12. Procédé pour la préparation des composés de formule 1 et de leurs sels d'addition d'acides selon la revendication 1, caractérisé en ce que
a) pour préparer les composés de formule la
Figure imgb0068
dans laquelle R'1 représente un groupe alcoxy contenant de 1 à 4 atomes de carbone,
R'2 et R3 représentent, indépendamment l'un de l'autre, l'hydrogène ou un groupe alcoxy contenant de 1 à 4 atomes de carbone, ou bien
R'1et R'2 forment ensemble un groupe -0-CH2 0- et A' a les mêmes significations que A, à l'exception du reste phényle substitué par au moins un groupe alcanoyloxy, alcanoylthio ou
Figure imgb0069
on réduit des composés de formule Il
Figure imgb0070
b) pour préparer les composés de formule Ib
Figure imgb0071
dans laquelle R''2 et R''3 représentent, indépendamment l'un de l'autre, l'hydrogène ou un groupe hydroxy, et A" représente un groupe
Figure imgb0072
où X', Y' et Z' représentent, indépendamment les uns des autres, l'hydrogène, un groupe hydroxy, alkyle contenant de 1 à 4 atomes de carbone, le fluor, le chlore, le brome, l'iode, CF3 ou SH, ou bien possède l'une des significations données pour A sous b) et c),
on scinde le groupe éther des composés de formule la,
c) pour préparer les composés de formule Ic
Figure imgb0073
dans laquelle R'''1représente un groupe hydroxy ou alcoxy contenant de 1 à 4 atomes de carbone, R'''2 et RI" représentent, indépendamment l'un de l'autre, l'hydrogène, un groupe hydroxy ou alcoxy contenant de 1 à 4 atomes de carbone, on condense des composés de formule III
Figure imgb0074
avec des composés de formule IV
Figure imgb0075
dans laquelle Q et Q' représentent le reste acide d'un ester réactif,
d) pour préparer les composés de formule I où l'un au moins des substituants R1, R2, R3, X, Y ou Z représente un groupe alcanoyloxy ou
Figure imgb0076
et/ou l'un des substituants X, Y ou Z représente un groupe alcanoylthio ou
Figure imgb0077
on acyle les composés de formule I où l'un au moins des substituants Rl, R2, R3, X, Y ou Z représente un groupe hydroxy libre et/ou l'un des substituants X, Y ou Z représente un groupe SH libre, avec un dérivé réactif d'un acide alcanoîque contenant de 1 à 20 atomes de carbone ou d'un acide carboxylique aromatique de formule
Figure imgb0078
et on transforme éventuellement les composés de formule I ainsi obtenus en leurs sels d'addition d'acides.
13. Un médicament contenant au moins un composé selon la revendication 1.
EP78100365A 1977-07-18 1978-07-11 Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament Expired EP0000395B1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH8863/77 1977-07-18
CH886377 1977-07-18
CH13583/77 1977-11-08
CH1358377 1977-11-08

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EP0000395A1 EP0000395A1 (fr) 1979-01-24
EP0000395B1 true EP0000395B1 (fr) 1981-01-07

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US (1) US4308266A (fr)
EP (1) EP0000395B1 (fr)
JP (1) JPS5422383A (fr)
AU (1) AU521642B2 (fr)
CA (1) CA1131641A (fr)
CY (1) CY1224A (fr)
DE (1) DE2860410D1 (fr)
DK (1) DK309678A (fr)
ES (2) ES471809A1 (fr)
FI (1) FI68821C (fr)
HK (1) HK85184A (fr)
IE (1) IE47129B1 (fr)
IL (1) IL55153A (fr)
IT (1) IT1105089B (fr)
NZ (1) NZ187876A (fr)
PH (1) PH17238A (fr)
PT (1) PT68306A (fr)

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JPH01503777A (ja) * 1985-10-04 1989-12-21 マツジヨ‐ニ‐ウインスロツプ・ソチエタ・ペル・アチオニ 縮合脂環式アミノアルコール類
GB8615560D0 (en) * 1986-06-25 1986-07-30 Maggioni Farma Aminoalcohols
IL85700A0 (en) * 1987-03-24 1988-08-31 Takeda Chemical Industries Ltd 1,4-disubstituted piperazine compounds,their production and use
US4845221A (en) * 1988-04-15 1989-07-04 American Home Products Corporation Serotonergic substituted piperazinyl tetralins
CA1335591C (fr) * 1988-05-23 1995-05-16 James Arthur Nixon Derives de subtitution sur le cycle de 2-amino-1,2,3,4-tetrahydronaphtalenes
US4988699A (en) * 1989-03-14 1991-01-29 Warner-Lambert Company Substituted tetrahydrobenzothiazoles as dopaminergic agents
GB8907865D0 (en) * 1989-04-07 1989-05-24 Wyeth John & Brother Ltd Tetrahydroquinoline derivatives
US5194439A (en) * 1990-04-06 1993-03-16 John Wyeth & Brother Limited N-(2,3-dihydro-1,4-benzodioxinyl)-N-substituted aminopyrido-fused cycloalkanes
GB2290790A (en) * 1994-06-30 1996-01-10 Merck & Co Inc Asymmetric synthesis of 6-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes

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DE1190466B (de) * 1961-11-07 1965-04-08 Cassella Farbwerke Mainkur Ag Verfahren zur Herstellung von Piperazinderivaten
CA969955A (en) * 1970-07-20 1975-06-24 Rene Viterbo Dihydronaphthalene derivatives
US4018773A (en) * 1975-09-15 1977-04-19 E. R. Squibb & Sons, Inc. Phenylpiperazinotetrahydronaphthols and derivatives

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EP0000395A1 (fr) 1979-01-24
IE781438L (en) 1979-01-18
CY1224A (en) 1984-04-06
IL55153A (en) 1983-07-31
NZ187876A (en) 1981-02-11
ES479059A1 (es) 1979-07-01
IT1105089B (it) 1985-10-28
FI68821C (fi) 1985-11-11
FI782202A (fi) 1979-01-19
IE47129B1 (en) 1983-12-28
DE2860410D1 (en) 1981-02-26
IL55153A0 (en) 1978-09-29
AU521642B2 (en) 1982-04-22
AU3808678A (en) 1980-01-17
JPS5422383A (en) 1979-02-20
FI68821B (fi) 1985-07-31
PT68306A (fr) 1978-08-01
PH17238A (en) 1984-07-03
US4308266A (en) 1981-12-29
HK85184A (en) 1984-11-16
ES471809A1 (es) 1979-10-01
IT7850272A0 (it) 1978-07-13
CA1131641A (fr) 1982-09-14
DK309678A (da) 1979-01-19

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