DE102007022007A1 - Novel pharmaceuticals, process for their preparation and their use in the prophylaxis and therapy of CNS diseases and diabetes - Google Patents
Novel pharmaceuticals, process for their preparation and their use in the prophylaxis and therapy of CNS diseases and diabetes Download PDFInfo
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- DE102007022007A1 DE102007022007A1 DE102007022007A DE102007022007A DE102007022007A1 DE 102007022007 A1 DE102007022007 A1 DE 102007022007A1 DE 102007022007 A DE102007022007 A DE 102007022007A DE 102007022007 A DE102007022007 A DE 102007022007A DE 102007022007 A1 DE102007022007 A1 DE 102007022007A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
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Abstract
Die vorliegende Patentanmeldung betrifft neuartige Pharmazeutika, Verfahren zu ihrer Herstellung und ihre Verwendung in der Therapie von ZNS-Erkrankungen und Diabetes.The present patent application relates to novel pharmaceuticals, processes for their preparation and their use in the therapy of CNS diseases and diabetes.
Description
Die vorliegende Patentanmeldung betrifft neuartige Pharmazeutika der allgemeinen Formel I, Verfahren zu Ihrer Herstellung und ihre Verwendung in der Therapie von ZNS-Erkrankungen und Diabetes.The The present patent application relates to novel pharmaceuticals of the general formula I, process for their preparation and their use in the therapy of CNS diseases and diabetes.
Hintergrund und Stand der TechnikBackground and state of the art
Adamantan-Derivate, insbesondere 1-Amino-3,5-dimethyl-adamantan (auch bekannt als Memantine) sind bekannt als Alzheimer-Therapeutika. Ihre Wirksamkeit ist begrenzt, es gibt eine Reihe bekannter Nebenwirkungen. Weitere Entwicklungen, wie z. B. Donepezil, haben sich als unwirksam in der Therapie von Alzheimer erwiesen. Es gibt daher Bedarf an weiteren Alzheimer- und anderen ZNS-Therapeutika.Adamantane derivatives, in particular 1-amino-3,5-dimethyl-adamantane (also known as memantine) known as Alzheimer's therapeutics. Their effectiveness is limited There are a number of known side effects. Further developments, such as B. Donepezil, have proven ineffective in the therapy of Alzheimer's proved. There is therefore a need for other Alzheimer's and other CNS therapeutics.
Beschreibung der ErfindungDescription of the invention
Es
wurde nun gefunden, dass Verbindungen der allgemeinen Formel I in der einer der Reste R1-R10 für
eine
Gruppe -ONR11R12 oder
-CH2-ONR11R12 oder -(CH2)2-ONR11R12,
eine
Gruppe oder eine Gruppe
steht, worin R11 und R12 unabhängig
voneinander für ein Wasserstoffatom,
eine verzweigte
oder unverzweigte C1-C10-Alkylgruppe
eine
Gruppe -(CH2)n-(CO)m-(CH2)o-(S)p(CH2)q-R13
eine Gruppe -(CH2)-(NH)m-(CH2)o-(S)p-(CH2)q-R13
eine Gruppe -(CO)n-(NH)m-(CH2)o-(S)p-(CH2)q-R13
eine Gruppe -(CH2)n-(NH)m-(CH2)o-(SO2)p-(CH2)q-R13
stehen,
worin n für
0, 1 oder 2 steht
m für 0 oder 1 steht
o für
0 oder 1 steht
p für 0 oder 1 steht
q für
0, 1 oder 2 steht
R13 für
-CH3, -OH oder einen Aryl- oder Heteroarylrest
steht und worin die anderen Reste R1-R10 unabhängig voneinander für
ein Wasserstoffatom, eine Hydroxygruppe, eine Methoxygruppe, eine
Methyl- oder eine Ethylgruppe stehen
sowie deren optische Isomeren
