DE3407654C2 - Use of benzamide derivatives - Google Patents
Use of benzamide derivativesInfo
- Publication number
- DE3407654C2 DE3407654C2 DE3407654A DE3407654A DE3407654C2 DE 3407654 C2 DE3407654 C2 DE 3407654C2 DE 3407654 A DE3407654 A DE 3407654A DE 3407654 A DE3407654 A DE 3407654A DE 3407654 C2 DE3407654 C2 DE 3407654C2
- Authority
- DE
- Germany
- Prior art keywords
- aminoethyl
- compounds
- addition salts
- acid addition
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/77—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
-
- 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
-
- 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
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Die vorliegende Erfindung betrifft die Verwendung von Benzamid- Derivaten der allgemeinen FormelThe present invention relates to the use of benzamide Derivatives of the general formula
worin R¹ und R² unabhängig voneinander Wasserstoff, Halogen, nieder Alkyl, nieder Alkoxy, Cyano, Trifluormethyl, Sulfamoyl, Mono-niederalkylsulfamoyl oder Di-niederalkylsulfamoyl oder, wenn sie benachbart sind, zusammen eine Methylendioxy-Gruppe bedeuten, mit der Maßgabe, daß, falls R¹ Brom in 3-Stellung bedeutet, R² von Wasserstoff verschieden ist, sowie pharmazeutisch verwendbare Säureadditionssalze davon, zur Bekämpfung von depressiven Zuständen insbes. der Parkinsonschen Erkrankung.wherein R¹ and R² are independently hydrogen, Halogen, lower alkyl, lower alkoxy, cyano, Trifluoromethyl, sulfamoyl, mono-lower alkyl sulfamoyl or di-lower alkyl sulfamoyl or, if adjacent together are a methylenedioxy group mean, with the proviso that if R¹ bromine in 3-position means R² is different from hydrogen, as well as pharmaceutically usable acid addition salts thereof, to combat depressive conditions, especially the Parkinson's disease.
Diese Verbindungen sind teilweise bereits aus beispielsweise der deutschen Offenlegungsschrift 24 58 908 bekannt, doch wurde überraschenderweise gefunden, daß sie bei geringer Toxizität interessante und therapeutisch verwertbare pharmakodynamische Eigenschaften aufweisen. In Tierversuchen konnte nämlich gezeigt werden, daß die Verbindungen der obigen Formel I sowie ihre pharmazeutisch verwendbaren Säureadditionssalze Monoaminooxidase (MAO) hemmende Eigenschaften besitzen und daher bei der Bekämpfung von depressiven Zuständen insbes. Parkinsonismus Verwendung finden können.Some of these connections are already made, for example known from German Offenlegungsschrift 24 58 908, yet it was surprisingly found that she interesting and therapeutically usable with low toxicity have pharmacodynamic properties. In Animal experiments have shown that the compounds of Formula I above and their pharmaceutically usable acid addition salts Monoamine oxidase (MAO) have inhibitory properties and therefore especially in the fight against depressive states. Parkinsonism can be used.
Die DE 32 00 258 A1 offenbart substituierte 1-Benzoyl-2- phenylimino-imidazolidine, die eine analgetische Wirkung besitzen sollen. Die DE-A 32 62 568 offenbart Alkanolaminderivate, die eine kardioselektive β-andrenergetische Blockierungsaktivität besitzen sollen.DE 32 00 258 A1 discloses substituted 1-benzoyl-2- phenylimino-imidazolidines, which have an analgesic effect should. DE-A 32 62 568 discloses alkanolamine derivatives, which has cardioselective β-andrenergic blocking activity should own.
In der DE 26 16 486 A1 sowie in J. Org. Chem. Bd. 6, Seiten 895-901 (1941) und in J. Am. Chem. Soc. Bd 61, Seiten 822-825 (1939) werden den erfindungsgemäß zu verwendenden Benz amid-Derivaten ähnliche Verbindungen offenbart, ohne daß eine medizinische Verwendbarkeit dieser Verbindungen offenbart oder nahegelegt wird.In DE 26 16 486 A1 and in J. Org. Chem. Vol. 6, pages 895-901 (1941) and in J. Am. Chem. Soc. Vol 61, pages 822-825 (1939) describe the benz to be used according to the invention compounds similar to amide derivatives are disclosed without a medical utility of these compounds disclosed or is suggested.
