WO1997010239A1 - Acid addition salts of 2,3,4,5-tetrahydro-1h-3-benzazepine compounds - Google Patents

Acid addition salts of 2,3,4,5-tetrahydro-1h-3-benzazepine compounds Download PDF

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Publication number
WO1997010239A1
WO1997010239A1 PCT/DK1996/000383 DK9600383W WO9710239A1 WO 1997010239 A1 WO1997010239 A1 WO 1997010239A1 DK 9600383 W DK9600383 W DK 9600383W WO 9710239 A1 WO9710239 A1 WO 9710239A1
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Prior art keywords
tetrahydro
dichloro
chloro
methyl
dihydrobenzofuran
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French (fr)
Inventor
Louis Brammer Hansen
Rolf Emil Amsler
Scott Eugene Mcgraw
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Novo Nordisk AS
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Novo Nordisk AS
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Priority to EP96930028A priority Critical patent/EP0850237A1/en
Priority to BR9610162A priority patent/BR9610162A/en
Priority to JP9511574A priority patent/JPH11512403A/en
Priority to IL12360296A priority patent/IL123602A0/en
Priority to PL96325514A priority patent/PL325514A1/en
Priority to AU69235/96A priority patent/AU700596B2/en
Priority to CA002231848A priority patent/CA2231848A1/en
Publication of WO1997010239A1 publication Critical patent/WO1997010239A1/en
Priority to NO981135A priority patent/NO981135L/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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

Definitions

  • the present invention relates to crystalline salts of (S) ( + )-8-chloro-5- (5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepine-7-ol, their preparation and use as therapeutic agents.
  • the compound of formula I is used as a therapeutic agent in the form of an acid addition salt. Further, it has been found that some acid addition salts of the compound of formula I do form alternate polymorphic forms. This is pharmaceuti ⁇ cally undesirable because of the potential that the salt occurs in more than one crystalline form making it very difficult to predict how the various parts of the body will react to the different crystalline forms.
  • the present invention provides a series of crystalline salts of
  • Preferred salts of the invention are (S) ( + )-8-chloro-5-(5,6-dichloro-2,3- dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7- ol, hemifumarate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofu- ran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7-ol, L( + )-hemi- tartrate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2, 3, 4,5-tetrahydro-1 H-3-benzazepin-7-ol, maleate; (S) ( + )-8- chloro-5-(5, 6-dichloro-2,3-di
  • the acid addition salts of the (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihy- drobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepi ⁇ e-7-ol are prepared by dissolving the acid of the corresponding addition salt and the compound of formula I in a common solvent, and crystallizing the resulting salt from the solution.
  • Examples of the common solvents include lower aliphalic alcohols such as ethanol, methanol, 2-propanol, 2-butanol, 1 -hexanol and solvents like isobutylmethylketone and tetrahydrofuran.
  • lower aliphalic alcohols such as ethanol, methanol, 2-propanol, 2-butanol, 1 -hexanol and solvents like isobutylmethylketone and tetrahydrofuran.
  • the present invention also provides pharmaceutical compositions com ⁇ prising crystalline salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydro- benzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol and a pharmaceutically acceptable carrier.
  • compositions of this invention are usually adapted for oral admini ⁇ stration, but formulations for dissolution for parenteral administration are also within the scope of this invention.
  • composition is usually presented as a unit dose composition contain ⁇ ing 0.01 mg - 1000 mg for oral dosing.
  • Typical dosage for antiphsy- chotic effect would vary between 0.1 - 400 mg, preferably between 1 .0 - 200 mg per day divided in 2 or 3 doses when administered orally.
  • Preferred unit dosage forms include in solid form, tablets or capsules, in liquid form, solutions, suspensions, emulsions, elixirs or capsules filled with the same, or in form of sterile injectable solutions.
  • composition of this invention may be formulated by conventional methods of galenic pharmacy.
  • Conventional excipients are such pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral or oral application which do not deleteriously react with the active compound.
  • examples of such carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, syrup, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, agar, pectin, acacia, amylose, magnesium stearate, talc, silicic acid, stearic acid, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, hydroxymethylcellulose and polyvinylpyrrolidone.
  • the pharmaceutical preparations can be sterilized and mixed, if desired, with auxiliary agents, such as binders, lubricants, preservatives, dis- integrants, stabilizers, wetting agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or colouring substances and the like, which do not deleteriously react with the active compound.
  • auxiliary agents such as binders, lubricants, preservatives, dis- integrants, stabilizers, wetting agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or colouring substances and the like, which do not deleteriously react with the active compound.
  • injectable solutions or suspensions preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
  • tablets, dragees, or cap ⁇ sules having talc and/or a carbohydrate carrier or binder or the like, the carrier preferably being lactose and/or corn starch and/or potato starch.
  • a syrup, elixir or like can be used when a sweetened vehicle can be employed.
  • a typical tablet which may be prepared by conventional tabletting tech- niques, contains:
  • the invention also provides methods of treatment of certain disorders in the central nerveous system related to dysfunctions of the dopamine D-1 receptor system, e.g. psychosis, depression, pain and Parkinson's disease in mammals including humans which methods comprises admini- stering an effective amount of a pharmaceutically acceptable crystalline salt of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepine-7-ol.
  • the invention further provides pharmaceutically acceptable crystalline salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol for use in the treatment of disorders in the central nerveous system related to dysfunctions of the dopamine D-1 receptor system, e.g. psychosis, depression, pain and Parkinson's disease.
  • the preparation was carried out analogously to the preparation in Example 1 using L( + )-tartaric acid and 20 mmol of the compound of for ⁇ mula I .

