GB1589776A - Tetrabenzocycloheptenes - Google Patents
Tetrabenzocycloheptenes Download PDFInfo
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- GB1589776A GB1589776A GB37900/77A GB3790077A GB1589776A GB 1589776 A GB1589776 A GB 1589776A GB 37900/77 A GB37900/77 A GB 37900/77A GB 3790077 A GB3790077 A GB 3790077A GB 1589776 A GB1589776 A GB 1589776A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- 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
- A61P25/24—Antidepressants
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- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
(54) TETRAHYDROBENZOCYCLOHEPTENES (71) We, SANDOZ LTD., of 35 Lichtstrasse, 4002 Basle, Switzerland, a
Swiss Body Corporate, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to 5,6,8,9-tetIahydro--7H-benzocycloheptenes.
More particularly, this invention provides compounds of formula I,
wherein
R1 is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35,
R2 is hydrogen or, when R1 is alkoxy of 1 to 4 carbon atoms, also alkoxy of 1 to 4 carbon atoms, or
R1 and R2 when bonded to adjacent carbon atoms together form a methylenedioxy group,
R, is hydrogen or alkyl of 1 to 4 carbon atoms,
R4 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or, when R3 is alkyl of 1 to 4 carbon atoms, may also be benzyl or benzyl monosubstituted in the phenyl residue by chlorine, bromine, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, or
R3 and R4 together with the nitrogen atom to which they are bound form a pyrrolidine, piperidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of which is substituted by alkyl of 1 to 4 carbon atoms, and Z is
wherein,
either R, is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, trifluoromethyl or halogen of atomic number from 9 to 35, and RG is hydrogen, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35, or R5 and Rc when bonded to adjacent carbon atoms together form a methylenedioxy group, and R7 is hydrogen, alkyl of 1 to 4 carbon atoms or halcgen of atomic number from 9 to 35.
When a substituent in the compounds of formula I is alkyl, alkoxy or alkylthio, these preferably contain 1 or 2 carbon atoms and especially signify methyl, methoxy or methylthio. When a substituent is halogen, this is preferably chlorine.
R1 and R2 are each preferably hydrogen. When Rl and R2 are other than hydrogen, these are preferably in the 2- or 3-position of the benzocycloheptene residue.
When bonded to adjacent carbon atoms, R1 and R2 can form a methylenedioxy group.
When R4 is cycloalkyl, this preferably contains 5 or 6 carbon atoms. When R4 is cycloalkylalkyl, the cycloalkyl residue preferably contains from 3 to 6 carbon atoms and 1 or 2 carbon atoms in the alkylene chain. When R, is C,-. alkyl R4 can also signify benzyl or benzyl monosubstituted in the phenyl residue by chlorine, bromine, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms. When R, and R4 together with the nitrogen atom to which they are bound form a specified heterocydic ring, this is preferably a pyrrolidine or morpholine ring.
Z is preferably unsubstituted phenyl or unsubstituted 2-thienyl. When Z is substituted phenyl, RS can be alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, trifluoromethyl or halogen of atomic number from 9 to 35 and Rc can be hydrogen, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35. When bonded to adjacent carbon atoms, R and R6 together can also be methylenedioxy.
When Z is the residue III, R, can be alkyl of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35.
In one group of compounds, Z is the residue IV.
The invention also provides a process for the production of compounds of formula
I comprising
a) producing a compound of formula Ia,
wherein
R1, R2, R4 and Z are as previously defined and R3' is alkyl of 1 to 4 carbon atoms or with R4 and the nitrogen atom to which they are bound forms a pyrrolidine, piper idine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of which is substituted by alkyl of 1 to 4 carbon atoms, by reacting a compound of formula V,
wherein R1, R2, Rsl and R4 are as previously defined, with a compound of formula VI,
SMgX VI wherein
Z is as previously defined and
X is chlorine, bromine or iodine, or
b) producing a compound of formula Ib,
wherein R1, R2 and Z are as previously defined and R41 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms or cycloalkyl of 3 to 7 carbon atoms, by removing the benzyl group from a compound of formula VII,
wherein
R1, R2, R4I and Z are as previously defined.