Für die strukturell andersartigen Verbindungen der DE 26 13 420 A1 wird eine antipsychotische Aktivität geltend gemacht.For the structurally different connections of DE 26 13 420 A1 an antipsychotic activity is claimed.
L. Anker et al., Helv. Chim. Acta 66, 2 (1983), 524-556 beschreibt Untersuchungen an N-Aminoalkylbenzamiden und N-Aminoalkyl-o- methoxybenzamiden hinsichtlich ihrer Eignung als Dopamin- Antagoniten.L. Anker et al., Helv. Chim. Acta 66, 2 (1983), 524-556 Investigations on N-aminoalkylbenzamides and N-aminoalkyl-o- methoxybenzamides with regard to their suitability as dopamine Antagonites.
Aus diesem Stand der Technik ergibt sich jedoch nicht, daß die erfindungsgemäß zu verwendenden Benzamid-Derivate zur Bekämpfung von depressiven Zuständen, insbes. der Parkinsonschen Erkrankung vorteilhaft geeignet sein könnten. However, it does not follow from this prior art that the benzamide derivatives to be used according to the invention Combating depressive states, especially the Parkinson's disease could be beneficial.
Der in dieser Beschreibung verwendete Ausdruck "nieder Alkyl" bezieht sich auf geradkettige und verzweigte Kohlenwasserstoffreste mit 1-6, vorzugsweise 1-4 Kohlenstoffatomen, wie Methyl, Äthyl, n-Propyl, Isopropyl, N-Butyl, Isobutyl, tert. Butyl und dergleichen. Der Ausdruck "nieder Alkoxy" bezieht sich auf niedere Alkyläthergruppen, in denen der Ausdruck "nieder Alkyl" die obige Bedeutung besitzt. Der Ausdruck "Halogen" umfaßt die vier Halogene Fluor, Chlor, Brom und Jod. Der Ausdruck "Abgangsgruppe" bedeutet im Rahmen der vorliegenden Erfindung bekannte Gruppen, wie Halogen, vorzugsweise Chlor oder Brom, Arylsulfonyloxy, wie etwa Tosyloxy, Alkylsulfonyloxy, wie etwa Mesyloxy, und dergleichen.The term "down" used in this description Alkyl "refers to straight chain and branched hydrocarbon residues with 1-6, preferably 1-4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, N-butyl, Isobutyl, tert. Butyl and the like. The expression "down Alkoxy "refers to lower alkyl ether groups, in which the expression "lower alkyl" has the above meaning. The term "halogen" includes the four halogens Fluorine, chlorine, bromine and iodine. The term "leaving group" means known within the scope of the present invention Groups such as halogen, preferably chlorine or bromine, arylsulfonyloxy, such as tosyloxy, alkylsulfonyloxy such as Mesyloxy, and the like.
Der Ausdruck "pharmazeutisch verwendbare Säureadditionssalze" umfaßt Salze mit anorganischen und organischen Säuren, wie Salzsäure, Bromwasserstoffsäure, Salpetersäure, Schwefelsäure, Phosphorsäure, Citronensäure, Ameisensäure, Maleinsäure, Essigsäure, Bernsteinsäure, Weinsäure, Methansulfonsäure, p-Toluolsulfonsäure und dergleichen. Solche Salze können im Hinblick auf den Stand der Technik und unter Berücksichtigung der Natur der in ein Salz zu überführenden Verbindung durch jeden Fachmann ohne weiteres hergestellt werden.The term "pharmaceutically acceptable acid addition salts" includes salts with inorganic and organic Acids, such as hydrochloric acid, hydrobromic acid, nitric acid, Sulfuric acid, phosphoric acid, citric acid, Formic acid, maleic acid, acetic acid, succinic acid, Tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and the like. Such salts can be considered with regard to the state the technology and taking into account the nature of the in a Salt to be transferred by any specialist can be easily produced.
