CA1070685A - Morphanthridine derivatives - Google Patents
Morphanthridine derivativesInfo
- Publication number
- CA1070685A CA1070685A CA258,374A CA258374A CA1070685A CA 1070685 A CA1070685 A CA 1070685A CA 258374 A CA258374 A CA 258374A CA 1070685 A CA1070685 A CA 1070685A
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- Prior art keywords
- formula
- compound
- hydrogen
- carbon atoms
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-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Case 500-5386 IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS
Abstract of the Disclosure This invention provides new compounds of formula I, I
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, useful as anti-psychotics and sleep-inducing agents.
Abstract of the Disclosure This invention provides new compounds of formula I, I
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, useful as anti-psychotics and sleep-inducing agents.
Description
~o70685 ,;~. . .
:: `
IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS
The present invention relates to morphanthridine derivatives.
The present invention provides compounds of formula I, ~ ~ N ~
~NJ
:: `
IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS
The present invention relates to morphanthridine derivatives.
The present invention provides compounds of formula I, ~ ~ N ~
~NJ
2 ~ ~ ~ ~ I
CHz wherein Rl is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen.
When Rl is alkyl, it is preferably methyl. When Rl is hydroxyalkyl, this preferably has 2 to 4 carbon atoms. The hydroxy group is preferably bound to the terminal carbon atom away from the nitrogen atom to which Rl is bound. Rl is, for example, ~-hydroxyethyl. Rl is preferably hydrogen or alkyl.
~` When R2 is halogen, it is fluorine, chlorine or bromine, especially fluorine or chlorine.
The present invention also provides a process for the production of a compound of formula I, as defined ~ .
'.' 1 ' O
'' ` ' ` ` 1070685 ' ..
above, whlch comprises reacting a compound of formula II, ,; ' ~
R2 ~ ~ ~ ~ ~ II
~, CH2 ....
wherein R2 ls as deflned above, and X 18 chlorlne, with a co~pound of formula,III, .~-N ~ N-Rl III
1, , .
;- 5wherein Rl is a3 defined above.
The process may be effected ln known manner for ~i ~ 8uch condens ation~.
.. The reaction may be convenlently effected ln an .
i lnert organlc/solvent, for example, xylene o~ dioxane, , .
~'':' .. ' "
.; ~ -~ 2 -.,, . ~ ~ . , ~ .
.
107~85 `: . .. .
. .
at temperature~ between 50 and 170 C, preferably between 100 and lqO C.
The re~ulting compounds of formula I may be l~olated and purlfled ln conventlonal manner, ~:,. s .A compound of formula II, used as startlng material . may be obtained by ..;
. a) reactlng a compound of formula IV, " ., ,. A2 ~ ' ~ ' ? IV
;
O
. .:
r~
;~ wherein R2 18 as deflned above, ,~ with a compound of formula V, ,....
...... .
~f ~ CH3-Mgy V
.. ,;.'~ , . . .
;~. lO whereln Y is chlorine, bromine or lodlne, .
ospeclally bromlne, under conventlonal condltlons for a Grlgnard reactlon, b) hydrolysing the resultlng reactlon complex to glve a :
: . ;
. ~ .~ . .
: .
.,. .
- .
? ,~
. - 3 -',:
. .
.
~ r 1070685 .
. ll-methyl-ll-hydroxy reactlon product, c) dehydratlng the ll-methyl-ll-hydrox~ reactlon product ln conventional manner to give a compound of formula VI, - ~
R ~ NH-Co - 2 ~ VI
, .. .
: , CH2 ,~ .
. . .
whereln R2 is a~ deflned above, and . S d) converting the compound of formula VI ln conventional .1 , .
manner lnto a com*ound of formula II~
Insofar as the preparatlon of any startlng fjl . materlal 18 not partlcularly degcribed, this is known or `. may be produced and purlfled ln known manner or in analogous manner to methods described here$n or ln : analogous manner to known processe~.