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  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pain & Pain Management (AREA)
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Abstract

The invention provides a series of crystalline salts of (S) (+)-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7-ol, their preparation and use as therapeutic agents.

Description

Acid Addition Salts of 2,3,4,5-tetrahydro-1 H-3-benzazepine Compounds
The present invention relates to crystalline salts of (S) ( + )-8-chloro-5- (5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepine-7-ol, their preparation and use as therapeutic agents.
International patent appl. No. WO 93/17012 discloses a class of com¬ pounds exhibiting strong antidopaminergic effects and thus making them useful in treatment of disorders in the central nervous system related to dysfunctions of the dopamine D-1 receptor system, e.g. psychosis, pain, depression and Parkinson's disease.
In example 3 of International appl. No. WO 93/17012 the preparation of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol of formula I:
Figure imgf000003_0001
is described.
Because of its poor solubility, it is preferred that the compound of formula I is used as a therapeutic agent in the form of an acid addition salt. Further, it has been found that some acid addition salts of the compound of formula I do form alternate polymorphic forms. This is pharmaceuti¬ cally undesirable because of the potential that the salt occurs in more than one crystalline form making it very difficult to predict how the various parts of the body will react to the different crystalline forms.
In general, for commercial use it is important to have a physiologically acceptable salt with good bioavailability, good handling properties, and reproducible crystalline form.
Surprisingly, it has now been found that a series of new pharmaceuti¬ cally acceptable acid addition salts of the compound of formula I can be obtained in a reproducible crystalline form.
Accordingly, the present invention provides a series of crystalline salts of
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol derived from organic acids such as fumaric, tartaric, maleic and mandelic acids.
Preferred salts of the invention are (S) ( + )-8-chloro-5-(5,6-dichloro-2,3- dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7- ol, hemifumarate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofu- ran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7-ol, L( + )-hemi- tartrate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2, 3, 4,5-tetrahydro-1 H-3-benzazepin-7-ol, maleate; (S) ( + )-8- chloro-5-(5, 6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-2, 3,4,5- tetrahydro-1 H-3-benzazepin-7-ol, L( + (-mandelate.
The acid addition salts of the (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihy- drobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepiπe-7-ol are prepared by dissolving the acid of the corresponding addition salt and the compound of formula I in a common solvent, and crystallizing the resulting salt from the solution.
Examples of the common solvents include lower aliphalic alcohols such as ethanol, methanol, 2-propanol, 2-butanol, 1 -hexanol and solvents like isobutylmethylketone and tetrahydrofuran.
The present invention also provides pharmaceutical compositions com¬ prising crystalline salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydro- benzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol and a pharmaceutically acceptable carrier.
The compositions of this invention are usually adapted for oral admini¬ stration, but formulations for dissolution for parenteral administration are also within the scope of this invention.
The composition is usually presented as a unit dose composition contain¬ ing 0.01 mg - 1000 mg for oral dosing. Typical dosage for antiphsy- chotic effect would vary between 0.1 - 400 mg, preferably between 1 .0 - 200 mg per day divided in 2 or 3 doses when administered orally.
Preferred unit dosage forms include in solid form, tablets or capsules, in liquid form, solutions, suspensions, emulsions, elixirs or capsules filled with the same, or in form of sterile injectable solutions.
The composition of this invention may be formulated by conventional methods of galenic pharmacy.