The reaction of the aminonitrile compound of formula V with the Grignard com- pound of formula VI according to process variant a) can be effected according to known methods. For example, the reaction can be effected m a suitable solvent for
Grignard reactions, e.g. in the presence of an open chain of cyclic ether such as diethyl ether or tetrahydrofuran.
The removal cf the benzyl group from the compounds of formula VII according to process varient b) can be effected by known methods. The benzyl group is preferably removed hydrogenolytically, especially employing a palladium catalyst in a solvent which is inert under the reaction conditions, e.g. in dimethyl formamide. The hydrogenation may advantageously be effected at room temperature and at normal pressure.
The resulting compounds of formula I may be isolated and purified using conventional techniques. When required, free base forms thereof may be converted into acid addition salt forms in conventional manner and vice versa. Suitable acids for salt formation are hydrochloric, sulphuric, fumaric, maleic and naphthalene-1,5-disulphonic acid.
The starting materials of formula V can be obtained according to the following reaction scheme: A compound of formula VIII,
Wherein R, and R2 are as previously defined, is reacted with 3-oxo-glutaric acid diethyl ester to produce a compound of formula IX,
Wherein Rl and R2 are as previously defined, the compound of formula IX is reduced and decarboxylated according to known methods to yield a compound of formula X,
wherein Rl and R2 are as previously defined, and the compound of formula X
Is reacted in known manner with an alkali metal cyanide and an acid addition salt of a compound of formula XI,
wherein R,x and R4 are as previously defined, to yield a compound of formula V.
The starting materials of formula VII can be produced by reacting a compound of formula XII,
wherein R1, R2 and R41 are as previously defined, with a Grignard compound of formula VI, according to known methods, for example as for process variant a).
The compounds of formula XII can be produced from compounds of formula
VIII in manner analogous to that previously described for the preparation of compounds of formula V.
Insofar as the production of the starting materials has not been described, these are either known or may be produced in conventional manner from available materials, or by methods analogous to those described herein.
In the following Examples, all temperatures are in degrees Celsius.
EXAMPLE 1.
7-Dimethylamino-5,6,8,9-tetrahydro-7-phenyl -7H-benzocycloheptene.
A solution of 10.0 g of 7-dimethylamino-5,6,8,9-tetrahydro-7H-benzocyclohepten- 7-carbonitrile in 150 ml of anhydrous ether is added dropwise to a solution of phenyl magnesium bromide (prepared from 36.6 g of bromobenzene and 5.6 g of magnesium turnings) in 100 ml of anhydrous ether, over a period of one hour and at room tem perature. The reaction mixture is stirred for 30 minutes and thereafter 90 ml of 20% ammonium chloride solution are added dropwise with strong cooling. After separating the organic phase, the aqueous solution is shaken with ether and the combined organic solutions washed with saturated brine, dried over potassium carbonate and evaporated.
The title compound remains as an oily residue and is converted to the hydrochloride form in ethanol/acetone. M.P. 237238 (from ethanol/acetone).
The starting material can be prepared as follows:
To a solution of 14.2 g of potassium cyanide in 80 ml of ethanol and 20 ml of water are first added 17.8 g of dimethylamine hydrochloride followed by 35.0 g of 5,6,8,9-tetrahydro-7H-benzocyclohepten-7-one in 50 ml of ethanol over a period of 1.5 hours. The reaction mixture is stirred for 24 hours at room temperature, considerably reduced in volume, diluted with ice/water and made slightly alkaline by the addition of potassium hydroxide solution. The substance which precipitates is extracted with ether, the ethereal extracts washed with water, dried over potassium carbonate and reduced in volume. The residue, 7-dimethylamino-5,6,8,9-tetrahydro 7H-benzo-cyclohepten-7-carbonitrile, is recrystallized from ether/petroleum ether. M.P.
