WO1980000251A1 - Derivatives of 2-amino-6,7-dihydroxytetrahydronaphthalene(adtn) - Google Patents

Derivatives of 2-amino-6,7-dihydroxytetrahydronaphthalene(adtn) Download PDF

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Publication number
WO1980000251A1
WO1980000251A1 PCT/US1979/000434 US7900434W WO8000251A1 WO 1980000251 A1 WO1980000251 A1 WO 1980000251A1 US 7900434 W US7900434 W US 7900434W WO 8000251 A1 WO8000251 A1 WO 8000251A1
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WO
WIPO (PCT)
Prior art keywords
formula
amino
derivatives
adtn
tetrahydronaphthalene
Prior art date
Application number
PCT/US1979/000434
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English (en)
French (fr)
Inventor
D Stout
Original Assignee
American Hospital Supply Corp
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 American Hospital Supply Corp filed Critical American Hospital Supply Corp
Priority to DE7979900876T priority Critical patent/DE2965841D1/de
Publication of WO1980000251A1 publication Critical patent/WO1980000251A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/64—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Definitions

  • This invention relates to derivatives of 2-amino-6,7-dihy- droxytetrahydronaphthalene (ADTN) and, more particularly, to N-arylalkyl derivatives of 2-amino-6,7-dihydroxytetrahydro- naphthalene (ADTN) characterized by formula (I)
  • R is OH, alkyloxy, hydroxyalkyl or acyloxy
  • R 1 is an arylalkyl where the aryl group is benzyl, substituted benzyl, phenyl or substituted phenyl and the alkyl group is a straight or branched chain alkyl having one to twenty carbon atoms; and the pharmaceutically acceptable salts thereof.
  • alkyloxy refers to oxygenated straight or branched chain radicals containing one to ten carbon atoms, as illustrated by, but not limited to, methoxy, ethoxy, butoxy and the like.
  • hydroxyalkyl refers to hydroxyl- ated straight or branched chain radicals containing one to ten carbon atoms, as illustrated by, but not limited to 2-propanol, 3-propanol and the like.
  • aryl refers to benzyl, substituted benzyl, phenyl and substituted phenyl where the substituents of benzyl and phenyl include loweralkyl, hydroxy, alkoxy, acyloxy and the like.
  • alkyl refers to straight and branched chain alkyl radicals having from one to twenty carbon atoms such as methyl, n-amyl, 3-methyl-2-octyl, 2-nonyl and 2-tetradecyl.
  • acyloxy refers to acetoxy, pro- pionyloxy, butyrylojcy and the like.
  • salts refers to acid addition salts prepared by reactiny the basic amines of this invention with an organic or inorganic acid, or by reacting the amine salts with the salt of an appropriate acid.
  • Representative salts which are so formed include the hydrochloride, hydrobromide, sulfate, bisulfate, acetate, oleate, laurate, benzoate, phosphate, citrate, maleate, succinate, tartrate and napsylate salts of the amines.
  • the present compounds i.e., N-arylalkyl derivatives of 2-amino-6,7-dihydroxytetrahydronaphthalene (ADTN) may be prepared by reductive aminations of the protected (ADTN) which may be prepared by a modification of the preparation reported by J. G. Cannon et al. (J. Med. Chem., 20, p. 1111 (1977)) and as illustrated in Scheme I below.
  • the preparation of the present derivatives by reductive aminations of the protected (ADTN) is carried out with the appropriate ketones and aldehydes.
  • ADTN reductive aminations of the protected
  • a solution of 2-amino-6,7-dimethoxy -1,2,3,4- tetrahydronaphthalene (VI) in dry methanol is treated with the appropriate ketone or aldehyde and NaCNBH, under a nitrogen atmosphere.
  • the mixture is then stirred for 72 hours whereupon concentrated HCl is added dropwise until the mixture becomes acidic.
  • the methanol is removed on a rotary evaporator and the mixture is extracted with ether.
  • the aqueous mixture is made basic to a pH greater than 12.0 with solid KOH and the mixture is extracted with ether.
  • the combined extracts are dried (MgSO 4 ) and the solvent is removed on a rotary evaporator.
  • the products are dissolved in CHCl 3 and hydrogen chloride is bubbled in and the solvent removed on a rotary evaporator.
  • the products are crystallized in isopropanol and then isolated.
  • the compounds of the present invention that can be prepared by the reductive aminations of the protected (ADTN) and represented by formula (I) include:
  • the compounds of the present invention exhibit inotropic activity in warm-blooded animals at a dosage ranging from about
  • Cardioselectivity* (means ⁇ SEM) Inotropic Selectivity* (means ⁇ SEM)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/US1979/000434 1978-07-14 1979-06-18 Derivatives of 2-amino-6,7-dihydroxytetrahydronaphthalene(adtn) WO1980000251A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE7979900876T DE2965841D1 (en) 1978-07-14 1979-06-18 2-alpha-methyl-dopaminimino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, its salts, and a process for preparation thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US92476378A 1978-07-14 1978-07-14
US924763 1997-08-27