Bevorzugte Verbindungen der Formel I sind solche, worin R¹ und R² unabhängig voneinander je Wasserstoff, Halogen, nieder Alkyl, nieder Alkoxy, Cyano oder Trifluormethyl bedeuten.Preferred compounds of formula I are those where R¹ and R² are each independently hydrogen, Halogen, lower alkyl, lower alkoxy, cyano or trifluoromethyl mean.
Besonders bevorzugt sind solche Verbindungen der Formel I, worin R¹ und R² unabhängig voneinander je Wasserstoff, Halogen oder nieder Alkyl bedeuten.Such compounds are particularly preferred Formula I, in which R¹ and R² are each independently hydrogen, Halogen or lower alkyl.
Sind die Verbindungen der Formel I disubstituiert, so befinden sich die Substituenten vorzugsweise in 2,3-, 2,4-, 2,5-, 3,4- oder 3,6-Stellung, besonders bevorzugt in 2,4- oder 3,4-Stellung. If the compounds of the formula I are disubstituted, so are the substituents are preferably in 2,3-, 2,4-, 2,5-, 3,4- or 3,6-position, particularly preferred in 2,4- or 3,4-position.
Ganz besonders bevorzugte Verbindungen der Formel I sind:Very particularly preferred compounds of the formula I. are:
N-(2-Aminoäthyl)-p-chlorbenzamid,
N-(2-Aminoäthyl)-p-fluorbenzamid,
N-(2-Aminoäthyl)-p-brombenzamid,
N-(2-Aminoäthyl)-3,4-dichlorbenzamid,
N-(2-Aminoäthyl)-2,4-dichlorbenzamid und
N-(2-Aminoäthyl)benzamid.N- (2-aminoethyl) -p-chlorobenzamide,
N- (2-aminoethyl) -p-fluorobenzamide,
N- (2-aminoethyl) -p-bromobenzamide,
N- (2-aminoethyl) -3,4-dichlorobenzamide,
N- (2-aminoethyl) -2,4-dichlorobenzamide and
N- (2-aminoethyl) benzamide.
Die Verbindungen der Formel I und deren pharmazeutisch verwendbare Säureadditionssalze können in bekannter oder an sich bekannter Weise hergestellt werden.The compounds of formula I and their pharmaceutical usable acid addition salts can in known or be produced in a manner known per se.
Die Monoaminoxidase-(MAO) hemmende Aktivität der erfindungsgemäß eingesetzten Verbindungen kann unter Verwendung von Standardmethoden bestimmt werden. So wurden die zu prüfenden Präparate p. o. an Ratten verabreicht. Zwei Stunden danach wurden die Tiere getötet und die MAO hemmende Aktivität in Homogenaten des Gehirns und der Leber nach der in Biochem. Pharmacol. 12 (1963) 1439-1441 beschriebenen Methode, jedoch unter Verwendung von Phenäthylamin (2 · 10-5 Mol · 1-1) anstelle von Tyramin als Substrat, gemessen. Die so ermittelte Aktivität einiger erfindungsgemäßer Verbindungen sowie deren Toxizität wird aus den folgenden ED₅₀-Werten (µmol/kg, p. o. an der Ratte) bzw. LD₅₀-Werten (mg/kg, p. o. an der Maus) ersichtlich:The monoamine oxidase (MAO) inhibitory activity of the compounds used according to the invention can be determined using standard methods. The preparations to be tested were administered po to rats. The animals were sacrificed two hours later and the MAO inhibitory activity in homogenates of the brain and liver after that in Biochem. Pharmacol. 12 (1963) 1439-1441, but using phenethylamine (2 · 10 -5 mol · 1 -1 ) instead of tyramine as the substrate. The activity of some compounds according to the invention determined in this way and their toxicity can be seen from the following ED folgenden values (µmol / kg, po on the rat) or LD₅₀ values (mg / kg, po on the mouse):
Die Verbindung der Formel I sowie deren pharmazeutisch verwendbaren Säureadditionssalze können als Heilmittel, z. B. in Form pharmazeutischer Präparate, Verwendung finden. Die pharmazeutischen Präparate können oral, z. B. in Form von Tabletten, Lacktabletten, Drag´es, Hart- und Weichgelatinekapseln, Lösungen, Emulsionen oder Suspensionen, verabreicht werden. Die Verabreichung kann aber auch rektal, z. B. in Form von Suppositorien, oder parenteral, z. B. in Form von Injektionslösungen, erfolgen.The compound of formula I and its pharmaceutical usable acid addition salts can be used as remedies, e.g. B. in the form of pharmaceutical preparations, use Find. The pharmaceutical preparations can oral, e.g. B. in the form of tablets, coated tablets, drages, Hard and soft gelatin capsules, solutions, emulsions or Suspensions. The administration can but also rectally, e.g. B. in the form of suppositories, or parenterally, e.g. B. in the form of injection solutions.