und deren Salze mit physiologische verträglichen Gegenionen,
überraschenderweise
hervorragende Eignung als ZNS-Therapeutika aufweisen. Sie sind darüber
hinaus wirksam in der Therapie von Diabetes.It has now been found that compounds of general formula I in which one of the radicals R 1 -R 10 for
a group -ONR 11 R 12 or -CH 2 -ONR 11 R 12 or - (CH 2 ) 2 -ONR 11 R 12 ,
a group or a group
in which R 11 and R 12 independently of one another represent a hydrogen atom,
a branched or unbranched C 1 -C 10 alkyl group
a group - (CH 2 ) n - (CO) m - (CH 2 ) o - (S) p (CH 2 ) q -R 13
a group - (CH 2 ) - (NH) m - (CH 2 ) o - (S) p - (CH 2 ) q -R 13
a group - (CO) n - (NH) m - (CH 2 ) o - (S) p - (CH 2 ) q -R 13
a group - (CH 2 ) n - (NH) m - (CH 2 ) o - (SO 2 ) p - (CH 2 ) q -R 13
stand,
where n is 0, 1 or 2
m stands for 0 or 1
o stands for 0 or 1
p stands for 0 or 1
q stands for 0, 1 or 2
R 13 is -CH 3 , -OH or an aryl or heteroaryl radical and wherein the other radicals R 1 -R 10 are independently of one another a hydrogen atom, a hydroxy group, a methoxy group, a methyl or an ethyl group
and their optical isomers and their salts with physiologically compatible counterions,
surprisingly excellent suitability as CNS therapeutics. They are also effective in the treatment of diabetes.
Detaillierte Beschreibung der Erfindung und bevorzugte AusführungsformenDetailed description of the invention and preferred embodiments
Bei den Verbindungen der allgemeinen Formel I handelt es sich um Adamantan-Derivate. In den Verbindungen der allgemeinen Formel I steht einer der Reste R1-R10 für eine Gruppe -ONR11R12 oder -CH2-ONR11R12 oder -(CH2)2-ONR11R12 und die anderen Reste unabhängig voneinander für ein Wasserstoffatom, eine Hydroxygruppe, eine Methoxygruppe, eine Methyl- oder eine Ethylgruppe. Bevorzugt sind solche Verbindungen, bei denen mehr als fünf der Reste R1-R10 für Wasserstoffatome stehen. Besonders bevorzugt stehen die Gruppen R5 und R5 für Methylgruppen.The compounds of general formula I are adamantane derivatives. In the compounds of the general formula I, one of the radicals R 1 -R 10 is a group -ONR 11 R 12 or -CH 2 -ONR 11 R 12 or - (CH 2 ) 2 -ONR 11 R 12 and the other radicals are independent each other represents a hydrogen atom, a hydroxy group, a methoxy group, a methyl or an ethyl group. Preference is given to those compounds in which more than five of the radicals R 1 -R 10 are hydrogen atoms. Particularly preferably, the groups R 5 and R 5 are methyl groups.
Innerhalb
der Gruppen -ONR11R12 oder
-CH2-ONR11R12 oder -(CH2)2-ONR11R12 können
R11 und R12 für Wasserstoffatome
stehen. R11 und R12 können
auch für verzweigte oder unverzweigte C1-C10-Alkylgruppen, zum Beispiel Methyl, Ethyl,
Propyl, Butyl, Pentyl oder für eine
-CO-CH2-S-CH2-CH2R13 oder eine -CO-NH-CH2-CH2-CH2-R13 Gruppe stehen. R11 und
R12 können ferner auch für
eine -CH2-CH2-SO2-OH Gruppe stehen.Within the groups -ONR 11 R 12 or -CH 2 -ONR 11 R 12 or - (CH 2 ) 2 -ONR 11 R 12 , R 11 and R 12 can be hydrogen atoms. R 11 and R 12 can also be used for branched or unbranched C 1 -C 10 -alkyl groups, for example methyl, ethyl, propyl, butyl, pentyl or for a
-CO-CH 2 -S-CH 2 -CH 2 R 13 or a -CO-NH-CH 2 -CH 2 -CH 2 -R 13 group. R 11 and R 12 may also be a -CH 2 -CH 2 -SO 2 -OH group.
