EP0000013A1 - 4-Phényl-8-amino-tetrahydroisoquinoléines, compositions pharmaceutiques les contenant et procédé pour préparer ces compositions - Google Patents

4-Phényl-8-amino-tetrahydroisoquinoléines, compositions pharmaceutiques les contenant et procédé pour préparer ces compositions Download PDF

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Publication number
EP0000013A1
EP0000013A1 EP78100025A EP78100025A EP0000013A1 EP 0000013 A1 EP0000013 A1 EP 0000013A1 EP 78100025 A EP78100025 A EP 78100025A EP 78100025 A EP78100025 A EP 78100025A EP 0000013 A1 EP0000013 A1 EP 0000013A1
Authority
EP
European Patent Office
Prior art keywords
amino
acid
tetrahydroisoquinolines
phenyl
hydrogen
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
EP78100025A
Other languages
German (de)
English (en)
Other versions
EP0000013B1 (fr
Inventor
Karl Dr. Schmitt
Irmgard Dr. Hoffmann
Ulrich Dr. Schacht
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.)
Hoechst AG
Original Assignee
Hoechst AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hoechst AG filed Critical Hoechst AG
Publication of EP0000013A1 publication Critical patent/EP0000013A1/fr
Application granted granted Critical
Publication of EP0000013B1 publication Critical patent/EP0000013B1/fr
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine

Definitions

  • DOS 1 795 829 are 4-phenyl-8-amino-tetrahydroisoquinolines of the general formula I. wherein R 1 is hydrogen, a lower alkyl or the benzyl group, R 2 is hydrogen, the methyl group, chlorine or fluorine atoms, R 2 'is hydrogen, methyl, methoxy, hydroxyl or halogen atoms, R 3 and R 4 are hydrogen or a lower alkyl group and R 5 is hydrogen, a chlorine atom or a methoxy group in the 5- or 6-position, known.
  • R 1 is hydrogen, a lower alkyl or the benzyl group
  • R 2 is hydrogen, the methyl group, chlorine or fluorine atoms
  • R 2 ' is hydrogen, methyl, methoxy, hydroxyl or halogen atoms
  • R 3 and R 4 are hydrogen or a lower alkyl group
  • R 5 is hydrogen, a chlorine atom or a methoxy group in the 5- or 6-position, known.
  • the invention therefore relates to compounds of the general formula II in which either R 1 is bromine and R 2 is hydrogen or both R 1 and R 2 are chlorine.
  • the new compounds of the general formula II are characterized inter alia by by an increased effect in the serotonin uptake inhibition test compared to the previously known class of compounds. While the previously known compounds of the formula I (with the exception of compounds of the formula II) only inhibit serotonin uptake in higher concentrations, the compounds of the formula II bring about an inhibition of serotonin uptake which was not previously possible with the compounds of the formula I. could achieve.
  • the inhibition of serotonin uptake manifests itself in an increased emotional mood-enhancing effect and is therefore of considerable importance for therapy.
  • the compounds of formula II are therefore valuable pharmaceuticals which are used for the treatment of depressive states.
  • the compounds of the formula II are prepared by the process of German patent 1,670,694 by cyclization of the corresponding N- (2-aminobenzyl) - ⁇ -methylaminomethyl-benzyl alcohols.
  • the compounds of formula II can form salts with either one or two equivalents of an acid.
  • physiologically acceptable acids are suitable for salt formation.
  • suitable inorganic acids are: hydrohalic acids, such as hydrochloric acid and hydrobromic acid, and also sulfuric acid, phosphoric acid and amidosulfonic acid.
  • organic acids formic acid, acetic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, maleic acid, succinic acid, tartaric acid, benzoic acid, salicylic acid, citric acid, acetic acid or oxyethanesulfonic acid.
  • the base is again prepared from the hydrochloride and is isolated with methylene chloride as an oil (18 g).
  • the carbonyl and nitro groups are then hydrogenated in succession.
  • the carbonyl group gives 15 g of the hydroxy compound with sodium borohydride (5 g in 50 ml methanol to 18 g acetophenone derivative in 250 ml methanol), the nitro group is now hydrogenated with Raney nickel at normal pressure and room temperature.
  • the hydrogen uptake is as calculated, 14 g of N-2-aminobenzyl- ⁇ -N-methylamino-methyl-3,4-dichlorobenzyl alcohol are obtained as an oily product.
  • the base is dissolved with maleic acid (3 g for 8 g base) in ethanol with heating.
  • the maleinate that crystallizes on cooling is recrystallized from ethanol.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Psychiatry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP78100025A 1977-06-01 1978-06-01 4-Phényl-8-amino-tetrahydroisoquinoléines, compositions pharmaceutiques les contenant et procédé pour préparer ces compositions Expired EP0000013B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19772724610 DE2724610A1 (de) 1977-06-01 1977-06-01 4-phenyl-8-amino-tetrahydroisochinoline
DE2724610 1977-06-01

