US3359263A - Nu-substituted-1-phenyl-2-aminopropanes - Google Patents

Nu-substituted-1-phenyl-2-aminopropanes Download PDF

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Publication number
US3359263A
US3359263A US302707A US30270763A US3359263A US 3359263 A US3359263 A US 3359263A US 302707 A US302707 A US 302707A US 30270763 A US30270763 A US 30270763A US 3359263 A US3359263 A US 3359263A
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US
United States
Prior art keywords
phenyl
dibenzo
dihydro
ylidene
ethyl
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.)
Expired - Lifetime
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US302707A
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English (en)
Inventor
Stelt Cornelis Van Der
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.)
Koninklijke Pharmaceutische Fabrieken NV
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Koninklijke Pharmaceutische Fabrieken NV
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Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
    • C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/90—Xanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • R is lower alkyl (e.g., methyl, ethyl); R is selected from the group consisting of hydrogen, halogen (e.g., chloro, bromo, fluoro) and lower alkyl (e.
  • novel compounds of this invention are physiologically useful and possess coronary blood vessel dilating activity and may be employed in treatment of such conditions as coronary disease, the dosage being adjusted to the patients needs and the relative potency of the compound employed.
  • the invention includes within its scope pharmaceutical preparations containing one or more of the therapeutically active compounds of this invention, or non-toxic acid addition salts thereof, in association with a pharmacologically acceptable carrier.
  • the preparation may take any of the forms customarily employed for administration of therapeutically active substances but the preferred types are those suitable for oral administration and especially tablets, pills, and capsules including the substance.
  • the tablets and pills may be formulated in manner, known per se with one or more pharmacologically acceptable diluents or excipients such as lactose or starch, and include materials of a lubricating nature such as calcium stearate.
  • Capsules made of absorbable material may contain the active substance alone or in admixture with a.solid or liquid diluent.
  • Liquid preparations may be in the form of suspensions, emulsions, syrups or elixirs of the active substance in water or other liquid medium commonly used for making orally acceptable pharmaceutical formulations, such as liquid paralfin, or a syrup or elixir base.
  • the active substance may also be made up in a form suitable for parenteral administration, i.e., as a suspension or emulsion in sterile water or an organic liquid usually employed for injectable preparations, for example vegetable oil such as olive oil, or a sterile solution in an organic solvent.
  • the compounds of this invention may be employed directly or in the form of their physiologically acceptable non-toxic acid addition salts, i.e., salts which are not harmful to the animal organism when used in therapeutic doses, derived from inorganic acids such .as the hydrohalic acids, for example, hydrochloric or hydrobromic acid, and from organic acids, such as citric maleic, fumaric, tartaric and succinic acids.
  • physiologically acceptable non-toxic acid addition salts i.e., salts which are not harmful to the animal organism when used in therapeutic doses, derived from inorganic acids such .as the hydrohalic acids, for example, hydrochloric or hydrobromic acid, and from organic acids, such as citric maleic, fumaric, tartaric and succinic acids.
  • the preferred compounds of this invention are those wherein R is hydrogen, Y is lower alkylene (e.g., ethylene) when n is 1, and Z is CH CH.
  • the most preferable compounds of this invention are N-[2-(l(l,l1-dihydro-SH-dibenzo [a,d] cyclohepten-S-yDethyl]-l-phenyl-2- aminopropane and N-[2-(fiuoren-9-ylidene)ethy1]-1-phenyI-Z-aminoprop-ane and the pharmaceutically acceptable nontoxic acid addition salts thereof.
  • the compounds of this invention may be prepared according to the processes of this invention, by first reacting a 1-phenyl-aminoalkane, for example, dl-l-phenyl- Z-aminopropane or dl-l-phenyl-Z-aminobutane, with an aldehyde of the general formulawherein Y, n and R are as hereinbefore defined to yield a compound of the formula wherein R, R, Y and n are as hereinbefore defined.
  • a 1-phenyl-aminoalkane for example, dl-l-phenyl- Z-aminopropane or dl-l-phenyl-Z-aminobutane
  • R, R, Y and n are as hereinbefore defined.
  • the aldehydes employed as starting materials may be prepared by condensing a ketone of the formula wherein R, Y and n are as hereinbefore defined, under the influence of a condensing agent such 'as sodamide with acetylene in a medium of liquid ammonia to yield an acetylenic compound of the formula HCEC and causing isomerization of the acetylenic compound by treatment with acid to give aldehydes of the general formula set forth hereinabove.
  • Acid addition salts of the compounds of this invention may be prepared by methods known per se.
  • the base may be treated with the equivalent quantity of the acid in an inert solvent such as diethyl ether.
  • a one litre flask is fitted with a dropping-funnel, a gas-inlet tube filled with solid potassium hydroxide, and a condenser to the upper end of which a tube filled with solid potassium hydroxide is attached. Flask and condenser are cooled with solid carbon dioxide in acetone. From a gas cylinder a quantity of about 200-250 ml. of ammonia is condensed into the flask through the tube filled with potassium hydroxide. Another flask, fitted with an inlet tube nearly reaching to the bottom, an outlet tube and an ascending tube is filled with water.
  • the inlet tube is connected with two washing-bottles placed in series and filled with concentrated sulphuric acid and, moreover, with a tower filled with glass-wool.
  • the latter system is connected with a supply of nitrogen gas.
  • the air is completely replaced by nitrogen by bubbling same through the system.
  • the nitrogen supply is switched off and a stream of acetylene gas passed through the flask containing water to remove acetone vapor stemming from the acetone soaked diatom aceous earth, wherein the acetylene is dissolved in the cylinder.
  • the outlet of the tower is then connected with the inlet tube of the flask, containing the liquid ammonia. 0.2 g.
  • the 9-l'luorenylidene acetaldehyde used as a starting material can be prepared from fluorenone in the following way.
  • R is lower alkyl
  • R is selected from the group consisting of hydrogen, halogen, and lower alkyl
  • Y is selected from the group consisting of oxygen and sulfur