Bevorzugte Verbindungen sind solche, bei denen einer der Reste R11 oder R12 für einen Pentylrest stehen, und der zweite Rest für -CO-CH2-S-CH2-CH2R13 oder für -CO-NH-CH2-CH2-CH2-R13 steht. R13 kann dabei ein Methyl, ein Phenyl oder ein Pyridinylrest sein. Bevorzugt steht R13 für einen Pyridinylrest.Preferred compounds are those in which one of the radicals R 11 or R 12 is a pentyl radical, and the second radical is -CO-CH 2 -S-CH 2 -CH 2 R 13 or -CO-NH-CH 2 - CH 2 -CH 2 -R 13 stands. R 13 can be a methyl, a phenyl or a pyridinyl radical. Preferably, R 13 is a pyridinyl radical.
In einer besonders bevorzugten Ausführungsform der Erfindung steht einer der Reste R1-R10 für eine Gruppe oder eine GruppeIn a particularly preferred embodiment of the invention, one of the radicals R 1 -R 10 is a group or a group
Verwendungenuses
Die Verbindungen der allgemeinen Formel I können für die Behandlung von ZNS-Erkrankungen verwendet werden, beispielsweise für die Behandlung von Alzheimer, Parkinsons Disease, Demenz und Multipler Sklerose. Als NMDA-Rezeptorantagonist wirken sie in allen Krankheiten, die über den NMDA-Rezeptor vermittelt werden.The Compounds of the general formula I can be used for the treatment of CNS disorders are used, for example for the treatment of Alzheimer's, Parkinson's disease, dementia and multiple sclerosis. As NMDA receptor antagonist they act in all diseases mediated via the NMDA receptor become.
Die Verbindungen der allgemeinen Formel I wirken weiterhin bei der Behandlung von Depression, Glaukom, Tinitus und Neuropathien.The Compounds of general formula I continue to work in the treatment of depression, glaucoma, tinitus and neuropathies.
Bemerkenswert ist die weitere Eignung zur Behandlung von bestimmten Autoimmun-Erkrankungen, wie Lupus Erythematosus. Die Verbindungen zeigen darüber hinaus Wirksamkeit bei der Behandlung bakteriellen Erkrankungen (z. B. Malaria) und von von viralen Erkrankungen, wie z. B. Influenza, inklusive verschiedener Varianten der Vogelgrippe, wie z. B. A-H5N1.Remarkable is the further suitability for the treatment of certain autoimmune diseases, such as Lupus erythematosus. The connections show beyond that Efficacy in the treatment of bacterial diseases (eg. Malaria) and of viral diseases such. Influenza, including various variants of bird flu, such. B. A-H5N1.
Völlig überraschend sind die Verbindungen der allgemeinen Formel I auch bei der Behandlung von Diabetes wirksam.Completely surprising the compounds of general formula I are also in the treatment effective for diabetes.
Formulierungenformulations
Die vorliegende Erfindung lehrt eine pharmazeutische Zusammensetzung enthaltend mindestens eine erfindungsgemäße Verbindung. Optional können ein oder mehrere physiologisch verträgliche Hilfsstoffe und/oder Trägersstoffe mit der Verbindung gemischt und die Mischung galenisch zur lokalen oder systemischen Gabe, insbesondere oral, parenteral, zur Infusion, zur Injektion hergerichtet sein. Die Auswahl der Zusatz- und/oder Hilfsstoffe wird von der gewählten Darreichungsform abhängen. Die galenische Herrichtung der erfindungsgemäßen pharmazeutischen Zusammensetzung erfolgt in fachüblicher Weise. Als Gegenion für ionische Verbindungen kommen beispielsweise Ca+ +, Na+, K+, Li+ oder Cyclohexylammonium, bzw. Cl–, Br–, Azetat, Propionat, Laktat, Oxalat, Malonat, Maleinst, Citrat, Benzoat, Salizylat oder ähnliches in Frage. Geeignete feste oder flüssige galenische Zubereitungsformen sind beispielsweise Granulate, Pulver, Dragees, Tabletten, Mikrokapseln, Suppositorien, Sirupe, Säfte, Suspensionen, Emulsionen, Tropfen oder Lösungen zur Injektion (i. v., i. p., i. m., s. c.) oder Vernebelung (Aerosole), Zubereitungsformen zur Trockenpulverinhalation, transdermale Systeme sowie Präparate mit retardierter