: Free base form~ of compound~ of formula I may be converted into a~id addition ~alt ~orm in conventional manner and vlce versa. Suitable acld3 ~or ~alt formation include hydrochloric acld, methane-~ulphonlc acid or .~ maleic acld.
., , ~ .
. ~
_ 4 _ -~ r!~
. ~ ....
.. ....
, 07~685 ~ . . _ . , ;~
, : In the following Examples all temperatures are ... .
... ~ uncorrected and are in degrees Centigrade.
,, ., .
.~
,, .
: '.
:
,',..~ -.
:
:-. _ 5 _ :
-.
EXAMPLE 1~ Methylene-6-(4-methyl~i~erazin-1-yl)-mor~hanthridlne a~ 6-Chloro-ll-methylene-mor~hanthridine _ _ _ _ _ .
8 g of S,6-dihydro-11-methylene-morphanthridin-6-one are boiled for 2 hours with 3 ml of N,N-dimethylaniline and 80 ml of phosphoryl chloride. The resulting dark solution is concentrated in a vacuum. The residue is treated with xylene and once again the mixture is evaporated in a vacuum. The residue is dissolved in 80 ml of xylene and the solution is poured onto ice-water. The mixture is extracted twice with xylene. The xylene extracts are combined, washed in turn with dilute hydrochloric acid, water and a saturated sodium chloride aqueous solution, dried over sodium sulphate and treated with active charcoal. The xylene solution is filtered through aluminium oxide and concentrated to a volume of about 100 to 150 ml in a vacuum. This solution contains 6-chloro-11-methylene-morphanthridine which is used directly in step b).
b) 11 Methylene~6-(4-methyl~i~erazln-~-yl)-mor~hanthridine The xylene solution of 6-chloro~ methylene~morphanthridine is treated with 8 g of N-methylpiperazine and the mixture is boiled for 4 hours. The hydrochloride salt of N-methylpiperazine precipitates out of solution. The mixture is treated with water and 25 ml of a concentrated sodium hydroxide aqueous solution. The organic phase is - shaken twice with ether, washed with water and extracted : with 2N hydrochloric acid.
The acid extract is made alkaline with 2N aqueous sodium hydroxide solution and the resulting oily phase which separates out is extracted twice with ether. The ether extracts are combined,.washed with water and a saturated aqueous sodium chlorlde solution, dried over sodium sulphate, tre.ated with active charcoal and then filtered through aluminium oxide. Recrystallization from ether/petrol.eum ether yields ll-methylene-6-~4-methyl-piperazin-l-yl)-morphanthrldine as prisms; M.Pt. 119 -120.
In analogous manner to that described in Example 1 using the appropriate starting materials of formulae II and III the following compounds of formula I are obtained, wherein:-Ex.No. Rl ~ M.Pt.
2 H H fil90-195oc 1)2) ~208-2lloc 1)3)
CHz wherein Rl is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen.
When Rl is alkyl, it is preferably methyl. When Rl is hydroxyalkyl, this preferably has 2 to 4 carbon atoms. The hydroxy group is preferably bound to the terminal carbon atom away from the nitrogen atom to which Rl is bound. Rl is, for example, ~-hydroxyethyl. Rl is preferably hydrogen or alkyl.
~` When R2 is halogen, it is fluorine, chlorine or bromine, especially fluorine or chlorine.
The present invention also provides a process for the production of a compound of formula I, as defined ~ .
'.' 1 ' O
'' ` ' ` ` 1070685 ' ..
above, whlch comprises reacting a compound of formula II, ,; ' ~
R2 ~ ~ ~ ~ ~ II
~, CH2 ....
wherein R2 ls as deflned above, and X 18 chlorlne, with a co~pound of formula,III, .~-N ~ N-Rl III
1, , .
;- 5wherein Rl is a3 defined above.
The process may be effected ln known manner for ~i ~ 8uch condens ation~.
.. The reaction may be convenlently effected ln an .
i lnert organlc/solvent, for example, xylene o~ dioxane, , .
~'':' .. ' "
.; ~ -~ 2 -.,, . ~ ~ . , ~ .