1 101 12 .
The following compounds can be produced in manner analogous to that described in Example 1, employing appropriate starting materials in approximately equivalent amounts.
R1 Ex. R1 R2 -N z M.P.
No. R2 \R4 2 H H -N e IlCi*: 208-209 3 H H -N N-Cll S Fu**: 194-195 3 4 H H -N (CH3) 2 OC1 llCl*: 214-2150 (CH CH : CHuC1 HC1*: 20S-207 7 H H - Nn 4 HC1*: 230-232 8 H H -Ng t HC1*: 23O-231 F 9 H H -N(CH3)2 eF HC1*: 241-242 CF3 10 H H $3 HC1*: 237-238 11 H H * C1 HCl*: 23to2340 12 H H -N O HC1*: 219-220
,: /3 No. R1 R2 -N Z Z M.P. No. \Rq ii 13 H 11 -N 0 v HC1*: 183-184 'U 14 H H -N(CH3)2 O CH3 HC1*: 218-220 15 li H n O SCH3 HC1*: 194-195 16 H H g 98-100 17 H H -hr I r 99-1000 CH 18 H H CH3 L/ HFu***: 12S-1260 CH(CH3)2 CH3 19 H H \ CH2 n HC1* 129-1300
* HCI = Hydrochloride
** Fu = bislfreebase] fumarate ** 1 HFu = Hydrogenfumarate EXAMPLE 20.
5,6,8,9-Tetrahydro-7-methylamino-7-phenyl-7H-benzocycloheptene.
A solution o; 25.0 g of 7 - (N - benzyl - N - methylamino) - 5,6,8,9 - tetrahydro7 - phenyl - 7H - benzocycloheptene in 500 ml of N,N-dimethyl formamide is hydrogenated in the presence of 2.5 g of 10% palladium on charcoal at normal pressure and at room temperature. After take-up of the theoretical quantity of hydrogen, the catalyst is filtered off, the filtrate evaporated to half its volume and poured onto water.
The entire mixture is shaken with ether (3 applications), the extracts washed with water, dried over magnesium sulphate and evaporated. The title compound remains as an oil and is converted to the hydrochloride form in ethanol. M.P. 275276 (after recrystallization from ethanol).
The starting material can be prepared as follows: a) The starting material is prepared as described in Example 1, using 37.5 g of
benzylmethylamine hydrochloride instead of 17.8 g of dimethylamine hydro
chloride. 7 - (N - benzyl - N - methylamino) - 5,6,8,9 - tetrahydro - 7H - benzo
cyclohepten - 7 - carbonitrile is obtained. M.P. 8990 .
b) The reaction is effected as described in Example 1, using 13.6 g of 7 - (N
benzyl - N - methylamino) - 5,6,8,9 - tetrahydro - 7H - benzocyclohepten - 7
carbonitrile instead of 10.0 g of 7 - dimethylamino - 5,6,8,9 - tetrahydro - 7H benzocyclohepten - 7 - carbonitrile. 7 - (N - benzyl - N - methylamino) - 5,6,8,9
tetrahydro - 7 - phenyl - 7H - benzocycloheptene is obtained. M.P. 129130 hydrochloride form).
The compounds of formula I exhibit pharmacological activity. In particular, the
compounds exhibit anti-depressant activity, as indicated in standard tests, for example, in the tetrabenzene antagonism test in rats.
The compounds are therefore indicated for use as anti-depressants.
For this use, an indicated daily dose is from about 0.1 to about 100 mg, con
veniently administered in divided doses 2 to 4 times a day in unit dosage form containing from about 0.025 to about 50 mg, or in sustained release form.
The compounds also exhibit psychostimulant activity, as indicated by standard tests. For example, in one standard test, the compounds are administered orally to mice and subsutaneously or intraperitoneally to rats and the effect on the excitability of both species observed over a period of several hours.
The compounds are therefore indicated for use as psycho stimulants.