Wirkstofffreigabe, bei deren Herstellung übliche Hilfsmittel wie Trägerstoffe, Spreng-, Binde-, Überzugs-, Quellungs-, Gleit- oder Schmiermittel, Geschmacksstoffe, Süßungsmittel und Lösungsvermittler Verwendung finden. Als Hilfsstoffe seien beispielsweise Magnesiumkarbonat, Titandioxyd, Laktose, Manid und andere Zucker, Talkum, Milcheiweiß, Gelatine, Stärke, Zellulose und ihre Derivate, tierische und pflanzliche Öle wie Lebertran, Sonnenblumen-, Erdnuss- oder Sesamöl, Polyethylenglykole und Lösungsmittel wie etwa steriles Wasser und ein- oder mehrwertige Alkohole, beispielsweise Glyzerin, genannt.The present invention teaches a pharmaceutical composition containing at least one compound of the invention. Optionally, one or more physiologically acceptable excipients and / or carriers may be mixed with the compound and the mixture galenically prepared for local or systemic administration, especially orally, parenterally, for infusion, for injection. The choice of additives and / or adjuvants will depend on the chosen dosage form. The galenic preparation of the The pharmaceutical composition of the invention is carried out in the usual way. As the counter ion for the ionic compounds are, for example Ca + +, Na +, K +, Li + or cyclohexylammonium, and Cl -, Br -, acetate, propionate, lactate, oxalate, malonate, Maleinst, citrate, benzoate, salicylate or the like in Question. Suitable solid or liquid pharmaceutical preparation forms are, for example, granules, powders, dragees, tablets, microcapsules, suppositories, syrups, juices, suspensions, emulsions, drops or solutions for injection (iv, ip, im, sc) or nebulization (aerosols), forms of preparation for Dry powder inhalation, transdermal systems as well as preparations with sustained-release release, in the production of which conventional auxiliaries such as carriers, blasting agents, binders, coating substances, swelling or lubricants, flavorings, sweeteners and solubilizers are used. Examples of excipients which may be mentioned are magnesium carbonate, titanium dioxide, lactose, manidine and other sugars, talc, milk protein, gelatin, starch, cellulose and its derivatives, animal and vegetable oils such as cod liver oil, sunflower, peanut or sesame oil, polyethylene glycols and solvents such as sterile water and monohydric or polyhydric alcohols, for example glycerol.
Eine erfindungsgemäße pharmazeutische Zusammensetzung ist dadurch herstellbar, dass mindestens eine erfindungsgemäß verwendete Substanzkombination in definierter Dosis mit einem pharmazeutisch geeigneten und physiologisch verträglichen Träger und ggf. weiteren geeigneten Wirk-, Zusatz- oder Hilfsstoffen mit definierter Dosis gemischt und zu der gewünschten Darreichungsform hergerichtet ist.A inventive pharmaceutical composition is producible by at least one used according to the invention Substance combination in a defined dose with a pharmaceutically suitable and physiologically acceptable carriers and optionally other suitable active ingredients, additives or excipients with defined Dose mixed and to the desired dosage form is prepared.
Als Verdünnungsmittel kommen Polyglykole, Ethanol, Wasser und Pufferlösungen in Frage. Geeignete Puffersubstanzen sind beispielsweise N,N-Dibenzylethylendiamin, Diethanolamin, Ethylendiamin, N-Methylglukamin, N-Benzylphenethylamin, Diethylamin, Phosphat, Natriumbikarbonat und Natriumkarbonat. Es kann aber auch ohne Verdünnungsmittel gearbeitet werden.When Diluents include polyglycols, ethanol, water and Buffer solutions in question. Suitable buffer substances are for example N, N-dibenzylethylenediamine, diethanolamine, ethylenediamine, N-methylglucamine, N-benzylphenethylamine, diethylamine, phosphate, Sodium bicarbonate and sodium carbonate. But it can also be without a diluent to be worked.