Zur Herstellung von Tabletten, Lacktabletten, Drag´es und Hartgelatinekapseln können die Verbindungen der Formel I und deren pharmazeutisch verwendbare Säureadditionssalze mit pharmazeutisch inerten, anorganischen oder organischen Excipientien verarbeitet werden. Als solche Excipientien kann man z. B. für Tabletten, Drag´es und Hartgelatinekapseln Lactose, Maisstärke oder Derivate davon, Talk, Stearinsäure oder deren Salze etc. verwenden.For the production of tablets, coated tablets, drag'es and hard gelatin capsules can contain the compounds of the formula I. and their pharmaceutically acceptable acid addition salts with pharmaceutically inert, inorganic or organic Excipients are processed. As such excipients can you e.g. B. for tablets, drages and hard gelatin capsules Lactose, corn starch or derivatives thereof, talc, stearic acid or use their salts etc.
Für Weichgelatinekapseln eignen sich als Excipientien z. B. vegetabile Öle, Wachse, Fette, halbfeste und flüssige Polyole etc.Excipients are suitable for soft gelatin capsules e.g. B. vegetable oils, waxes, fats, semi-solid and liquid Polyols etc.
Zur Herstellung von Lösungen und Sirupen eignen sich als Excipientien z. B. Wasser, Polyole, Saccharose, Invertzucker, Glukose etc.Suitable for the production of solutions and syrups as excipients e.g. B. water, polyols, sucrose, invert sugar, Glucose etc.
Für Injektionslösungen eignen sich als Excipientien z. B. Wasser, Alkohole, Polyole, Glycerin, vegetabile Öle etc.Excipients are suitable for injection solutions e.g. B. water, alcohols, polyols, glycerin, vegetable oils Etc.
Für Suppositorien eignen sich als Excipientien z. B. natürliche oder gehärtete Öle, Wachse, Fette, halbflüssige oder flüssige Polyole etc.For suppositories are suitable as excipients such. B. natural or hardened oils, waxes, fats, semi-liquid or liquid polyols etc.
Die pharmazeutischen Präparate können daneben noch Konservierungsmittel, Lösungsvermittler, Stabilisierungsmittel, Netzmittel, Emulgiermittel, Süßmittel, Färbemittel, Aromatisierungsmittel, Salze zur Veränderung des osmotischen Druckes, Puffer, Überzugsmittel oder Antioxidantien enthalten. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.The pharmaceutical preparations can also Preservatives, solubilizers, stabilizers, Wetting agents, emulsifiers, sweeteners, colorants, Flavoring agents, salts for changing the osmotic pressure, buffers, coating agents or antioxidants contain. You can also use others therapeutically contain valuable substances.
Erfindungsgemäß kann man Verbindungen der allgemeinen Formel I sowie deren pharmazeutisch verwendbare Säureadditionssalze bei der Bekämpfung von depressiven Zuständen insbes. Parkinsonismus verwenden. Die Dosierung kann innerhalb weiter Grenzen variieren und ist natürlich in jedem einzelnen Fall den individuellen Gegebenheiten anzupassen. Im allgemeinen dürfte bei oraler Verabreichung eine Tagesdosis von etwa 10 bis 100 mg einer Verbindung der allgemeinen Formel I angemessen sein, wobei aber die soeben angegebene obere Grenze auch überschritten werden kann, wenn sich dies als angezeigt erweisen sollte. According to the invention, compounds of the general Formula I and their pharmaceutically usable Acid addition salts in the fight against use depressive conditions, especially Parkinsonism. The dosage can vary and is within wide limits of course in each individual case the individual circumstances adapt. In general, with oral Administration of a daily dose of about 10 to 100 mg Compound of general formula I may be appropriate, wherein but also exceeded the upper limit just specified if this turns out to be appropriate.