Additionally, the compounds exhibit vigilance-increasing activity, as indicated in standard tests. For example, in one test, the sleep-wakefulness cycle is determined in rats in conventional manner, using an elearoencephalograph.
The compounds are therefore indicated for use as vigilance-increasing agents.
For these uses, an indicated daily dosage is from about 1 to about 500 mg, conveniently administered in divided doses 2 to 4 times a day in unit dosage form contain
ing from about 0.25 to about 250 mg of the compound admixed with a solid or liquid pharmaceutical carrier or diluent.
The compounds of formula I may be administered in pharmaceutically acceptable acid addition salt form. Such acid addition salt forms exhibit the same 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 pharmaceutically acceptable diluent pr carrier. Such compositions may be formulated in conventional manner and may be, for example, a solution or a capsule.
Suitable acids for salt formation include hydrochloric and fumaric acids.
In one group of compounds, R1, R2, R4 and Z are as previously defined. R3 is alkyl of 1 to 4 carbon atoms, or R, and R4, together with the nitrogen atom to which they are bound, form a pyrrolidine, piperidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of which is substituted by alkyl of 1 to 4 carbon atoms.
In a second group of compounds, R1 and R2 are as previously defined, R, is hydrogen, R4 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms or cycloalkyl of 3 to 7 carbon atoms and Z is a group II, III or IV as hereinbefore defined.
WHAT WE CLAIM IS:
1. A process for the production of a compound of formula I,
wherein Rl is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35,
R2 is hydrogen or, when R, is alkoxy of 1 to 4 carbon atoms, also alkoxy of 1 to 4 carbon atoms, or
R1 and R2 when bonded to adjacent carbon atoms together form a methylenedioxy group,
R, is hydrogen or alkyl of l to 4 carbon atoms,
R4 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms,
cycloalkyl of 3 to 7 carbon atoms or, when R3 is alkyl of 1 to 4 carbon atoms, may
also be benzyl or benzyl monosubstituted in the phenyl residue by chlorine, bromine,
alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms,
or
R3 and R4 together with the nitrogen atom to which they are bound form a pyrro
lidine, piporidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (29)
1. A process for the production of a compound of formula I,
wherein Rl is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35,
R2 is hydrogen or, when R, is alkoxy of 1 to 4 carbon atoms, also alkoxy of 1 to 4 carbon atoms, or
R1 and R2 when bonded to adjacent carbon atoms together form a methylenedioxy group,
R, is hydrogen or alkyl of l to 4 carbon atoms,
R4 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms,
cycloalkyl of 3 to 7 carbon atoms or, when R3 is alkyl of 1 to 4 carbon atoms, may
also be benzyl or benzyl monosubstituted in the phenyl residue by chlorine, bromine,
alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms,
or
R3 and R4 together with the nitrogen atom to which they are bound form a pyrro
lidine, piporidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of
which is substituted by alkyl of 1 to 4 carbon atoms1 and Z is
wherein,
either R is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon, alkylthio of 1 to 4 carbon atoms, trifluoromethyl or halogen of atomic number from 9 to 35 and R6 is hydrogen, alkoxy of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35, or R and RG when bonded to adjacent carbon atoms together form a methylenedioxy group,
R, is hydrogen, alkyl of 1 to 4 carbon atoms or halogen of atomic number from 9 to 35, comprising
a) producing a compound of formula Ia,
wherein
R1, R2, R4 and Z are as previously defined and R31 is alkyl of 1 to 4 carbon atoms or with R4 and the nitrogen atom to which they are bound forms a pyrrolidine, piperidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of which is substituted by alkyl of 1 to 4 carbon atoms, by reacting a compound of formula V,
wherein R1, R2, Rs! and R, are as previously defined, with a compound of formula VI, zMg-X VI
wherein Z is as previously defined
and X is chlorine, bromine or iodine, or
b) producing a compound of formula Ib,
wherein Rl, R2 and Z are as previously defined and R4' is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms or cycloalkyl of 3 to 7 carbon atoms, by removing the benzyl group from a compound of formula VII,
wherein
R1, R2, R41 and Z are as previously defined.