Conventional excipients are such pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral or oral application which do not deleteriously react with the active compound. Examples of such carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, syrup, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, agar, pectin, acacia, amylose, magnesium stearate, talc, silicic acid, stearic acid, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, hydroxymethylcellulose and polyvinylpyrrolidone.
The pharmaceutical preparations can be sterilized and mixed, if desired, with auxiliary agents, such as binders, lubricants, preservatives, dis- integrants, stabilizers, wetting agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or colouring substances and the like, which do not deleteriously react with the active compound.
For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
For oral administration, particularly suitable are tablets, dragees, or cap¬ sules having talc and/or a carbohydrate carrier or binder or the like, the carrier preferably being lactose and/or corn starch and/or potato starch. A syrup, elixir or like can be used when a sweetened vehicle can be employed.
A typical tablet, which may be prepared by conventional tabletting tech- niques, contains:
Active compound 10 mg
Lactosum 67.8 mg Ph. Eur.
Avicel® 31 .4 mg Amberlite® IRP 88 1 .0 mg
Magnesii stearas 0.25 mg Ph. Eur. The invention also provides methods of treatment of certain disorders in the central nerveous system related to dysfunctions of the dopamine D-1 receptor system, e.g. psychosis, depression, pain and Parkinson's disease in mammals including humans which methods comprises admini- stering an effective amount of a pharmaceutically acceptable crystalline salt of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2,3,4,5-tetrahydro- 1 H-3-benzazepine-7-ol.
The invention further provides pharmaceutically acceptable crystalline salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3- methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol for use in the treatment of disorders in the central nerveous system related to dysfunctions of the dopamine D-1 receptor system, e.g. psychosis, depression, pain and Parkinson's disease.
The acid addition salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydro- benzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol of the invention were synthesized and crystallized from common solvents as described in the following examples.
EXAMPLE 1
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4,5-tetrahydro-1 H-3-benzazepin-7-ol, hemifumarate
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4,5-tetrahydro-1 H-3-benzazepin-7-ol (7.97 g, 20 mmol) was dis¬ solved 99% ethanol at 70° C. Fumaric acid (2.32 g, 20 mmol) was added. The solution was cooled to 0°C, and the resulting suspension was filtered. The filtercake was washed with 99% ethanol (3 x 20 ml] and dried to constant weight. Yield : 8.80 g (96%) of white crystalline product. M.p. by DSC: 298 °C.
Elemental Analysis:
Figure imgf000008_0001
456.8 g/mol) Calculated: C 55.22 H 4.41 N 3.07 % Found: C 55.30 H 4.55 N 3.94 %
Alternate polymorphic forms: None
EXAMPLE 2
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-
2,3,4, 5-tetrahydro-1 H-3-benzazepin-7-ol, L( + )-hemιtartrate
The preparation was carried out analogously to the preparation in Example 1 using L( + )-tartaric acid and 20 mmol of the compound of for¬ mula I .
Yield: 7.75 g (82%) of white crystalline product. M.p. by DSC: 276°C.
Elemental Analysis: (C21H21CI3N1O5, 473.8 g/mol):
Calculated: C 53.24 H 4.47 N 2.96 %
Found: C 53.21 H 4.55 N 2.80 %
Alternate polymorphic form: None
EXAMPLE 3
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4, 5-tetrahydro-1 H-3-benzazepin-7-ol, maleate
The preparation of the compound was carried out analogously to the preparation in Example 1 using maleic acid, and 20 mmol of the com¬ pound of formula I. Yield: 7.61 g (74%) of white crystalline product. M.p. by DSC: 234°C.
Elemental Analysis: (C23H22CI3N.,O8, 514.8 g/mol) : Calculated: C 53.66 H 4.31 N 2.72 % Found: C 53.79 H 4.37 N 2.56 %
Alternate polymorphic form: None
EXAMPLE 4
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-
2,3,4, 5-tetrahydro- 1 H-3-benzazepin-7-ol, L( + )-mandelate
The preparation of the compound was carried out analogously to the preparation in Example 1 using L( + )-mandelic acid, and 20 mmol of the compound of formula I.
Yield: 10.35 g (94%) of white crystalline product. M.p. by DSC: 249°C.
Elemental analysis: (C27H2θCI3N1O5, 550.9 g/mol):
Calculated: C 58.87 H 4.76 N 2.54 %
Found: C 58.97 H 4.88 N 2.50 %
Alternate polymorphic form: None