Die folgenden Herstellungsbeispiele sollen die vorliegende Erfindung erläutern, sie jedoch in keiner Weise einschränken. Alle Temperaturen sind in Celsius-Graden angegeben.The following manufacturing examples are intended to illustrate the present invention explain, but do not limit them in any way. All temperatures are given in degrees Celsius.
1-5 werden gemischt und durch ein Sieb mit 0,5 mm Maschenweite gesiebt. Danach wird 6 zugefügt und gemischt. Diese abfüllfertige Mischung wird in Gelatinesteckkapseln geeigneter Größe (z. B. Nr. 2) mit einem Einzelfüllgewicht von 240 mg abgefüllt. 1-5 are mixed and passed through a 0.5 mm sieve Sieve mesh size. Then 6 is added and mixed. This ready-to-fill mixture is packaged in gelatin capsules suitable size (e.g. No. 2) with a single filling weight of 240 mg.
1-3 werden gemischt und durch ein Sieb mit 0,5 mm Maschenweite gesiebt. Diese Pulvermischung wird mit einer alkoholischen Lösung von 4 befeuchtet und geknetet. Die feuchte Masse wird granuliert, getrocknet und auf eine geeignete Korngröße zugerüstet. Dem getrockneten Granulat werden nacheinander 5, 6 und 7 zugeführt und gemischt. Die preßfertige Mischung wird zu Tabletten geeigneter Größe mit einem Sollgewicht von 200 mg verpreßt. 1-3 are mixed and passed through a 0.5 mm sieve Sieve mesh size. This powder mixture is made with a alcoholic solution of 4 moistened and kneaded. The moist mass is granulated, dried and placed on a suitable grain size prepared. The dried granules 5, 6 and 7 are fed in succession and mixed. The ready-to-press mixture becomes tablets of a suitable size pressed with a target weight of 200 mg.
1-5 werden gemischt und durch ein Sieb mit 0,5 mm Maschenweite gesiebt. Danach wird 6 zugefügt und gemischt. Diese abfüllfertige Mischung wird in Gelatinesteckkapseln geeigneter Größe (z. B. Nr. 2) mit einem Einzelfüllgewicht von 240 mg abgefüllt. 1-5 are mixed and passed through a 0.5 mm sieve Sieve mesh size. Then 6 is added and mixed. This ready-to-fill mixture is packaged in gelatin capsules suitable size (e.g. No. 2) with a single filling weight of 240 mg.
1-3 werden gemischt und durch ein Sieb mit 0,5 mm Maschenweite gesiebt. Diese Pulvermischung wird mit einer alkoholischen Lösung von 4 befeuchtet und geknetet. Die feuchte Masse wird granuliert, getrocknet und auf eine geeignete Korngröße zugerüstet. Dem getrockneten Granulat werden nacheinander 5, 6 und 7 zugeführt und gemischt. Die preßfertige Mischung wird zu Tabletten geeigneter Größe mit einem Sollgewicht von 200 mg verpreßt.1-3 are mixed and passed through a 0.5 mm sieve Sieve mesh size. This powder mixture is made with a alcoholic solution of 4 moistened and kneaded. The moist mass is granulated, dried and placed on a suitable grain size prepared. The dried granules 5, 6 and 7 are fed in succession and mixed. The ready-to-press mixture becomes tablets of a suitable size pressed with a target weight of 200 mg.