Publications (1)

Publication Number Publication Date
WO1980000251A1 true WO1980000251A1 (en) 1980-02-21

Family

ID=25450688

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1979/000434 WO1980000251A1 (en) 1978-07-14 1979-06-18 Derivatives of 2-amino-6,7-dihydroxytetrahydronaphthalene(adtn)

Country Status (4)

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EP (1) EP0016148B1 (US20020095090A1-20020718-M00002.png)
JP (1) JPS639500B2 (US20020095090A1-20020718-M00002.png)
DE (1) DE2965841D1 (US20020095090A1-20020718-M00002.png)
WO (1) WO1980000251A1 (US20020095090A1-20020718-M00002.png)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981003491A1 (en) * 1980-05-29 1981-12-10 Astra Laekemedel Ab Therapeutically useful tetralin derivatives
WO1982004042A1 (en) * 1981-05-11 1982-11-25 Folke Lars Erik Arvidsson Therapeutically useful tetralin derivatives iii,processes for preparation and pharmaceutical preparations for such compounds
EP0466662A2 (en) * 1990-06-15 1992-01-15 Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. 6,7-disubstituted-2-aminotetralines active as immunomodulators and pharmaceutical compositions containing same

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE745314C (de) * 1941-03-15 1944-11-27 Troponwerke Dinklage & Co Verfahren zur Herstellung von analgetisch wirkenden 1-Oxyphenyl-3-aminoalkylverbindungen
US3135797A (en) * 1958-04-15 1964-06-02 Colgate Palmolive Co Aromatic amino antispasmodic compounds
US3579582A (en) * 1967-02-16 1971-05-18 Universal Oil Prod Co Hydroxy and/or hydrocarbyloxy and amino substituted tetrahydronaphthalenes
US3930022A (en) * 1972-07-03 1975-12-30 Squibb & Sons Inc Certain tetrahydronaphthalenes used in the treatment of cardiac arrhythmia
US4010202A (en) * 1974-04-25 1977-03-01 Takeda Chemical Industries, Ltd. 5,6-Dihydroxy aminotetralol compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2752659A1 (de) * 1976-12-07 1978-06-08 Sandoz Ag Neue tetralinderivate, ihre herstellung und verwendung

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE745314C (de) * 1941-03-15 1944-11-27 Troponwerke Dinklage & Co Verfahren zur Herstellung von analgetisch wirkenden 1-Oxyphenyl-3-aminoalkylverbindungen
US3135797A (en) * 1958-04-15 1964-06-02 Colgate Palmolive Co Aromatic amino antispasmodic compounds
US3579582A (en) * 1967-02-16 1971-05-18 Universal Oil Prod Co Hydroxy and/or hydrocarbyloxy and amino substituted tetrahydronaphthalenes
US3930022A (en) * 1972-07-03 1975-12-30 Squibb & Sons Inc Certain tetrahydronaphthalenes used in the treatment of cardiac arrhythmia
US4010202A (en) * 1974-04-25 1977-03-01 Takeda Chemical Industries, Ltd. 5,6-Dihydroxy aminotetralol compounds

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BURGER "Medicinal Chemistry", 2nd Ed. published 1960, by Interscience Publishers, Inc., pages 596-597. *
Chem. Pharm. Bull Volume 25, No. 11, issued 1977, KATSUMI ITOH et al., "The Synthesis and B-Adrenoceptor Activities of N-Substituted 2-Amino-5, 6-dihydroxy-1,2,3,4,-tetrahydro-1-Naphthenols", see pages 2917-2928. *
Journal Chemical Society (London), (C) Organic, No. 4, issued 1967, R.I. THRIFT, "Derivatives of 2-Aminotetralin", pages 288-293. *
Proc. Natl. Acad. Sci. U.S.A., Volume 74, No. 8, issued 1977, August, VOLKMAN et al., "Conformational Requirements for dopamine-induced vasodilation", see pages 3602-3606. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981003491A1 (en) * 1980-05-29 1981-12-10 Astra Laekemedel Ab Therapeutically useful tetralin derivatives
WO1982004042A1 (en) * 1981-05-11 1982-11-25 Folke Lars Erik Arvidsson Therapeutically useful tetralin derivatives iii,processes for preparation and pharmaceutical preparations for such compounds
EP0466662A2 (en) * 1990-06-15 1992-01-15 Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. 6,7-disubstituted-2-aminotetralines active as immunomodulators and pharmaceutical compositions containing same
EP0466662A3 (en) * 1990-06-15 1992-12-09 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. 6,7-disubstituted-2-aminotetralines active as immunomodulators and pharmaceutical compositions containing same

Also Published As

Publication number Publication date
DE2965841D1 (en) 1983-08-18
EP0016148B1 (en) 1983-07-13
JPS639500B2 (US20020095090A1-20020718-M00002.png) 1988-02-29
EP0016148A1 (en) 1980-10-01
EP0016148A4 (en) 1980-10-13
JPS55500419A (US20020095090A1-20020718-M00002.png) 1980-07-10

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