Vorzugsweise wird die pharmazeutische Zusammensetzung in Dosierungseinheiten herstellt und verabreicht, wobei jede Einheit als aktiven Bestandteil eine definierte Dosis der erfindungsgemäßen Verbindung gemäß Formel I enthält. Bei festen Dosierungseinheiten wie Tabletten, Kapseln, Dragees oder Suppositorien kann diese Dosis 0,1–1.000 mg, bevorzugt 1–300 mg, und bei Injektionslösungen in Ampullenform 0,01–1.000 mg, vorzugsweise 1–100 mg, betragen.Preferably the pharmaceutical composition is in dosage units and administered, each unit as an active ingredient a defined dose of the compound of the invention according to formula I contains. For solid dosage units such as tablets, Capsules, dragees or suppositories can dose this 0.1-1000 mg, preferably 1-300 mg, and for injection solutions in the form of ampoules 0.01-1000 mg, preferably 1-100 mg.
Für die Behandlung eines Erwachsenen, 50–100 kg schweren, beispielsweise 70 kg schweren, Patienten sind beispielsweise Tagesdosen von 0,1–1.000 mg Wirkstoff, vorzugsweise 1–500 mg, indiziert. Unter Umständen können jedoch auch höhere oder niedrigere Tagesdosen angebracht sein. Die Verabreichung der Tagesdosis kann sowohl durch Einmalgabe in Form einer einzelnen Dosierungseinheit oder aber mehrerer kleinerer Dosierungseinheiten als auch durch Mehrfachgabe unterteilter Dosen in bestimmten Intervallen erfolgen.For the treatment of an adult, 50-100 kg heavy, for example 70 kg patients, for example, daily doses of 0.1-1000 mg active ingredient, preferably 1-500 mg, indicated. In certain circumstances however, higher or lower daily doses may be used to be appropriate. The administration of the daily dose can be carried out both by Single dose in the form of a single dosage unit or several smaller Dosage units as well as by multiple subdivided doses done at certain intervals.
Herstellungsverfahrenproduction method
1) Synthese von 3,5-Dimethyladamantyloxyamin1) Synthesis of 3,5-dimethyladamantyloxyamine
1.1) Synthese von 3,5-Dimethyladamantyloxyphthalimid1.1) Synthesis of 3,5-dimethyladamantyloxyphthalimide
5,55 mmol 3,5-Dimethylhydroxyadamanol werden unter Argonatmosphäre in 20 ml CH2Cl2 gelöst auf 0°C gekühlt und 5,55 mmol BF3·OEt2 zugegeben. Nach 30 min. Rühren bei 0°C werden 5,55 mmol N-Hydroxyphthalimid zugegeben und die Mischung auf Raumtemperatur erwärmt. Nach weiteren 12h Rühren wird die Mischung auf 100 ml Eiswasser gegeben, 3 mal mit 100 ml CH2Cl2 extrahiert, über Na2SO4 getrocknet, und das Lösungsmittel im Vakuum entfernt. 4,03 mmol 3,5-Dimethyladamantyloxyphthalimid werden als weißer Feststoff erhalten (73%).5.55 mmol of 3,5-dimethylhydroxyadamanol are dissolved under argon atmosphere in 20 ml of CH 2 Cl 2 , cooled to 0 ° C., and 5.55 mmol of BF 3 .OEt 2 are added. After 30 min. Stirring at 0 ° C, 5.55 mmol N-hydroxyphthalimide are added and the mixture warmed to room temperature. After a further 12 h of stirring, the mixture is added to 100 ml of ice-water, extracted 3 times with 100 ml of CH 2 Cl 2 , dried over Na 2 SO 4 , and the solvent removed in vacuo. 4.03 mmol of 3,5-dimethyladamantyloxyphthalimide are obtained as a white solid (73%).