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
US302707A 1962-10-19 1963-08-16 Nu-substituted-1-phenyl-2-aminopropanes Expired - Lifetime US3359263A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB39753/62A GB1006588A (en) 1962-10-19 1962-10-19 N-substituted-1-phenyl-2-aminopropanes

Publications (1)

Publication Number Publication Date
US3359263A true US3359263A (en) 1967-12-19

Family

ID=10411293

Family Applications (1)

Application Number Title Priority Date Filing Date
US302707A Expired - Lifetime US3359263A (en) 1962-10-19 1963-08-16 Nu-substituted-1-phenyl-2-aminopropanes

Country Status (12)

Country Link
US (1) US3359263A (en, 2012)
BE (1) BE638839A (en, 2012)
BR (1) BR6353836D0 (en, 2012)
CH (1) CH455754A (en, 2012)
DE (1) DE1214688B (en, 2012)
DK (2) DK109925C (en, 2012)
ES (1) ES292867A1 (en, 2012)
FI (2) FI42543B (en, 2012)
FR (2) FR1450391A (en, 2012)
GB (1) GB1006588A (en, 2012)
NL (2) NL133997C (en, 2012)
SE (1) SE313301B (en, 2012)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3442949A (en) * 1965-05-03 1969-05-06 Merck & Co Inc Method for preparing 5-(3-aminopropylidene)-5h-dibenzo - (a,d) - 10,11 - dihydrocycloheptenes
US3480624A (en) * 1964-06-01 1969-11-25 Rhone Poulenc Sa Dibenzocycloheptatriene derivatives
US4464301A (en) * 1981-02-10 1984-08-07 Groupement D'interet Economique Centre International De Recherches Dermatologiques C.I.R.D. 1,8-Dihydroxy-9-anthrones derivatives substituted in the 10-position by an unsaturated radical and their use in human and veterinary medicine
WO1997046549A1 (en) * 1996-06-05 1997-12-11 Novartis Ag Anti-neurodegeneratively effective xanthene derivatives