Publications (2)

Publication Number Publication Date
EP0000013A1 true EP0000013A1 (fr) 1978-12-20
EP0000013B1 EP0000013B1 (fr) 1980-10-15

Family

ID=6010350

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78100025A Expired EP0000013B1 (fr) 1977-06-01 1978-06-01 4-Phényl-8-amino-tetrahydroisoquinoléines, compositions pharmaceutiques les contenant et procédé pour préparer ces compositions

Country Status (17)

Country Link
US (1) US4185105A (fr)
EP (1) EP0000013B1 (fr)
JP (1) JPS543078A (fr)
AT (1) AT361482B (fr)
AU (1) AU517664B2 (fr)
CA (1) CA1093079A (fr)
DE (2) DE2724610A1 (fr)
DK (1) DK242278A (fr)
EG (1) EG13777A (fr)
ES (1) ES470226A1 (fr)
FI (1) FI781717A (fr)
HU (1) HU176978B (fr)
IL (1) IL54810A0 (fr)
IT (1) IT1094899B (fr)
NO (1) NO781896L (fr)
PT (1) PT68123A (fr)
ZA (1) ZA783122B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT384806B (de) * 1982-06-04 1988-01-11 Egyt Gyogyszervegyeszeti Gyar Verfahren zur herstellung von neuen 4-aryl-2-methyl-1,2,3,4-tetrahydro-isochinolinderivaten und deren salzen
AU2011202113B2 (en) * 2003-06-10 2012-03-15 Resmed Limited Multiple Stage Blower and Enclosure Therefor

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4340600A (en) * 1980-05-22 1982-07-20 Smithkline Corporation Renal dilating methods and compositions using 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines
DE3310878A1 (de) * 1983-03-25 1984-09-27 Hoechst Ag, 6230 Frankfurt Optische antipoden von 8-amino-4-phenyl-1,2,3,4-tetrahydroisochinolin, verfahren zu ihrer herstellung und sie enthaltende arzneimittel mit antidepressiver wirkung
BG45572A1 (en) * 1986-10-23 1989-07-14 Druzhestven N Izsledovatelski Antiulcer means

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3384640A (en) * 1966-03-15 1968-05-21 Bristol Myers Co Amino isoquinolinium salts
DE1670694B2 (de) * 1966-05-05 1976-07-22 Hoechst Ag, 6000 Frankfurt Verfahren zur herstellung von tetrahydroisochinolinen

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Keine Entgegenhaltungen *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT384806B (de) * 1982-06-04 1988-01-11 Egyt Gyogyszervegyeszeti Gyar Verfahren zur herstellung von neuen 4-aryl-2-methyl-1,2,3,4-tetrahydro-isochinolinderivaten und deren salzen
AU2011202113B2 (en) * 2003-06-10 2012-03-15 Resmed Limited Multiple Stage Blower and Enclosure Therefor

Also Published As

Publication number Publication date
ES470226A1 (es) 1979-01-01
IL54810A0 (en) 1978-07-31
DK242278A (da) 1978-12-02
CA1093079A (fr) 1981-01-06
NO781896L (no) 1978-12-04
JPS543078A (en) 1979-01-11
DE2860212D1 (en) 1981-01-22
AT361482B (de) 1981-03-10
AU517664B2 (en) 1981-08-20
PT68123A (en) 1978-06-01
EG13777A (en) 1982-03-31
AU3670578A (en) 1979-12-06
US4185105A (en) 1980-01-22
EP0000013B1 (fr) 1980-10-15
HU176978B (hu) 1981-06-28
IT7823996A0 (it) 1978-05-30
DE2724610A1 (de) 1978-12-14
FI781717A (fi) 1978-12-02
ZA783122B (en) 1979-06-27
ATA395078A (de) 1980-08-15
IT1094899B (it) 1985-08-10

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