Claims (3)
- N-(2-Aminoäthyl)-p-chlorbenzamid,
- N-(2-Aminoäthyl)-p-fluorbenzamid,
- N-(2-Aminoäthyl)-p-brombenzamid,
- N-(2-Aminoäthyl)-3,4-dichlorbenzamid,
- N-(2-Aminoäthyl)-2,4-dichlorbenzamid oder
- N-(2-Aminoäthyl)benzamid,
oder pharmazeutisch verwendbaren Säureadditionssalze davon.3. Use according to claim 1 of the compounds
- N- (2-aminoethyl) -p-chlorobenzamide,
- N- (2-aminoethyl) -p-fluorobenzamide,
- N- (2-aminoethyl) -p-bromobenzamide,
- N- (2-aminoethyl) -3,4-dichlorobenzamide,
- N- (2-aminoethyl) -2,4-dichlorobenzamide or
- N- (2-aminoethyl) benzamide,
or pharmaceutically acceptable acid addition salts thereof.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1150/83A CH653670A5 (en) | 1983-03-03 | 1983-03-03 | BENZAMIDE DERIVATIVES. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3407654A1 DE3407654A1 (en) | 1984-09-06 |
| DE3407654C2 true DE3407654C2 (en) | 1994-04-07 |
Family
ID=4203649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3407654A Expired - Fee Related DE3407654C2 (en) | 1983-03-03 | 1984-03-01 | Use of benzamide derivatives |
Country Status (28)
| Country | Link |
|---|---|
| JP (1) | JPS59167552A (en) |
| KR (1) | KR910008202B1 (en) |
| AR (1) | AR243155A1 (en) |
| AT (1) | AT390948B (en) |
| AU (2) | AU570431B2 (en) |
| BE (1) | BE899059A (en) |
| CA (1) | CA1252794A (en) |
| CH (1) | CH653670A5 (en) |
| DE (1) | DE3407654C2 (en) |
| DK (1) | DK166382C (en) |
| ES (3) | ES8504680A1 (en) |
| FI (1) | FI79297C (en) |
| FR (1) | FR2541996B1 (en) |
| GB (1) | GB2135998B (en) |
| GR (1) | GR81866B (en) |
| HU (1) | HU193556B (en) |
| IE (1) | IE57004B1 (en) |
| IL (1) | IL71078A (en) |
| IT (1) | IT1173365B (en) |
| LU (1) | LU85231A1 (en) |
| MC (1) | MC1568A1 (en) |
| NL (1) | NL8400459A (en) |
| NO (1) | NO165999C (en) |
| NZ (1) | NZ207272A (en) |
| PH (1) | PH19623A (en) |
| PT (1) | PT78187B (en) |
| SE (1) | SE466447B (en) |
| ZA (1) | ZA841394B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1261335A (en) * | 1984-08-29 | 1989-09-26 | Hoffmann-La Roche Limited/Hoffmann-La Roche Limitee | Ethylenediamine monoamide derivatives |
| US4772630A (en) * | 1984-11-23 | 1988-09-20 | Ciba-Geigy Corp. | Benzamides and their salts |
| NZ219974A (en) * | 1986-04-22 | 1989-08-29 | Goedecke Ag | N-(2'-aminophenyl)-benzamide derivatives, process for their preparation and their use in the control of neoplastic diseases |
| FR2642972B1 (en) * | 1989-02-14 | 1994-08-05 | Inst Nat Sante Rech Med | AGENTS FOR THE DIAGNOSIS AND TREATMENT OF MELANOMAS, HALOGENATED AROMATIC DERIVATIVES SUITABLE FOR USE AS SUCH AGENTS AND THEIR PREPARATION |
| WO2014155184A1 (en) * | 2013-03-28 | 2014-10-02 | Rhenovia Pharma | Treatment for parkinson's disease |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3342679A (en) * | 1967-09-19 | Parts by weight of acid chloride to react with parts of amine in | ||
| FR6557M (en) * | 1967-06-20 | 1968-12-23 | Ile De France | |
| GB1455116A (en) * | 1972-12-15 | 1976-11-10 | Ici Ltd | Pharmaceutical compositions |
| GB1520584A (en) * | 1975-04-02 | 1978-08-09 | Yamanouchi Pharma Co Ltd | 2 - alkoxy - 5 substituted benzamide derivatives and their use in pharmaceutical compositions |