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4267192A (en) * 1980-03-11 1981-05-12 American Home Products Corporation Method for treating inflammation

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE630063A (en, 2012) * 1962-03-23
US2676971A (en) * 1951-04-21 1954-04-27 Searle & Co Quaternary ammonium derivatives of aminoalkylxanthenes and aminoalkylthiaxanthenes
US3073847A (en) * 1959-02-12 1963-01-15 Hoffmann La Roche 9-(3-amino-1-propynyl) derivatives of 9-xanthenols and 9-thioxanthenols and a process for their preparation
US3177209A (en) * 1960-09-16 1965-04-06 Kefalas As Dihydroanthracene compounds
US3258459A (en) * 1962-08-30 1966-06-28 Squibb & Sons Inc Method for the preparation of n-monosubstituted-secondary aminoalkyl derivatives of polycyclic compounds
US3258488A (en) * 1963-08-12 1966-06-28 Colgate Palmolive Co Dibenzo[a, d]cycloheptene derivatives
US3264342A (en) * 1963-05-24 1966-08-02 Geigy Chem Corp Derivatives of 5h-dibenzo[a, d] cycloheptene

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2676971A (en) * 1951-04-21 1954-04-27 Searle & Co Quaternary ammonium derivatives of aminoalkylxanthenes and aminoalkylthiaxanthenes
US3073847A (en) * 1959-02-12 1963-01-15 Hoffmann La Roche 9-(3-amino-1-propynyl) derivatives of 9-xanthenols and 9-thioxanthenols and a process for their preparation
US3177209A (en) * 1960-09-16 1965-04-06 Kefalas As Dihydroanthracene compounds
BE630063A (en, 2012) * 1962-03-23
US3256332A (en) * 1962-03-23 1966-06-14 Kefalas As Method for the production of 5 (3'-aminopropylidene) dibenzo [a, d] cyclohepta [1, 4] dienes
US3258459A (en) * 1962-08-30 1966-06-28 Squibb & Sons Inc Method for the preparation of n-monosubstituted-secondary aminoalkyl derivatives of polycyclic compounds
US3264342A (en) * 1963-05-24 1966-08-02 Geigy Chem Corp Derivatives of 5h-dibenzo[a, d] cycloheptene
US3258488A (en) * 1963-08-12 1966-06-28 Colgate Palmolive Co Dibenzo[a, d]cycloheptene derivatives

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3480624A (en) * 1964-06-01 1969-11-25 Rhone Poulenc Sa Dibenzocycloheptatriene derivatives
US3442949A (en) * 1965-05-03 1969-05-06 Merck & Co Inc Method for preparing 5-(3-aminopropylidene)-5h-dibenzo - (a,d) - 10,11 - dihydrocycloheptenes
US4464301A (en) * 1981-02-10 1984-08-07 Groupement D'interet Economique Centre International De Recherches Dermatologiques C.I.R.D. 1,8-Dihydroxy-9-anthrones derivatives substituted in the 10-position by an unsaturated radical and their use in human and veterinary medicine
WO1997046549A1 (en) * 1996-06-05 1997-12-11 Novartis Ag Anti-neurodegeneratively effective xanthene derivatives

Also Published As

Publication number Publication date
SE313301B (en, 2012) 1969-08-11
DE1214688B (de) 1966-04-21
NL299449A (en, 2012)
BE638839A (en, 2012)
FR3974M (en, 2012) 1966-03-07
GB1006588A (en) 1965-10-06
FI42543B (en, 2012) 1970-06-01
NL133997C (en, 2012)
CH455754A (de) 1968-05-15
BR6353836D0 (pt) 1973-07-12
ES292867A1 (es) 1964-04-01
DK109925C (da) 1968-08-05
FR1450391A (fr) 1966-06-24
FI44241B (en, 2012) 1971-06-30
DK111174B (da) 1968-06-24

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