2. A process for production of a compound of formula I, substantially as hereinbefore described with reference to any one of the Examples.
3. A compound of formula I, whenever produced by a process as claimed in
Claim 1 or 2.
4. A compound of formula I, as defined in Claim 1.
5. A compound of Claim 4, wherein R1, R2, R4 and Z are as defined in Claim 1 and R3 is alkyl of 1 to 4 carbon atoms, or Ra and R4, together with the nitrogen atom to which they are bound, form a pyrrolidine, piperidine or morpholine ring; or a piperazine ring, the 4-nitrogen atom of which is substituted by alkyl of 1 to 4 carbon atoms.
6. A compound of Claim 4, wherein R1 and R2 are as defined in Claim 1, Era is hydrogen, R4 is alkyl of 1 to 4 carbon atoms, cycloalkylalkyl of 4 to 10 carbon atoms or cycloalkyl of 3 to 7 carbon atoms and Z is a group II, III or IV as defined in Claim 1.
7. 7 - Dimethylamino - 5,6,8,9 - tetrahydro - 7 - phenyl - 7H - benzocycloheptene.
8. A compound of Claim 4, wherein each of R1 and R2 is hydrogen, -NR3IR4 is
and Z is
9. A compound of Claim 4, wherein each of Rl and R2 is hydrogen, NR,1R is
and Z is
10. A compound of Claim 4, wherein each of Ra and Ra is hydrogen, -NR3'R4 is N(CH3)2 and Z is
11. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, -NRa'R4 is -N(CH3)2 and Z is
12. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, -NR3IR4 is -N(CH3)2 and Z is
13. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, -NR3IR4 is
and Z is
14. A compound of Claim 4, wherein each of R1 and R2 is hydrogen, NRa'R4 is
and Z is
15. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, NR3IR4 is -N(CH,)2 and Z is
16. A compound of Claim 4, wherein each of Ra and Ra is hydrogen, NR3IR4 -N(CH3)2 and Z is
17. A compound of Claim 4, wherein each of R, and Ra is hydrogen, NR3IR4 is -N(CH,)a and Z is
18. A compound of Claim 4, wherein each of R1 and R2 is hydrogen, -NR2IR4 is
and Z is
19. A compound of Claim 4, wherein each of R, and R2 is hydrogen, -NR3IR4 is
and Z is
20. A compound of Claim 4, wherein each of R, and Ra is hydrogen, -NR3IR4 is -N(CH3)2 and Z is
21. A compound of Claim 4, wherein each of R, and R2 is hydrogen, -NR3IR4 is -N(CH3)2andZis
22. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, -NR3IR4 is -N(CH3)2 and Z is
23. A compound of Claim 4, wherein each of R, and R2 is hydrogen, -NRi'R is
and Z is
24. A compound of Claim 4, wherein each of R1 and Ra is hydrogen, -NR3R4 is
and Z is
25. A compound of Claim 4, wherein each of R1 and R2 is hydrogen, -NR3'R is
and Z is
26. 5,6,8,9 - Tetrahydro - 7 - methylamino - 7 - phenyl - 7H - benzocycloheptene.