| DE2616486A1 (en) * | 1976-04-14 | 1977-11-03 | Basf Ag | Perylene tetracarboxylic acid diimide pigments - for use in paints, thermoplastics, etc. and as vat dyes |
| CA1206964A (en) * | 1980-11-12 | 1986-07-02 | Nobuo Shinma | Tetra-substituted benzene derivatives |
| DE3200258A1 (en) * | 1982-01-07 | 1983-07-21 | Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München | SUBSTITUTED 1-BENZOYL-2-PHENYLIMINO IMIDAZOLIDINE, THE ACID ADDITION SALTS THEREOF, METHOD FOR THE PRODUCTION THEREOF AND THE MEDICINAL PRODUCTS CONTAINING THE SAME |
| IL69997A0 (en) * | 1983-01-03 | 1984-01-31 | Miles Lab | Procainamide and n-acetylprocainamide immunogens,antibodies prepared therefrom,labeled conjugates,and the use of such antibodies and labeled conjugates in immunoassays |
| US4808624A (en) * | 1984-06-28 | 1989-02-28 | Bristol-Myers Company | Pharmacologically active substituted benzamides |
-
1983
- 1983-03-03 CH CH1150/83A patent/CH653670A5/en not_active IP Right Cessation
-
1984
- 1984-01-13 CA CA000445296A patent/CA1252794A/en not_active Expired
- 1984-02-13 NL NL8400459A patent/NL8400459A/en not_active Application Discontinuation
- 1984-02-22 FI FI840734A patent/FI79297C/en not_active IP Right Cessation
- 1984-02-23 IT IT19778/84A patent/IT1173365B/en active
- 1984-02-24 NZ NZ207272A patent/NZ207272A/en unknown
- 1984-02-24 ZA ZA841394A patent/ZA841394B/en unknown
- 1984-02-27 HU HU84767A patent/HU193556B/en not_active IP Right Cessation
- 1984-02-27 AU AU25066/84A patent/AU570431B2/en not_active Ceased
- 1984-02-27 IL IL71078A patent/IL71078A/en not_active IP Right Cessation
- 1984-02-29 PH PH30315A patent/PH19623A/en unknown
- 1984-02-29 LU LU85231A patent/LU85231A1/en unknown
- 1984-02-29 DK DK147584A patent/DK166382C/en not_active IP Right Cessation
- 1984-03-01 FR FR8403219A patent/FR2541996B1/en not_active Expired
- 1984-03-01 JP JP59037410A patent/JPS59167552A/en active Granted
- 1984-03-01 MC MC841696A patent/MC1568A1/en unknown
- 1984-03-01 GR GR73975A patent/GR81866B/el unknown
- 1984-03-01 DE DE3407654A patent/DE3407654C2/en not_active Expired - Fee Related
- 1984-03-02 AT AT0072484A patent/AT390948B/en not_active IP Right Cessation
- 1984-03-02 IE IE512/84A patent/IE57004B1/en not_active IP Right Cessation
- 1984-03-02 BE BE0/212488A patent/BE899059A/en not_active IP Right Cessation
- 1984-03-02 GB GB08405486A patent/GB2135998B/en not_active Expired
- 1984-03-02 PT PT78187A patent/PT78187B/en not_active IP Right Cessation
- 1984-03-02 AR AR84295901A patent/AR243155A1/en active
- 1984-03-02 ES ES530230A patent/ES8504680A1/en not_active Expired
- 1984-03-02 SE SE8401190A patent/SE466447B/en not_active IP Right Cessation
- 1984-03-02 NO NO840797A patent/NO165999C/en unknown
- 1984-03-03 KR KR1019840001083A patent/KR910008202B1/en not_active IP Right Cessation
- 1984-10-25 ES ES537046A patent/ES8506601A1/en not_active Expired
- 1984-10-25 ES ES537045A patent/ES537045A0/en active Granted
-
1987
- 1987-12-24 AU AU83079/87A patent/AU609758B2/en not_active Ceased
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1964516C3 (en) | 1-Substituted 3-propionyl-anilinopyrrolidines, process for their preparation and pharmaceuticals | |
| DE2558501C2 (en) | ||
| DE1643262C3 (en) | i-Phenoxy ^ -hydroxy-S-alklyaminopropane, process for their preparation and medicaments containing these compounds | |