.
107~85 `: . .. .
. .
at temperature~ between 50 and 170 C, preferably between 100 and lqO C.
The re~ulting compounds of formula I may be l~olated and purlfled ln conventlonal manner, ~:,. s .A compound of formula II, used as startlng material . may be obtained by ..;
. a) reactlng a compound of formula IV, " ., ,. A2 ~ ' ~ ' ? IV
;
O
. .:
r~
;~ wherein R2 18 as deflned above, ,~ with a compound of formula V, ,....
...... .
~f ~ CH3-Mgy V
.. ,;.'~ , . . .
;~. lO whereln Y is chlorine, bromine or lodlne, .
ospeclally bromlne, under conventlonal condltlons for a Grlgnard reactlon, b) hydrolysing the resultlng reactlon complex to glve a :
: . ;
. ~ .~ . .
: .
.,. .
- .
? ,~
. - 3 -',:
. .
.
~ r 1070685 .
. ll-methyl-ll-hydroxy reactlon product, c) dehydratlng the ll-methyl-ll-hydrox~ reactlon product ln conventional manner to give a compound of formula VI, - ~
R ~ NH-Co - 2 ~ VI
, .. .
: , CH2 ,~ .
. . .
whereln R2 is a~ deflned above, and . S d) converting the compound of formula VI ln conventional .1 , .
manner lnto a com*ound of formula II~
Insofar as the preparatlon of any startlng fjl . materlal 18 not partlcularly degcribed, this is known or `. may be produced and purlfled ln known manner or in analogous manner to methods described here$n or ln : analogous manner to known processe~.
: Free base form~ of compound~ of formula I may be converted into a~id addition ~alt ~orm in conventional manner and vlce versa. Suitable acld3 ~or ~alt formation include hydrochloric acld, methane-~ulphonlc acid or .~ maleic acld.
., , ~ .
. ~
_ 4 _ -~ r!~
. ~ ....
.. ....
, 07~685 ~ . . _ . , ;~
, : In the following Examples all temperatures are ... .
... ~ uncorrected and are in degrees Centigrade.
,, ., .
.~
,, .
: '.
:
,',..~ -.
:
:-. _ 5 _ :
-.
EXAMPLE 1~ Methylene-6-(4-methyl~i~erazin-1-yl)-mor~hanthridlne a~ 6-Chloro-ll-methylene-mor~hanthridine _ _ _ _ _ .
8 g of S,6-dihydro-11-methylene-morphanthridin-6-one are boiled for 2 hours with 3 ml of N,N-dimethylaniline and 80 ml of phosphoryl chloride. The resulting dark solution is concentrated in a vacuum. The residue is treated with xylene and once again the mixture is evaporated in a vacuum. The residue is dissolved in 80 ml of xylene and the solution is poured onto ice-water. The mixture is extracted twice with xylene. The xylene extracts are combined, washed in turn with dilute hydrochloric acid, water and a saturated sodium chloride aqueous solution, dried over sodium sulphate and treated with active charcoal. The xylene solution is filtered through aluminium oxide and concentrated to a volume of about 100 to 150 ml in a vacuum. This solution contains 6-chloro-11-methylene-morphanthridine which is used directly in step b).
b) 11 Methylene~6-(4-methyl~i~erazln-~-yl)-mor~hanthridine The xylene solution of 6-chloro~ methylene~morphanthridine is treated with 8 g of N-methylpiperazine and the mixture is boiled for 4 hours. The hydrochloride salt of N-methylpiperazine precipitates out of solution. The mixture is treated with water and 25 ml of a concentrated sodium hydroxide aqueous solution. The organic phase is - shaken twice with ether, washed with water and extracted : with 2N hydrochloric acid.
The acid extract is made alkaline with 2N aqueous sodium hydroxide solution and the resulting oily phase which separates out is extracted twice with ether. The ether extracts are combined,.washed with water and a saturated aqueous sodium chlorlde solution, dried over sodium sulphate, tre.ated with active charcoal and then filtered through aluminium oxide. Recrystallization from ether/petrol.eum ether yields ll-methylene-6-~4-methyl-piperazin-l-yl)-morphanthrldine as prisms; M.Pt. 119 -120.
In analogous manner to that described in Example 1 using the appropriate starting materials of formulae II and III the following compounds of formula I are obtained, wherein:-Ex.No. Rl ~ M.Pt.
2 H H fil90-195oc 1)2) ~208-2lloc 1)3)
3 H0-CH2-CH2- H 151-155C
2 2 Cl 147-149C
H Cl 130-138C
6 CH3 Cl 162-164C
1) decomposition 2) maleate salt form.
3) methane sulphonate salt form The production of the 5,6-dihydro-3-halo-11-methylene-morphanthridin-6-ones used as starting materials of formula IV may be effected as follows_-a) 5 6-dihydro-3-fluoro-morehanthridin-6,11-dione _L_____ ________________ _____________________ A solution o~ 88 g of chromium (VI) trioxide in 60 ml of water is added dropwise over 4 hours to a stirred solution of 5,6-dihydro-3-fluoro-morphanthridin-6-one in 1.5 Iitres of acetic acid warmed to 60C. The mixture is then-heated for 1 hour under reflux, cooled and then poured onto ice-water. The crystals formed are separated off and washed with water. After drying the heading compound M.Pt. 282-285C (sublimation) is obtained.
In analogous manner 3-chloro-5,6-dihydro-morph-anthridin-6,11-dlone is obtained, melting at 293-295~C.
b) 5 6-Dihydro-3-fluoro-11-meth~lene-mor~hanthridin-6-one _L_____ ____ ____ __ __ __ ____ _ __ ___ __ _ ____ ___ ______ __ 150 ml of absolute tetrahydrofuran is added in portions with an exothermic reaction to a Grignard solution of 5.6 g of magnesium, 30.6 g of methyl iodide and 80 ml of ether. The solution is cooled to 10C. In a nitrogen gas atmosphere this solution is treated in small portions . . ~.
.
1C~70685 with a suspension of l9 g of 5,6-dihydro-3-fluoro-morph-anthridin-6,11-dione in 200 ml of absolute tetrahydro-furan. The mixture is stirred for 4 hours at room temperature and then poured onto an ice-cold ammonical ammonium chloride aqueous solution. The mixture is then extracted with ether. The ether extracts are washed with brine and concentrated to dryness. The hard residue containing 5,6-dihydro-3-fluoro~ hydroxy-ll-methyl-morphanthridin-6-one is dissolved in a little acetone, treated with 18 g of pyridine hydrochloride and warmed in the presence of a stream of nitrogen. ~fter the acetone is removed, the mixture is warmed for 90 minutes to 130 - 140C, cooled somewhat, treated with water, separated from the water and dried. After recrystallization lS from acetone/petroleum ether the heading compound melting at 220 - 230C (crystal change from 160C) is obtained.
In analogous manner 3-chloro-5,6-dihydro-ll-methylene-morphanthridin-6-one melting at 247 - 249C
is obtained.
_ g _ .. . - , . , : .
- .
The compounds of formula I exhibit pharmacological activity. In particular, the compounds of formula I (a) inhibit the locomotor activity in mice in a test carried out according to the principles of Caviezel and Baillod, Pharma Acta E~elv. 33, 465-484 (1958), (b) inhibit the arousal reaction of xabbits as determined by electro-encephalography in a test carried out according to the-method of Stille et al., Int. J. Neuropharmacology 4~
375-391 (1965) and/or (c) have a significant effect on the sleep of rats, significantly increasing the deep sleep phase, in a test carried out according to the method of Stille et al, Ps~chopharmacologica 28, 325-337 (1973).
As a result of their activity in tests a) and b) the compounds are therefore indicated for use as anti-psychotics. An indicated daily dose is from about 5 to about 500 mg, conveniently administered in dlvided doses 2 to 4 times a day in unit dosage form containing from about 1 to about 250 mg or in sustained release form.