27. A compound according to any one of Claims 3 to 26 in free base form.
28. A compound according to any one of Claims 3 to 26 in acid addition salt form.
29. A pharmaceutical composition comprising a compound according to any one of Claims 3 to 26, in free base form or in pharmaceutically acceptable acid addition salt form in association with a pharmaceutically acceptable diluent or carrier.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH632177A CH628870A5 (en) | 1977-05-23 | 1977-05-23 | Process for the preparation of benzocycloheptene derivatives |
| CH632077A CH635310A5 (en) | 1977-05-23 | 1977-05-23 | Process for preparing novel benzocycloheptene derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1589776A true GB1589776A (en) | 1981-05-20 |
Family
ID=25699361
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB37900/77A Expired GB1589776A (en) | 1977-05-23 | 1977-09-12 | Tetrabenzocycloheptenes |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS53144560A (en) |
| AU (1) | AU517587B2 (en) |
| CA (1) | CA1091231A (en) |
| DE (1) | DE2740857A1 (en) |
| DK (1) | DK390477A (en) |
| ES (1) | ES462647A1 (en) |
| FI (1) | FI772729A (en) |
| FR (1) | FR2391992A1 (en) |
| GB (1) | GB1589776A (en) |
| IE (1) | IE45771B1 (en) |
| IL (1) | IL52929A (en) |
| NL (1) | NL7710247A (en) |
| NZ (1) | NZ185162A (en) |
| PH (1) | PH17683A (en) |
| PT (1) | PT67052B (en) |
| SE (1) | SE7710009L (en) |
| SU (1) | SU856378A3 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2931986B2 (en) * | 1989-02-17 | 1999-08-09 | 武田薬品工業株式会社 | Aralkylamine derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2319332A1 (en) * | 1975-07-28 | 1977-02-25 | Roussel Uclaf | NEW DERIVATIVES OF AMINOBENZOCYCLOHEPTENE AND THEIR SALTS, METHOD OF PREPARATION AND APPLICATION AS MEDICINAL PRODUCTS OF THE SAID PRODUCTS |
-
1977
- 1977-09-01 DK DK390477A patent/DK390477A/en not_active Application Discontinuation
- 1977-09-07 SE SE7710009A patent/SE7710009L/en not_active Application Discontinuation
- 1977-09-10 DE DE19772740857 patent/DE2740857A1/en not_active Withdrawn
- 1977-09-12 GB GB37900/77A patent/GB1589776A/en not_active Expired
- 1977-09-12 NZ NZ185162A patent/NZ185162A/en unknown
- 1977-09-12 IL IL52929A patent/IL52929A/en unknown
- 1977-09-12 IE IE1882/77A patent/IE45771B1/en unknown
- 1977-09-13 PH PH20223A patent/PH17683A/en unknown
- 1977-09-13 CA CA286,593A patent/CA1091231A/en not_active Expired
- 1977-09-15 AU AU28831/77A patent/AU517587B2/en not_active Expired
- 1977-09-16 FI FI772729A patent/FI772729A/en not_active Application Discontinuation
- 1977-09-19 JP JP11168177A patent/JPS53144560A/en active Pending
- 1977-09-19 NL NL7710247A patent/NL7710247A/en not_active Application Discontinuation
- 1977-09-19 FR FR7728136A patent/FR2391992A1/en active Granted
- 1977-09-19 PT PT67052A patent/PT67052B/en unknown
- 1977-09-26 ES ES462647A patent/ES462647A1/en not_active Expired
-
1979
- 1979-04-19 SU SU792754653A patent/SU856378A3/en active
Also Published As
| Publication number | Publication date |
|---|---|
| PH17683A (en) | 1984-11-02 |
| SU856378A3 (en) | 1981-08-15 |
| FR2391992B1 (en) | 1981-02-06 |
| DK390477A (en) | 1978-11-24 |
| IE45771B1 (en) | 1982-11-17 |
| DE2740857A1 (en) | 1978-12-07 |
| NL7710247A (en) | 1978-11-27 |
| IL52929A0 (en) | 1977-11-30 |
| FR2391992A1 (en) | 1978-12-22 |
| IL52929A (en) | 1981-06-29 |
| AU2883177A (en) | 1979-03-22 |
| FI772729A (en) | 1978-11-24 |
| NZ185162A (en) | 1980-03-05 |
| IE45771L (en) | 1978-11-23 |
| AU517587B2 (en) | 1981-08-13 |
| PT67052B (en) | 1979-05-14 |
| JPS53144560A (en) | 1978-12-15 |
| PT67052A (en) | 1977-10-01 |
| CA1091231A (en) | 1980-12-09 |
| ES462647A1 (en) | 1978-12-16 |
| SE7710009L (en) | 1978-11-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |