EP0000395A1 - 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
EP0000395A1
EP0000395A1 EP78100365A EP78100365A EP0000395A1 EP 0000395 A1 EP0000395 A1 EP 0000395A1 EP 78100365 A EP78100365 A EP 78100365A EP 78100365 A EP78100365 A EP 78100365A EP 0000395 A1 EP0000395 A1 EP 0000395A1
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EP
European Patent Office
Prior art keywords
carbon atoms
formula
compounds
alkoxy
atoms
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
EP78100365A
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German (de)
English (en)
Other versions
EP0000395B1 (fr
Inventor
Max-Peter Dr. Seiler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sandoz AG
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Sandoz AG
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Publication date
Application filed by Sandoz AG filed Critical Sandoz AG
Publication of EP0000395A1 publication Critical patent/EP0000395A1/fr
Application granted granted Critical
Publication of EP0000395B1 publication Critical patent/EP0000395B1/fr
Expired legal-status Critical Current

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Classifications

    • 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 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.
  • the method b) can be used for the splitting of Aethern known manner.
  • the cleavage is conveniently 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.
  • 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.
  • Hydrogen chloride is preferably carried out at a pressure of 1 to 10 atm. If X, Y or Z represent 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
  • 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 be carried out 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 formula I 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
  • solutions of the formula VI can lead directly to compounds of the formula Ia if the reaction is carried out under reducing conditions.
  • hydrogen can be used as the reducing agent in the presence of catalysts such as Raney nickel, platinum or palladium-carbon.
  • catalysts such as Raney nickel, platinum or palladium-carbon.
  • the process is expediently carried out in a solvent, for example acetic acid, 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 I.
  • medicaments which contain a compound of the formula I.
  • These remedies For example, a solution or a tablet can be prepared by known methods using the usual auxiliaries and carriers.
  • the amine is released from the 1st mother liquor of the (-) - mandelic acid salt described above by extraction with sodium carbonate solution / methylene chloride and using (+) - mandelic acid, analogously to the for (-) - mandelic acid, the (-) - antipode of the title compound is produced, the hydrochloride of which melts at 263-265 ° after recrystallization from methanol.

Landscapes

  • 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)
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
CH1358377 1977-11-08
CH13583/77 1977-11-08

Publications (2)

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

Family

ID=25703869

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100365A Expired EP0000395B1 (fr) 1977-07-18 1978-07-11 Dérivés de 2-pipérazinotétraline, leur préparation et leur utilisation comme médicament

Country Status (17)

Country Link
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)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4590274A (en) * 1985-01-03 1986-05-20 E. I. Du Pont De Nemours And Company Antihypertensive 1-[bis-(substituted phenyl)methyl]-4[2-(1,2,3,4-tetrahydro-substituted naphthalen-1-ylidene)ethyl]piperazines
WO1987002035A1 (fr) * 1985-10-04 1987-04-09 Maggioni-Winthrop S.P.A. Aminoalcools cycloaliphatiques fusionnes
US4826975A (en) * 1986-06-25 1989-05-02 Maggioni-Winthrop S.P.A. Fused cycloaliphatic aminoalcohols
US4845221A (en) * 1988-04-15 1989-07-04 American Home Products Corporation Serotonergic substituted piperazinyl tetralins
EP0343830A2 (fr) * 1988-05-23 1989-11-29 Eli Lilly And Company 2-Amino-1,2,3,4-tétrahydronaphthalènes substitués dans l'anneau
EP0395244A1 (fr) * 1989-04-07 1990-10-31 JOHN WYETH & BROTHER LIMITED Dérivés de pyridine
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

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL85700A0 (en) * 1987-03-24 1988-08-31 Takeda Chemical Industries Ltd 1,4-disubstituted piperazine compounds,their production and use
US4988699A (en) * 1989-03-14 1991-01-29 Warner-Lambert Company Substituted tetrahydrobenzothiazoles as dopaminergic agents

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1190466B (de) * 1961-11-07 1965-04-08 Cassella Farbwerke Mainkur Ag Verfahren zur Herstellung von Piperazinderivaten
FR2100935A1 (fr) * 1970-07-20 1972-03-24 Richardson Merrell Spa
FR2323388A1 (fr) * 1975-09-15 1977-04-08 Squibb & Sons Inc Nouveaux phenylpiperazinotetrahydronaphtols, leur preparation et leur utilisation therapeutique comme hypotenseurs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1190466B (de) * 1961-11-07 1965-04-08 Cassella Farbwerke Mainkur Ag Verfahren zur Herstellung von Piperazinderivaten
FR2100935A1 (fr) * 1970-07-20 1972-03-24 Richardson Merrell Spa
FR2323388A1 (fr) * 1975-09-15 1977-04-08 Squibb & Sons Inc Nouveaux phenylpiperazinotetrahydronaphtols, leur preparation et leur utilisation therapeutique comme hypotenseurs

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4590274A (en) * 1985-01-03 1986-05-20 E. I. Du Pont De Nemours And Company Antihypertensive 1-[bis-(substituted phenyl)methyl]-4[2-(1,2,3,4-tetrahydro-substituted naphthalen-1-ylidene)ethyl]piperazines
WO1987002035A1 (fr) * 1985-10-04 1987-04-09 Maggioni-Winthrop S.P.A. Aminoalcools cycloaliphatiques fusionnes
US4826975A (en) * 1986-06-25 1989-05-02 Maggioni-Winthrop S.P.A. Fused cycloaliphatic aminoalcohols
US4845221A (en) * 1988-04-15 1989-07-04 American Home Products Corporation Serotonergic substituted piperazinyl tetralins
EP0343830A2 (fr) * 1988-05-23 1989-11-29 Eli Lilly And Company 2-Amino-1,2,3,4-tétrahydronaphthalènes substitués dans l'anneau
EP0343830A3 (en) * 1988-05-23 1990-11-28 Eli Lilly And Company Ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes
EP0395244A1 (fr) * 1989-04-07 1990-10-31 JOHN WYETH & BROTHER LIMITED Dérivés de pyridine
US5075303A (en) * 1989-04-07 1991-12-24 John Wyeth & Brother Limited Pyridine 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

Also Published As

Publication number Publication date
FI68821C (fi) 1985-11-11
CA1131641A (fr) 1982-09-14
US4308266A (en) 1981-12-29
CY1224A (en) 1984-04-06
DK309678A (da) 1979-01-19
ES479059A1 (es) 1979-07-01
IE781438L (en) 1979-01-18
IT1105089B (it) 1985-10-28
IE47129B1 (en) 1983-12-28
JPS5422383A (en) 1979-02-20
IT7850272A0 (it) 1978-07-13
NZ187876A (en) 1981-02-11
IL55153A0 (en) 1978-09-29
AU521642B2 (en) 1982-04-22
HK85184A (en) 1984-11-16
FI68821B (fi) 1985-07-31
PT68306A (fr) 1978-08-01
FI782202A (fi) 1979-01-19
EP0000395B1 (fr) 1981-01-07
DE2860410D1 (en) 1981-02-26
IL55153A (en) 1983-07-31
ES471809A1 (es) 1979-10-01
AU3808678A (en) 1980-01-17
PH17238A (en) 1984-07-03

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