Claims

1_ Crystalline salts of (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydro- benzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7-ol, derived from fumaric acid, L( + )-tartaric acid, maleic acid and L( + )- mandelic acid.
2, A crystalline salt according to claim 1 which is (S) ( + )-8-chloro-
5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl-2,3,4, 5-tetrahydro- 1 H-3-beπzazepin-7-ol, hemifumarate; (S) ( + )-8-chloro-5-(5,6-dichloro-
2,3-dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-ben- zazepin-7-ol, L( + )-hemitartrate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3- dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7- ol, maleate; (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)- 3-methyl-2,3,4,5-tetrahydro-1 H-3-benzazepin-7-ol, L( + )-mandelate.
The use of a crystalline salt according to claims 1 or 2 as a medicament.
4,. The use of a salt according to claims 1 or 2 for the preparation of a pharmaceutical composition for treating an indication related to dysfunctions of the dopamine D-1 receptor system.
JL A pharmaceutical composition comprising a crystalline salt according to claim 1 or 2 together with a pharmaceutically acceptable carrier or diluent.
A pharmaceutical composition for use in treating an indication related to dysfunctions of the dopamine D-1 receptor system comprising an effective amount of a crystalline salt according to claim 1 or 2, together with a pharmaceutically acceptable carrier or diluent. 1__ The pharmaceutical composition according to claim 5 or 6 in the form of an oral dosage unit containing from 0.1 -400 mg of the active ingredients.
__. A process for the preparation of crystalline acid addition salts of
(S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4, 5-tetrahydro-1 H-3-benzazepine-7-ol according to claims 1 or 2, which process comprises dissolving the acid of the corresponding addition salt and (S) ( + )-8-chloro-5-(5,6-dichloro-2,3-dihydrobenzofuran- 7-yl)-3-methyl-2,3,4, 5-tetrahydro-1 H-3-benzazepine-7-ol in a common solvent, and crystallising the resulting salt from the solution.
∑L A method of treating an indication related to dysfunctions of the dopamine D-1 receptor system in a mammal comprising administering an effective amount of a crystalline salt according to claim 1 or 2.
10. A method according to claim 9 wherein the indication is related to psycosis.
1 1 . A method of treating an indication related to dysfunctions of the dopamine D-1 receptor system in a mammal comprising administering a pharmaceutical composition according to claim 5.
1 2. A process for the manufacture of a pharmaceutical composition to be used in the treatment of an indication related to dysfunctions of the dopamine D-1 receptor system, which process comprises bringing a crystalline salt according to claim 1 or 2 into a galenical dosage form.
PCT/DK1996/000383 1995-09-15 1996-09-12 Acid addition salts of 2,3,4,5-tetrahydro-1h-3-benzazepine compounds Ceased WO1997010239A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP96930028A EP0850237A1 (en) 1995-09-15 1996-09-12 Acid addition salts of 2,3,4,5-tetrahydro-1h-3-benzazepine compounds
BR9610162A BR9610162A (en) 1995-09-15 1996-09-12 Compounds use a crystalline salt pharmaceutical composition processes for the preparation of acid addition salts of a compound for the treatment of an indication related to dysfunctions of the D-1 dopamine receptor system in a mammal and for the manufacture of a pharmaceutical composition
JP9511574A JPH11512403A (en) 1995-09-15 1996-09-12 Acid addition salt of 2,3,4,5-tetrahydro-1H-3-benzazepine compound
IL12360296A IL123602A0 (en) 1995-09-15 1996-09-12 Salts of 2,3,4,5-Tetrahydro-1H-3-Benzazepine compounds
PL96325514A PL325514A1 (en) 1995-09-15 1996-09-12 Addition salts formed with acids of 2,3,4,5-tetrahydro-1h-3-benzazepinic compounds
AU69235/96A AU700596B2 (en) 1995-09-15 1996-09-12 Acid addition salts of 2,3,4,5-tetrahydro-1H-3-benzazepine compounds
CA002231848A CA2231848A1 (en) 1995-09-15 1996-09-12 Acid addition salts of 2,3,4,5-tetrahydro-1h-3-benzazepine compounds
NO981135A NO981135L (en) 1995-09-15 1998-03-13 Acid addition salts of 2,3,4,5-tetrahydro-1H-3-benzazepine compounds

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DK103095 1995-09-15

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AU (1) AU700596B2 (en)
BR (1) BR9610162A (en)
CA (1) CA2231848A1 (en)
CZ (1) CZ77898A3 (en)
HU (1) HUP9900746A3 (en)
IL (1) IL123602A0 (en)
NO (1) NO981135L (en)
PL (1) PL325514A1 (en)
WO (1) WO1997010239A1 (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993017012A1 (en) * 1992-02-24 1993-09-02 Novo Nordisk A/S 2,3,4,5-tetrahydro-1h-3-benzazepines and pharmaceutically acceptable acid addition salts thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
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CN1200121A (en) 1998-11-25
EP0850237A1 (en) 1998-07-01
MX9802000A (en) 1998-08-30
NO981135L (en) 1998-03-13
JPH11512403A (en) 1999-10-26
HUP9900746A2 (en) 1999-09-28
HUP9900746A3 (en) 1999-11-29
CA2231848A1 (en) 1997-03-20
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AU6923596A (en) 1997-04-01
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