US3699099A - 11-aminoalkylidenemorphanthridines - Google Patents

11-aminoalkylidenemorphanthridines Download PDF

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Publication number
US3699099A
US3699099A US848355A US3699099DA US3699099A US 3699099 A US3699099 A US 3699099A US 848355 A US848355 A US 848355A US 3699099D A US3699099D A US 3699099DA US 3699099 A US3699099 A US 3699099A
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US
United States
Prior art keywords
morphanthridine
compounds
chloro
dimethylaminopropylidene
lower alkyl
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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US848355A
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English (en)
Inventor
Alexander E Drukker
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.)
Colgate Palmolive Co
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Colgate Palmolive Co
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Filing date
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
    • C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the compounds are 11-aminoalkylidenemorphanthridines which are useful as central nervous system depressants, skeletal muscle relaxants and antitremor agents.
  • Representative of the compounds disclosed are 11- (3 dimethylaminopropylidene)morphanthridine and 2- chloro-l 1 (3-dimethylaminopropylidene)morphanthridine.
  • R and R are selected from hydrogen, lower alkyl of 1 to 4 carbon atoms such as methyl, ethyl or isopropyl, a phenyl-lower alkyl of 7 to 13 carbon atoms such as benzyl, phenethyl or phenylisopropyl, a cycloalkyl of 3 to 7 carbon atoms such as cyclopropyl, cyclopentyl and cyclohexyl and cycloalkyl-lower alkyl groups in which the cycloalkyl group contains 3 to 7 carbon atoms such as cyclopentyl-ethyl and cyclohexylmethyl or (b) a heterocyclic amino group such as morpholino, pyrrolidino, piperidino, N-lower alkyl piperazino such as N-methylpiperazino, N-phenyl-lower alkyl piperazino groups such as N-benzyl piperazino and
  • the compounds of the present invention may be conveniently prepared from the corresponding substituted 11- morphanthridones which have the following formula:
  • the compounds are prepared by the reaction of the ll-morphanthridone and an aminoalkylphosphonium compound and a strong base such as butyl lithium.
  • the reaction is preferably carried out in a mutual solvent, such as tetrahydrofuran, at reflux.
  • the reaction is generally complete in about 10 hours and the desired morphanthridine derivative isolated by conventional techniques.
  • EQJHRKCHQ nAm in which R is an alkyl group of 1 to 4 carbon atoms, phenyl, aminophenyl or benzyl, and R n and Am are as defined previously.
  • aminoalkylphosphonium compounds may be prepared as described in U.S. Pat. No. 3,354,155. Representative of such compounds which may be employed are the following:
  • the compounds of the present invention have been found to possess utility as pharmaceutical agents, especially central nervous system depressants and agents for treating Parkinsons disease and drug induced extra pyramidal disorders.
  • central nervous system depressants especially central nervous system depressants and agents for treating Parkinsons disease and drug induced extra pyramidal disorders.
  • the compounds ll-(3-dimethylaminopropylidene)morphanthridine and 2-chloro-11-(3-dimethylaminopropylidene)morphanthridine were found in doses of 10 mg./kg. intraperitoneally to cause centralnervous system depression.
  • the studies also indicated .that the compounds had LD s in excess of 150 mg./ kg. intraperitoneally.
  • Each of the forementioned compounds were also tested for antitremor activity.
  • the compounds were administered to mice in doses of 0.3 to 30 mg./kg. intraperitoneally prior to challenge with oxotremorine.
  • x0- tremorine when administered to normal nonmedicated animals produces a tremor, rigidity, and parasympathomimetic stimulation which very closely resembles the rigidity and tremor of Parkinsons disease.
  • the compounds When employed as pharmaceutical agents the compounds are preferably used in the form of acid addition salts.
  • acid addition salts may be conveniently prepared by conventional means such as by contacting the compounds with a suitable acid in a mutual solvent and then removing the solvent to obtain the desired salt.
  • acids which may be used are hydrochloric acid, succinic acid, tartaric acid, benzoic acid or fu-maric acid.
  • Quaternary ammonium salts of the compounds may be formed by conventional techniques employing a suitable alkylating agent such as methyl chloride, methyl iodide or ethyl bromide.
  • Pharmaceutical dosage forms containing the active ingredients are generally prepared by combining the active ingredients or ingredients with a major amount of one or more suitable pharmaceutical diluents and then forming the resulting mixture into unit dosage forms suitable for oral or parenteral administration.
  • the unit dosage forms will generally contain from 5 to 250 mg. of the active ingredients. One or more of such units may be administered daily depending upon the patients physical size and the severity of the condition being treated. However, generally the daily dosage will not exceed 150 mg. of the active ingredient per kilogram of the patients body weight.
  • composition which may be prepared are the following:
  • the powders, other than magnesium stearate, are granulated with water, passed through a No. 16 mesh screen and dried at 50 C. Magnesium stearate is mixed in and 40 mg. tablets are pressed.
  • Example 3 The process of Example 1 may be repeated using in place of 3 demthylaminopropyltriphenylphosphonium bromide hydrobromide one of the following:
  • Example 2 may be "repeated using in place of 3 dimethylaminopropyltriphenylphosphonium bromide hydrobromide one of the following:
  • a heterocyclic amino group selected from morpholino, pyrrolidino, piperidino, N lower alkyl piperazino, N phenyl lower alkyl piperazino and N-(hydroxy-lower alkyl)-piperazin0.
  • Y is chloro, R is hydrogen and Am is in which R and R are methyl.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
US848355A 1969-08-07 1969-08-07 11-aminoalkylidenemorphanthridines Expired - Lifetime US3699099A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US84835569A 1969-08-07 1969-08-07

Publications (1)

Publication Number Publication Date
US3699099A true US3699099A (en) 1972-10-17

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Family Applications (1)

Application Number Title Priority Date Filing Date
US848355A Expired - Lifetime US3699099A (en) 1969-08-07 1969-08-07 11-aminoalkylidenemorphanthridines

Country Status (8)

Country Link
US (1) US3699099A (enrdf_load_stackoverflow)
JP (1) JPS504675B1 (enrdf_load_stackoverflow)
BE (1) BE753958A (enrdf_load_stackoverflow)
DE (1) DE2035517C3 (enrdf_load_stackoverflow)
ES (1) ES381989A1 (enrdf_load_stackoverflow)
FR (1) FR2060085B1 (enrdf_load_stackoverflow)
GB (1) GB1304069A (enrdf_load_stackoverflow)
ZA (1) ZA704266B (enrdf_load_stackoverflow)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3931158A (en) * 1973-12-06 1976-01-06 Richardson-Merrell Inc. Cis and trans-6-substituted-11-aminoalkylidene-5,6-dihydromorphanthridines
US4388237A (en) * 1979-05-10 1983-06-14 Basf Aktiengesellschaft 6(1-Piperazinyl), piperidino and (1(homopiperazinyl)11-cyanomethylene morphanthridines

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5225585A (en) * 1975-08-22 1977-02-25 Hitachi Ltd Semiconductor device of multilayer distribution structure
DE2918832A1 (de) * 1979-05-10 1980-11-20 Basf Ag 5,6-dihydro-11-alkylen-morphantridin- 6-one
JPS567451A (en) * 1979-06-29 1981-01-26 Hitachi Ltd Semiconductor device
JPS6151961A (ja) * 1984-08-22 1986-03-14 Sanyo Electric Co Ltd 相補型ｍｏｓ半導体装置
US5728894A (en) * 1994-06-22 1998-03-17 Ashahi Kasei Kogyo Kabushiki Kaisha Method for producing methacrolein

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3391136A (en) * 1963-09-13 1968-07-02 Boehringer Sohn Ingelheim 3-chloro-11-(upsilan-dimethylaminopropylidene)-5, 6-dihydromorphanthridine and derivatives
GB1085406A (en) * 1963-10-14 1967-10-04 Pfizer & Co C Aminoalkylphosphorus compounds, preparation thereof and reaction products with ketones

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3931158A (en) * 1973-12-06 1976-01-06 Richardson-Merrell Inc. Cis and trans-6-substituted-11-aminoalkylidene-5,6-dihydromorphanthridines
US4388237A (en) * 1979-05-10 1983-06-14 Basf Aktiengesellschaft 6(1-Piperazinyl), piperidino and (1(homopiperazinyl)11-cyanomethylene morphanthridines

Also Published As

Publication number Publication date
BE753958A (fr) 1971-01-27
FR2060085B1 (enrdf_load_stackoverflow) 1974-03-22
JPS504675B1 (enrdf_load_stackoverflow) 1975-02-22
DE2035517B2 (de) 1979-01-25
DE2035517C3 (de) 1979-09-13
DE2035517A1 (de) 1971-03-25
ZA704266B (en) 1972-02-23
GB1304069A (enrdf_load_stackoverflow) 1973-01-24
ES381989A1 (es) 1973-05-01
FR2060085A1 (enrdf_load_stackoverflow) 1971-06-11

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