The compounds of formula I, wherein R2 is halogen, especially the compound of Example 6, exhibits especially interesting activity in tests a) and b).
As result of their activity in test c) the compounds are indicated for use as hypnotics. An indicated daily dose is from about 1 to 100 mg, conveniently administered in a single dose shortly before the time when sleep is required.
The compounds of formula I, wherein R2 is hydrogen, especially the compound of Example 2, exhibit particularly interesting activity in test c).
The compounds of formula I may be administered in pharmaceutically acceptable acid addition salt form.
Such acid addition salt forms exhibit the sam~ order of activity as the free base forms and are readily prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of formula I, in free base form or in pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.
Such cOTnpOSitiOnS may be in the form of, for example, a solution or a tablet.
.
2 2 Cl 147-149C
H Cl 130-138C
6 CH3 Cl 162-164C
1) decomposition 2) maleate salt form.
3) methane sulphonate salt form The production of the 5,6-dihydro-3-halo-11-methylene-morphanthridin-6-ones used as starting materials of formula IV may be effected as follows_-a) 5 6-dihydro-3-fluoro-morehanthridin-6,11-dione _L_____ ________________ _____________________ A solution o~ 88 g of chromium (VI) trioxide in 60 ml of water is added dropwise over 4 hours to a stirred solution of 5,6-dihydro-3-fluoro-morphanthridin-6-one in 1.5 Iitres of acetic acid warmed to 60C. The mixture is then-heated for 1 hour under reflux, cooled and then poured onto ice-water. The crystals formed are separated off and washed with water. After drying the heading compound M.Pt. 282-285C (sublimation) is obtained.
In analogous manner 3-chloro-5,6-dihydro-morph-anthridin-6,11-dlone is obtained, melting at 293-295~C.
b) 5 6-Dihydro-3-fluoro-11-meth~lene-mor~hanthridin-6-one _L_____ ____ ____ __ __ __ ____ _ __ ___ __ _ ____ ___ ______ __ 150 ml of absolute tetrahydrofuran is added in portions with an exothermic reaction to a Grignard solution of 5.6 g of magnesium, 30.6 g of methyl iodide and 80 ml of ether. The solution is cooled to 10C. In a nitrogen gas atmosphere this solution is treated in small portions . . ~.
.
1C~70685 with a suspension of l9 g of 5,6-dihydro-3-fluoro-morph-anthridin-6,11-dione in 200 ml of absolute tetrahydro-furan. The mixture is stirred for 4 hours at room temperature and then poured onto an ice-cold ammonical ammonium chloride aqueous solution. The mixture is then extracted with ether. The ether extracts are washed with brine and concentrated to dryness. The hard residue containing 5,6-dihydro-3-fluoro~ hydroxy-ll-methyl-morphanthridin-6-one is dissolved in a little acetone, treated with 18 g of pyridine hydrochloride and warmed in the presence of a stream of nitrogen. ~fter the acetone is removed, the mixture is warmed for 90 minutes to 130 - 140C, cooled somewhat, treated with water, separated from the water and dried. After recrystallization lS from acetone/petroleum ether the heading compound melting at 220 - 230C (crystal change from 160C) is obtained.
In analogous manner 3-chloro-5,6-dihydro-ll-methylene-morphanthridin-6-one melting at 247 - 249C
is obtained.
_ g _ .. . - , . , : .
- .
The compounds of formula I exhibit pharmacological activity. In particular, the compounds of formula I (a) inhibit the locomotor activity in mice in a test carried out according to the principles of Caviezel and Baillod, Pharma Acta E~elv. 33, 465-484 (1958), (b) inhibit the arousal reaction of xabbits as determined by electro-encephalography in a test carried out according to the-method of Stille et al., Int. J. Neuropharmacology 4~
375-391 (1965) and/or (c) have a significant effect on the sleep of rats, significantly increasing the deep sleep phase, in a test carried out according to the method of Stille et al, Ps~chopharmacologica 28, 325-337 (1973).
As a result of their activity in tests a) and b) the compounds are therefore indicated for use as anti-psychotics. An indicated daily dose is from about 5 to about 500 mg, conveniently administered in dlvided doses 2 to 4 times a day in unit dosage form containing from about 1 to about 250 mg or in sustained release form.
The compounds of formula I, wherein R2 is halogen, especially the compound of Example 6, exhibits especially interesting activity in tests a) and b).
As result of their activity in test c) the compounds are indicated for use as hypnotics. An indicated daily dose is from about 1 to 100 mg, conveniently administered in a single dose shortly before the time when sleep is required.
The compounds of formula I, wherein R2 is hydrogen, especially the compound of Example 2, exhibit particularly interesting activity in test c).
The compounds of formula I may be administered in pharmaceutically acceptable acid addition salt form.
Such acid addition salt forms exhibit the sam~ order of activity as the free base forms and are readily prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of formula I, in free base form or in pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.
Such cOTnpOSitiOnS may be in the form of, for example, a solution or a tablet.
.
Claims (2)
1. A process for the productlon of a compound of formula I, I
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, or a pharmaceuti-cally acceptable acld addition salt thereof, which comprises reacting a compound of formula II , II
wherein R2 is as defined above, and X is chlorine, with a compound of formula III, III
wherein R1 is as defined above, and, if required, converting the resulting compound of formula I into a pharmaceutically acceptable acid addition salt thereof.
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, or a pharmaceuti-cally acceptable acld addition salt thereof, which comprises reacting a compound of formula II , II
wherein R2 is as defined above, and X is chlorine, with a compound of formula III, III
wherein R1 is as defined above, and, if required, converting the resulting compound of formula I into a pharmaceutically acceptable acid addition salt thereof.
2. A novel morphanthridine derivative of the formula:
I
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, or a pharmaceutically acceptable acid addition salt thereof, whenever produced by the process of claim 1 or an obvious chemical equivalent thereof.
I
wherein R1 is hydrogen, alkyl of 1 to 4 carbon atoms, or hydroxyalkyl of 1 to 4 carbon atoms, and R2 is hydrogen or halogen, or a pharmaceutically acceptable acid addition salt thereof, whenever produced by the process of claim 1 or an obvious chemical equivalent thereof.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1024775A CH601287A5 (en) | 1975-08-06 | 1975-08-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1070685A true CA1070685A (en) | 1980-01-29 |
Family
ID=4361070
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA258,374A Expired CA1070685A (en) | 1975-08-06 | 1976-08-04 | Morphanthridine derivatives |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS5219690A (en) |
| AU (1) | AU1661376A (en) |
| BE (1) | BE844881A (en) |
| CA (1) | CA1070685A (en) |
| CH (1) | CH601287A5 (en) |
| DE (1) | DE2633782A1 (en) |
| DK (1) | DK342976A (en) |
| ES (1) | ES450498A1 (en) |
| FI (1) | FI62664C (en) |
| FR (1) | FR2320103A1 (en) |
| GB (1) | GB1551442A (en) |
| GR (1) | GR70677B (en) |
| IE (1) | IE44449B1 (en) |
| IL (1) | IL50198A0 (en) |
| NL (1) | NL7608567A (en) |
| NO (1) | NO145538C (en) |
| NZ (1) | NZ181684A (en) |
| PH (1) | PH11347A (en) |
| PT (1) | PT65435B (en) |
| SE (1) | SE7608519L (en) |
| ZA (1) | ZA764731B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH624682A5 (en) * | 1976-11-10 | 1981-08-14 | Sandoz Ag | |
| DE2918778A1 (en) * | 1979-05-10 | 1980-11-20 | Basf Ag | 6-SUBSTITUTED 11-ALKYLENE MORPHANTRIDINE |
| IT1207417B (en) * | 1982-03-15 | 1989-05-17 | Menarini Sas | AZEPINA-6-ONE WITH ACTIVITIES TRICYCLIC COMPOUNDS DERIVED FROM PHARMACOLOGICAL, AND PROCEDURES OF 5,6-DIHYDRO-11H-DIBENZO (B, E) RELATED MANUFACTURE |
| JPS6266910U (en) * | 1985-10-11 | 1987-04-25 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3389139A (en) * | 1963-06-14 | 1968-06-18 | Wander Ag Dr A | 6-homopiperazino and piperazinomorphanthridines |
| CH436308A (en) * | 1964-05-27 | 1967-05-31 | Wander Ag Dr A | Process for the preparation of 6-basic substituted morphanthridines |
| DE1670053A1 (en) * | 1966-02-18 | 1970-08-13 | Boehringer Mannheim Gmbh | Process for the preparation of new derivatives of morphanthridine |
-
1975
- 1975-08-06 CH CH1024775A patent/CH601287A5/xx not_active IP Right Cessation
-
1976
- 1976-07-28 DE DE19762633782 patent/DE2633782A1/en not_active Withdrawn
- 1976-07-28 SE SE7608519A patent/SE7608519L/en unknown
- 1976-07-28 FI FI762153A patent/FI62664C/en not_active IP Right Cessation
- 1976-07-29 NO NO762644A patent/NO145538C/en unknown
- 1976-07-29 DK DK342976A patent/DK342976A/en unknown
- 1976-08-02 NL NL7608567A patent/NL7608567A/en not_active Application Discontinuation
- 1976-08-04 CA CA258,374A patent/CA1070685A/en not_active Expired
- 1976-08-04 IE IE1723/76A patent/IE44449B1/en unknown
- 1976-08-04 PH PH18752A patent/PH11347A/en unknown
- 1976-08-04 NZ NZ181684A patent/NZ181684A/en unknown
- 1976-08-04 GR GR51411A patent/GR70677B/el unknown
- 1976-08-04 IL IL50198A patent/IL50198A0/en unknown
- 1976-08-04 GB GB32458/76A patent/GB1551442A/en not_active Expired
- 1976-08-04 PT PT65435A patent/PT65435B/en unknown
- 1976-08-04 JP JP51092409A patent/JPS5219690A/en active Pending
- 1976-08-04 BE BE169558A patent/BE844881A/en unknown
- 1976-08-05 ES ES450498A patent/ES450498A1/en not_active Expired
- 1976-08-05 AU AU16613/76A patent/AU1661376A/en not_active Expired
- 1976-08-06 FR FR7624028A patent/FR2320103A1/en active Granted
- 1976-08-06 ZA ZA00764731A patent/ZA764731B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ181684A (en) | 1978-04-28 |
| DK342976A (en) | 1977-02-07 |
| DE2633782A1 (en) | 1977-02-17 |
| IE44449L (en) | 1977-02-06 |
| PT65435B (en) | 1978-05-10 |
| GR70677B (en) | 1982-12-06 |
| BE844881A (en) | 1977-02-04 |
| FI62664B (en) | 1982-10-29 |
| FI62664C (en) | 1983-02-10 |
| NO145538C (en) | 1982-04-14 |
| GB1551442A (en) | 1979-08-30 |
| ZA764731B (en) | 1978-03-29 |
| NO762644L (en) | 1977-02-08 |
| NL7608567A (en) | 1977-02-08 |
| NO145538B (en) | 1982-01-04 |
| SE7608519L (en) | 1977-02-07 |
| FR2320103A1 (en) | 1977-03-04 |
| FI762153A (en) | 1977-02-07 |
| CH601287A5 (en) | 1978-07-14 |
| PH11347A (en) | 1977-11-02 |
| PT65435A (en) | 1976-09-01 |
| AU1661376A (en) | 1978-02-09 |
| JPS5219690A (en) | 1977-02-15 |
| IL50198A0 (en) | 1976-10-31 |
| IE44449B1 (en) | 1981-12-02 |
| ES450498A1 (en) | 1977-12-16 |
| FR2320103B1 (en) | 1978-12-22 |
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