1.2) Synthese von 3,5-Dimethyladamantyloxyamin1.2) Synthesis of 3,5-dimethyladamantyloxyamine
5,38
mmol 3,5-Dimethyladamantyloxyphthalimid werden in 25 ml/EtOH (1:1)
gelöst und bei Raumtemperatur 8,07 mmmol Hydrazinmonohydrat
zugegeben. Die Reaktionsmischung wird 12 h bei Raumtemperatur gerührt
und anschließend mit 100 ml. ges. Natriumhydrogencarbonatlösung
und 100 ml. ges. NaCl-Lösung gewaschen, über Na2SO4 getrocknet,
das Lösungsmittel im Vakuum entfernt und das Rtoihprodukt
mittels Flash-Chromatographie an Kieselgel (PE:EE = 1:1) aufgereinigt.
5,12 mmol 3,5-Dimethyladamantyloxyamin werden als gelbes Öl
erhalten (95%). (1H-NMR Spektrum: siehe
Die Herstellung der weiteren erfindungsgemäßen Verbindungen der allgemeinen Formel I erfolgt über die dem Fachmann bekannten Verfahren der organischen Chemie, wobei die Einführung der C-O-N-C bevorzugt, aber nicht ausschließlich) über die oben beschriebene Phthalimid-Zwischenstufe (oder deren Analoga) verläuft.The preparation of the other compounds of general formula I according to the invention takes place via the methods of organic chemistry known to those skilled in the art, the introduction of the CONC being preferred but not limited to the phthalimide intermediate (or its analogues) described above.
Mögliche
Reaktionswege hierzu werden in den
Die
Herstellung von tert.-Alkoxy-Aminen kann gemäß der
Literaturvorschrift (
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDE IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.
Zitierte Nicht-PatentliteraturCited non-patent literature
- - Hasan Palandoken et al., Tetrahedron Letters 46 (2005) 6667-6669 [0021] Hasan Palandoken et al., Tetrahedron Letters 46 (2005) 6667-6669 [0021]
Claims (11)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007022007A DE102007022007A1 (en) | 2007-05-08 | 2007-05-08 | Novel pharmaceuticals, process for their preparation and their use in the prophylaxis and therapy of CNS diseases and diabetes |
PCT/DE2008/000835 WO2008135041A1 (en) | 2007-05-08 | 2008-05-08 | Adamantyloxyamine derivatives and related compounds for use as nmda and/or dpp-4 modulators for the therapy of cns diseases and diabetes |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007022007A DE102007022007A1 (en) | 2007-05-08 | 2007-05-08 | Novel pharmaceuticals, process for their preparation and their use in the prophylaxis and therapy of CNS diseases and diabetes |
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DE102009019852A1 (en) | 2009-05-06 | 2010-11-11 | Schebo Biotech Ag | New polymer compound comprising amine structural elements, useful as synthetic resins, coatings, foams, liquid crystals, adhesives, paints, varnishes, composite materials, in cosmetics, and in polymer electronics |
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KR20040016849A (en) * | 2001-04-02 | 2004-02-25 | 파노라마 리서치, 인크. | Antioxidant nitroxides and nitrones as therapeutic agents |
CN100408556C (en) * | 2002-10-07 | 2008-08-06 | 加利福尼亚大学董事会 | Modulation of anxiety by blocking hydrolysis of arachidonoylethanolamide |
US6995183B2 (en) * | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
ITTO20030668A1 (en) * | 2003-09-02 | 2005-03-03 | Rotta Res Lab S P A O Ra Rottapharm | DERIVATIVES OF ADAMANTAN EQUIPPED WITH NEUROPROTECTIVE, ANTIDEPRESSIVE AND ANTI-ISCHEMIC ACTIVITY AND PROCEDURE FOR THEIR PREPARATION. |
UA89035C2 (en) * | 2003-12-03 | 2009-12-25 | Лео Фарма А/С | Hydroxamic acid esters and pharmaceutical use thereof |
WO2006090244A1 (en) * | 2005-02-22 | 2006-08-31 | Glenmark Pharmaceuticals S.A. | New adamantane derivatives as dipeptidyl, peptidase iv inhibitors, processes for their preparation, and pharmaceutical compositions containing them |
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2007
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Hasan Palandoken et al., Tetrahedron Letters 46 (2005) 6667-6669 |
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