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US3699099A - 11-aminoalkylidenemorphanthridines - Google Patents

11-aminoalkylidenemorphanthridines Download PDF

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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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morphanthridine
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chloro
dimethylaminopropylidene
lower alkyl
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Alexander E Drukker
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Colgate Palmolive Co
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    • 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)

Abstract

THE COMPOUNDS ARE 11-AMINOALKYLIDENEOMORPHANTHRIDINES 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 2CHLORO-11(3-DIMETHYLAMINPROPYLIDENE)MORPHANTHRIDINE.

Description

United States Patent 3,699,099 ll-AMINOALKYLIDENEMORPHANTHRIDINES Alexander E. Drukker, Milwaukee, Wis., assignor to Colgate-Palmolive Company, New York, N.Y.
No Drawing. Filed Aug. 7, 1969, Ser. No. 848,355 Int. Cl. C07d 41/08, 57/00 U.S. Cl. 260-239 D Claims ABSTRACT OF THE DISCLOSURE 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.
DESCRIPTION OF THE INVENTION The compounds of the present invention may be represented by the following formula:
in which 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 N-(hydroxy-lower alkyl)-piperazino groups such as Hp-hydroxyethyl) piperazino.
The compounds of the present invention may be conveniently prepared from the corresponding substituted 11- morphanthridones which have the following formula:
in which X and Y are as previously defined. These compounds are known compounds and may be prepared as described by R. G. Cooke and I. M. Russell. Tetrahedron Letters, 1968 (44), 4587-8.
Patented Oct. 17, 1972 ice Representative of the compounds that may be ememployed are:
1 l-morphanthridone,
2-chloro-1 l-morphanthridone, Z-fluoro-l l-morphanthridone, 3-chloro-1 l-morphanthridone, Z-trifiuoromethyl- 1 l-morphanthridone, 2-methoxy-1 l-morphanthridone, Z-thiomethyl-l l-morphanthridone, Z-methyl-l l-morphanthridone, 8-methyl- 1 l-morphanthridone, and 9-methyl-l l-morphanthridone.
In the preferred practice of the present invention 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.
The described process may be illustrated as follows:
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.
The 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:
3-dimethylaminopropyltriphenylphosphonium bromide hydrobromide,
3- l-piperazinopropyl triphenylphosphonium bromide hydrobromide,
3-(4-hydroxyethyl-l-piperazinopropyl)triphenylphosphonium bromide hydrobromide,
3-diethylaminopropyltriphenylphosphonium bromide hydrobromide, and
3-methylaminopropyltriphenylphosphonium bromide hydrobromide.
Representative of the compounds which may be pared by the described process are the following:
pre-
1 l- 3-dimethylaminopropylidene) morphanthridine,
2-chloro-1 1-(3-dimethy1aminopropylidene)morphanthridine,
2-trifluoromethyl-1 1- (3-dimethylaminopropylidene) morphanthridine,
1 1- 3-piperazinopropylidene) morphanthridine,
2-chloro-1 l- 3 -piperazinopropylidene morphanthridine,
2-trifluoromethyl-1 1-( 3-piperazinopropylidene) morphanthridine,
1 1- 3- (4-hydroxyethylpiperazinopropylidene) morphanthridine,
2-chloro-1 1- [3-(4-hydroxyethylpiperazinopropylidene) morphanthridine,
'2-trifluoromethyl- 1 l- [3- 4-hydroxyethylpiperazinopropylidene) morphanthridine,
1 1-( 3-diethylaminopropylidene morphanthridine,
2-chloro-11-(3-diethylaminopropylidene)morphanthridine,
Z-trifiuoromethyl-l l- (3-diethylaminopropylidene) morphanthridine,
1 1- 3-methylaminopropylidene)morphanthridine,
2-chloro-1 1- (3-methylaminopropylidene morphanthridine, and
Z-trifluoromethyl-l l-( 3-methylaminopropylidene) morphanthridine.
The final compounds exist as both the cis and trans isomers which are separable.
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. In mouse behavioral studies 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. In the tests 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 similarity of 0x0- tremorine induced behavior in animals to that seen in Parkinsons disease in man, coupled with the fact that all agents found to be useful in treating Parkinsons disease also blocked the eifects of oxotremorine in animals, has lead to the general use of oxotremorine in the screening of drugs for anti-Parkinsonism activity. Animals pretreated -with 8 mg./ kg. of the above mentioned compounds were completely protected from the effects of 0x0- thremorine challenge. The test indicated that the compounds had an antitremor ED of about 4 mg./ kg. intraperitoneally. Significantly the blockade of the oxotremorine eifects was accomplished at dose levels which produced very little in the way of undesirable side eifects such as mydriasis.
When employed as pharmaceutical agents the compounds are preferably used in the form of acid addition salts. Such 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. Examples of 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.
4 Representative of a suitable pharmaceutical 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.
The practice of the invention is further illustrated by the following examples:
EXAMPLE 1 l 1- 3 -dimethylaminopropylidene )morph anthridine To a cooled slurry of 16.4 g. (0.032 mole) of 3-dimethylaminopropyltriphenylphosphonium bromide hydrobromide in 50 ml. of tetrahydrofuran is added with stirring 0.064 mole of butyl lithium solution. The mixture is stirred 1 hour at room temperature, cooled, and 4.97 (0.029 mole of 11 morphanthridone in 25 ml. of tetrahydrofuran added dropwise. The solution is stirred for 1.5 hours at room temperature, refluxed for 10 hours, cooled, 20 ml. of Water added and the mixture concentrated. The residue is treated with dilute aqueous hydrochloric acid and benzene, and the aqueous layer separated and made alkaline with potassium hydroxide. The resulting oil is extracted into ether, dried over potassium carbonate, filtered, concentrated, and distilled to yield 11-(3- dimethylaminopropylidene)morphanthridine, B.P. 188- 200 (0.05 mm.). This base is then converted to the biscyclohexylsulfamate, :M.P. 11-6-117.
Analysis.-Calcd. for C H N O S (percent): C, 58.64; H, 7.30; N, 8.82. Found (percent): C, 58.90; H,
EXAMPLE 2 Z-chloro-l 1- 3-dimethylaminopropylidene) morphanthridine To a cooled slurry of 5.1 g. (0.01 mole) of 3-dimethyl-,
aminopropyltriphenylphosphonium bromide hydrobromide in 20 ml. of tetrahydrofuran is added with stirring 0.02 mole of butyl lithium solution. The mixture is stirred 1 hour at room temperature, cooled, and 1.9 g. (0.0079 mole) of 2 chloro ll-morphanthridone (M.P. 130.5 in 20 ml. of tetrahydrofuran added dropwise. The solution is stirred for 1.5 hours at room temperature, refluxed for 11 hours, cooled, 7 ml. of water added, and the mixture is then concentrated. Theresidue is treated-with dilute cold hydrochloric acid and benzene, the aqueous layer separated, made alkaline with potassium hydroxide, and extracted with ether. The ethereal extracts are dried over potassium carbonate, filtered, and concentrated and the residue distilled to yield 2 chloro 11-(3-dimethylaminopropylidene)morphanthridine as a viscous oil, B.P. 180-200 (0.05 mm.). This oil is chromatographed over silica gel using benzene-methanol (ratio 4:1) as eluent. Fractions totaling 0.77 g. were collected and redistilled to afford 2 chloro 11 (3 dimethylaminopropylidene) morphanthridine as a yellow viscous base.
Analysis.-Calcd. for C H ClN (percent): C, 73.18; H,'6.46; N, 8.99. Found (percent): C, 73.30; H, 6.62;
EXAMPLE 3 The process of Example 1 may be repeated using in place of 3 demthylaminopropyltriphenylphosphonium bromide hydrobromide one of the following:
3-( l-piperazinopropyl) triphenylphosphonium bromide hydrobromide,
3-(4-hydroxyethyl-l-piperazinopropyl)triphenylphosphonium bromide hydrobromide,
3-diethylaminopropyltriphenylphosphonium bromide hydrobromide, and
3-methylaminopropyltriphenylphosphonium bromide hydrobromide, respectively to obtain 1 l-(3-piperazinopropylidene) morphanthridine, 1 1- [3- (4-hydroxyethylpiperazinopropylidene) morphanthridine, 1 1- 3-diethylaminopropylidene morphanthridine, and 1 1- 3-methylaminopropylidene morphanthridine,
respectively.
- EXAMPLE 4 The process of Example 2 may be "repeated using in place of 3 dimethylaminopropyltriphenylphosphonium bromide hydrobromide one of the following:
3-( l-piperazinopropyl) triphenylphosphonium bromide hydrobromide,
3-(4-hydroxyethyl-l-piperazinopropyl)triphenylphosphoniumbromide hydrobromide,
3-diethylaminopropyltriphenylphosphonium bromide hydrobromide, and
3-methylaminopropyltriphenylphosphonium bromide hydrobromide, respectively to obtain 2-chloro-1 1-(3-piperazinopropylidene)morphanthridine,
2-chloro-11-[3-(4-hydroxyethylpiperazinopropylidene) morphanthridine,
2-chloro-11-(3-diethylaminopropylidene) morphanthridine, and
2-chloro-l1-(3-methylaminopropylidene) morphanthridine, respectively.
I claim: 1. A compound selected from compounds and acid addition salts of compounds of the formula HCHR (CH2)nAm in which X and Y are members of the group consisting of hydrogen, halogen, lower alkoxy, lower alkyl, thiolower alkyl and trifluoromethyl, R is hydrogen or lower alkyl, 1; is to 4 and Am is selected from R: in which R and R are selected from hydrogen, lower alkyl, phenyl-lower alkyl of 7 to 13 carbon atoms, cycloalkyl of 3 to 7 carbon atoms and cycloalkyl-lower alkyl in which the cycloalkyl contains 3 to 7 carbon atoms, or
(b) a heterocyclic amino group selected from morpholino, pyrrolidino, piperidino, N lower alkyl piperazino, N phenyl lower alkyl piperazino and N-(hydroxy-lower alkyl)-piperazin0.
2. A compound of claim 1 in which Am is in which R and R are methyl.
7. A compound of claim 1 in which X is hydrogen,
Y is chloro, R is hydrogen and Am is in which R and R are methyl.
8. A compound of the formula H R R 9 CHI H-CHn-C Hr-N wherein R and R are hydrogen or chlorine.
9. 11-(3-dimethylaminopropylidene)morphanthridine. 10. 2 chloro l1 (3 dimethylaminopropylidene) morphanthridine.
References Cited Chemical Abstracts Subject Index, vol. 64, p. 2188s (1966).
Thomae: Chemical Abstracts, vol. 64, cols. 19575- 19576 (1966).
ALTON D. ROLLINS, Primary Examiner U.S. Cl. X.R.
260-240 TC, 268 R, 268 K, 570.5 R; 424-244, 248, 267, 274
US848355A 1969-08-07 1969-08-07 11-aminoalkylidenemorphanthridines Expired - Lifetime US3699099A (en)

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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 (en) * 1979-05-10 1980-11-20 Basf Ag 5,6-DIHYDRO-11-ALKYLENE-MORPHANETRIDINE-6-ONE
JPS567451A (en) * 1979-06-29 1981-01-26 Hitachi Ltd Semiconductor device
JPS6151961A (en) * 1984-08-22 1986-03-14 Sanyo Electric Co Ltd Complementary type mos semiconductor device
DE69513172T2 (en) * 1994-06-22 2000-08-24 Asahi Kasei Kogyo K.K., Osaka 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
GB1085405A (en) * 1963-10-14 1967-10-04 Pfizer & Co C Dibenzoxepins and dibenzthiepins

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

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FR2060085A1 (en) 1971-06-11
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DE2035517B2 (en) 1979-01-25
DE2035517C3 (en) 1979-09-13
JPS504675B1 (en) 1975-02-22
ES381989A1 (en) 1973-05-01
GB1304069A (en) 1973-01-24
DE2035517A1 (en) 1971-03-25
ZA704266B (en) 1972-02-23

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