| DE3530046A1 (en) | AETHYLENE DIAMINE MONOAMIDE DERIVATIVES | |
| DE2502993A1 (en) | AMINES, THE METHOD OF MANUFACTURING THEIR PRODUCTS AND THE MEDICINAL PRODUCTS CONTAINING THEY | |
| DE2818672A1 (en) | ALPHA- (1-R-3-AZETIDINYL) -ALPHA- PHENYL-ALPHA-SUBSTITUTED-ACETAMIDE OR ACETONITRILE, METHOD FOR THEIR MANUFACTURING AND USE FOR THE TREATMENT OF ARRHYTHMIA | |
| DE3407654C2 (en) | Use of benzamide derivatives | |
| DE1940566C3 (en) | 1- (2-Nitrilophenoxy) -2-hydroxy-3ethylaminopropane, process for its preparation and pharmaceuticals containing it | |
| CH631700A5 (en) | Method for producing new substituted diphenylsulfiden. | |
| DE2817083A1 (en) | BENZYLISOCHINOLINE DERIVATIVES, METHOD FOR THEIR MANUFACTURING AND MEDICINAL PREPARATIONS CONTAINING THESE COMPOUNDS | |
| DE2829471C2 (en) | ||
| DE3035688A1 (en) | 2-AMINO-3-BENZOYL-PHENYL ACETAMIDE DERIVATIVES, PHARMACEUTICAL PREPARATIONS THAT CONTAIN THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF | |
| CH637646A5 (en) | ANALGETICALLY ACTIVE TRIAZINDIONE, PRODUCTION PROCESS AND PHARMACEUTICAL COMPOSITIONS. | |
| DE2616403A1 (en) | METHOD FOR PREPARING DIASTEREOISOMER A BY RACEMIC SEPARATION OF 5 ANGULAR CLAMP ON 1-HYDROXY-2- (1-METHYL-3-PHENYLPROPYLAMINO) -AETHYL ANGLE CLAMP TO SALICYLAMIDE AND ARCENTDEAL | |
| DE1620295C3 (en) | Isoquinolo square bracket to 2.1 square bracket to benzo square bracket to 1.4 square bracket to diazepin-6-one | |
| CH635312A5 (en) | ALPHA-ARYL-ALPHA, ALPHA-BIS (OMEGA- (DISUBSTITUATED AMINO) -ALKYL) ACETAMIDES AND THEIR ACID ADDITION SALTS, METHOD FOR THE PRODUCTION THEREOF AND THE PRODUCT PREPARATIONS CONTAINING THEM. | |
| CH641167A5 (en) | N-Cyano-N'-(2-((4-methyl-5-imidazolyl)-methylthio)ethyl)-N''-alkyny l guanidines | |
| DE2705949C2 (en) | 4- (Benzoylamino) piperidine derivatives, a process for their preparation and pharmaceutical compositions containing them | |
| DE3004348C2 (en) | ||
| DE2127812C2 (en) | 3-Methyl-7-phenyl-5H-pyrimido [1,2-a] [1,4] benzodiazepin-1-ones and process for their preparation | |
| DE2530613A1 (en) | AMINE DERIVATIVES, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THEM | |
| DD202692A5 (en) | PROCESS FOR THE PREPARATION OF NEW DERIVATIVES OF 2-AMINO-AETHANOL | |
| EP0388739A1 (en) | Tetrahydronaphthalene derivates | |
| DE2009387C2 (en) | Aniline-acetamidines and their non-toxic acid addition salts, processes for their production and pharmaceutical preparations which contain these compounds | |
| DE2460304C2 (en) | 1-n-Propyl-4-phthalimido-piperidine-2,6-dione, process for its preparation and pharmaceuticals containing it |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8101 | Request for examination as to novelty | ||
| 8105 | Search report available | ||
| 8127 | New person/name/address of the applicant |
Owner name: F. HOFFMANN-LA ROCHE AG, BASEL, CH |
|
| 8128 | New person/name/address of the agent |
Representative=s name: LEDERER, F., DIPL.-CHEM. DR., 8000 MUENCHEN RIEDER |
|
| 8110 | Request for examination paragraph 44 | ||
| 8128 | New person/name/address of the agent |
Representative=s name: LEDERER, F., DIPL.-CHEM. DR., 8000 MUENCHEN RIEDER |
|
| 8125 | Change of the main classification |
Ipc: A61K 31/165 |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |