AT343643B - Verfahren zur herstellung von neuen naphthylsubstituierten ketonen - Google Patents

Verfahren zur herstellung von neuen naphthylsubstituierten ketonen

Info

Publication number
AT343643B
AT343643B AT501476A AT501476A AT343643B AT 343643 B AT343643 B AT 343643B AT 501476 A AT501476 A AT 501476A AT 501476 A AT501476 A AT 501476A AT 343643 B AT343643 B AT 343643B
Authority
AT
Austria
Prior art keywords
sep
naphthyl
methoxy
general formula
substituted
Prior art date
Application number
AT501476A
Other languages
English (en)
Other versions
ATA501476A (de
Original Assignee
Beecham Group Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Beecham Group Ltd filed Critical Beecham Group Ltd
Priority to AT501476A priority Critical patent/AT343643B/de
Publication of ATA501476A publication Critical patent/ATA501476A/de
Application granted granted Critical
Publication of AT343643B publication Critical patent/AT343643B/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/32—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions without formation of -OH groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
    • C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
    • C07C29/175—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds with simultaneous reduction of an oxo group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/60—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of -OH groups, e.g. by dehydration
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/28—Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/40—Halogenated unsaturated alcohols
    • C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/40—Halogenated unsaturated alcohols
    • C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
    • C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
    • C07C33/486—Polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C07C45/292—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups with chromium derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/62—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by hydrogenation of carbon-to-carbon double or triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C07C45/66—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C07C45/676—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/213—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C07C49/215—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/213—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C07C49/217—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C07C49/223—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the aromatic rings polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/227—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing halogen
    • C07C49/233—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C07C49/235—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description


   <Desc/Clms Page number 1> 
 



   Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von neuen, pharmazeutisch wirksamen naphthylsubstituierten Ketonen. 



   Es ist bekannt, dass   bestimmteNaphthalinderivate   wertvolle entzündungshemmende Wirksamkeit besitzen und daher zur Behandlung von verschiedenen rheumatischen und arthritischen Zuständen verwendet werden können. Ein besonders wirksames Naphthalinderivat, das klinische Anwendung gefunden hat, ist Naxopren der Formel 
 EMI1.1 
 
 EMI1.2 
 
Nr. l, 271,tiger Verbindungen sind auch in J. Med. Chem. 13, 203 (1970) und J. Pham. Exp. Thera., 179, 114 (1971) beschrieben. 



   Leider wurde festgestellt, dass die Verbindung der Formel (I) bei manchen Personen in einer Dosis, die 
 EMI1.3 
 ursacht. 



   Es wurde nun gefunden, dass andere Naphthalinderivate gute entzündungshemmende Wirksamkeit aufweisen, während sie in bezug auf die Magen-Darm-Reizung ein verbessertes therapeutisches Verhältnis besitzen. Derartige naphthylsubstituierte Ketone besitzen die allgemeine Formel 
 EMI1.4 
 worin X Chlor, Brom, Methoxy, Methylthio oder Alkyl mit 1 bis 4 C-Atomen bedeutet und    Rl   Wasserstoff oder Methyl ist. 



   In derartigen Verbindungen ist X am zweckmässigsten eine Methoxy- oder Methylthiogruppe, vorzugsweise eine Methoxygruppe. 



   Besonders geeignete Verbindungen der Formel (11) sind solche der allgemeinen Formel 
 EMI1.5 
 worin    R1   die oben angegebene Bedeutung hat. 
 EMI1.6 
 kung, wogegen solche, worin    R1   Wasserstoff ist, derartige Wirkungen mit geringerer Wahrscheinlichkeit zeigen. Demgemäss ist eine bevorzugte Verbindung   4- (6-Methoxy-2-naphthyl)-butan-2-on.   



   DieseVerbindung und ihr Analogon, worin das   o'-Kohlenstoffatom   einen Methylsubstituenten trägt, zeigten eine verlängerte entzündungshemmende Wirksamkeit, als sie in einer Dosis von 100 mg/kg/Tag gemäss dem   Ratten-Carageen-EntzUndungshemmungstest   geprüft wurden, jedoch den Magen in einer dreimal so hohen Dosis nicht reizten. 



   Die Verbindungen der allgemeinen Formel (II) können entzündungshemmenden und/oder analgetischen 

 <Desc/Clms Page number 2> 

 Zusammensetzungen, die zur oralen Verabreichung an Menschen gedacht sind, einverleibt werden. Derartige Zusammensetzungen können jede übliche Form aufweisen, wie Tabletten, Kapseln, Täschchen od. dgl. Einheitsdosisformen enthalten im allgemeinen 20 bis 100 mg, vorzugsweise 100 bis 600 mg des aktiven Bestandteiles der Formel (II). 



   Derartige Dosierungsformen können ein-oder mehrmals täglich (vorzugsweise zwei-bis viermal täglich) eingenommen werden, so dass die tägliche Dosis für einen 70 kg schweren Menschen gewöhnlich 300 bis 3000 mg, insbesondere 500 bis 2000 mg, beispielsweise 600 bis 1600 mg, beträgt. 



   Das erfindungsgemässe Verfahren zur Herstellung der neuen naphthylsubstituierten Ketone der allgemeinen Formel (II) besteht darin, dass man ein   s-Halogenalkylnaphthalin   der allgemeinen Formel 
 EMI2.1 
 worin   R1 und   X die oben angegebene Bedeutung haben, und    Bs Chlor,   Brom oder Jod bedeutet, mit einem von einem   ss-Diketon   stammenden Anion der allgemeinen Formel 
 EMI2.2 
 umsetzt. 



   Die Bildung des Anions der Formel (IV) kann vor der Umsetzung mit einer Verbindung der Formel (III) oder in situ stattfinden. Gewöhnlich wird die Reaktion in einem aprotischen Lösungsmittel, wie Äthylacetat, durchgeführt. 



   Es kann jede nicht extreme Temperatur angewendet werden, im allgemeinen wird jedoch Umgebungstemperatur oder erhöhte Temperatur bevorzugt, beispielsweise 20 bis 1200C. Die Reaktion kann sehr lang dauern, bis sie beendet ist. Wenn das Anion (IV) in situ gebildet wird, sollte zumindest 1 Äquivalent einer nichtnukleophilen Base vorhanden sein, beispielsweise Natriumhydrid, Natriumearbonat, Kaliumcarbonat od. dgl. 



   Pharmakologische Daten
Unter Anwendung eines herkömmlichen   Allen-Doisy-Tests   wurde die östrogene Wirksamkeit bestimmter erfindungsgemäss erhältlicher Verbindungen festgestellt. Die Ergebnisse sind in Tabelle I gezeigt. Die entzündungshemmende Wirksamkeit bestimmter erfindungsgemäss erhältlicher Verbindungen wurde unter Anwendung eines Standard-Rattenpfoten-Carrageen-Tests festgestellt. Diese Ergebnisse sind ebenfalls in Tabelle I gezeigt. 



   Diese Ergebnisse zeigen, dass die erfindungsgemäss erhältlichen Verbindungen in einer Dosierung ein gutes Ausmass an Aktivität aufweisen, wo eine übermässige Östrogenität nicht zu erwarten war. Weiterhin wird angenommen, dass das Fehlen einer Verzweigung am   o ;-Kohlenstoffatom jede Östrogenität   stark reduziert, die vorhanden sein könnte, während es die entzündungshemmende Wirksamkeit der Verbindungen nicht stark berührt. 



   Weiterhin wurde beobachtet, dass Verbindungen der Formel 
 EMI2.3 
 worin R1 die obige Bedeutung hat, den Rattenmagen in einer Dosis von 300 mg/kg/Tag bei oraler Verabreichung nach 3 Tagen nicht übermässig reizen, während am Ende einer 11/2 Tage dauernden oralen Behandlung mit der Verbindung der Formel (I) in der gleichen Dosis eine sehr schwere Magenreizung festgestellt wurde. 

 <Desc/Clms Page number 3> 

 
 EMI3.1 
 
 EMI3.2 
 
<tb> 
<tb> 



  Östrogenität <SEP> Entzilndungshemmung
<tb> Verbindung <SEP> Allen-Dolsy-Test <SEP> Ratten-Carrageen-Test <SEP> 
<tb> 3- <SEP> (6'-Methoxy-2'-naphthyl)- <SEP> 50 <SEP> mg/kg <SEP> subkutan, <SEP> inaktiv <SEP> 100 <SEP> mg/kg <SEP> oral,
<tb> butan-2-on <SEP> (Maus) <SEP> aktiv
<tb> 600 <SEP> mg/kg <SEP> oral, <SEP> inaktiv
<tb> (Ratte)
<tb> 3-Hydroxy-3-methyl-4- <SEP> (6'- <SEP> 100 <SEP> mg/kg <SEP> subkutan, <SEP> aktiv <SEP> 50 <SEP> und <SEP> 100 <SEP> mg/kg <SEP> oral,
<tb> methoxy-2'-naphthyl)-pen- <SEP> (Maus) <SEP> aktiv
<tb> tan-2-on
<tb> 4- <SEP> (6'-Methoxy-2'-naphthyl- <SEP> 300 <SEP> mg/kg <SEP> oral, <SEP> aktiv <SEP> 300 <SEP> mg/kg <SEP> oral,
<tb> pentan-2-on <SEP> (Ratte) <SEP> aktiv
<tb> 4- <SEP> (6'-Methoxy-2'-naphthyl)- <SEP> 200 <SEP> mg/kg <SEP> oral, <SEP> inaktiv <SEP> 50 <SEP> mg/kg <SEP> oral,
<tb> pentan-2-on <SEP> (Ratte)

   <SEP> schwach <SEP> aktiv
<tb> 100 <SEP> mg/kg <SEP> oral,
<tb> Aktivität <SEP> 1 <SEP> h <SEP> nachverabreichung <SEP> *)
<tb> 
 *) Aspirin (300 mg/kg) ergibt eine äquivalente Aktivität 2 h nach Verabreichung 
Das folgende Beispiel soll die Erfindung näher erläutern, ohne dass diese jedoch hierauf   beschränkt   sein soll. 



   Beispiel :4-(6-Methoxy-2-naphthyl)-butan-2-on
Eine Mischung 0, 1 Mol   6-Methoxy-2-brommethylnaphthylen,   0,1 Mol Acetylaceton und 0,1 Mol Kaliumcarbonat in 125 ml Äthanol wurden 16 h lang unter   Rückfluss   erhitzt. Das Äthanol wurde unter vermindertem Druck abgedampft und der Rückstand mit einer Mischung von Wasser und Äther (400 ml,   l : l)   geschüttelt. Die Ätherschicht wurde über MgS04 getrocknet und im Vakuum eingedampft, wobei ein klares Öl erhalten wurde, das nach Reinigung festes   4- (6-Methoxy-2-naphthyl)-butan-2-on   ergab.

Claims (1)

  1. PATENTANSPRUCH : Verfahren zur Herstellung von neuen naphthylsubstituierten Ketonen der allgemeinen Formel EMI3.3 worin X Chlor, Brom, Methoxy, Methylthio oder Alkyl mit 1 bis 4 C-Atomen bedeutet und R Wasserstoff oder Methyl ist, dadurch gekennzeichnet, dassmaneina-Halogenalkylnaphthalin der allgemeinen Formel EMI3.4 <Desc/Clms Page number 4> worin R und X die oben angegebene Bedeutung haben, und B3 Chlor, Brom oder Jod bedeutet, mit einem von einem ss-Diketon stammenden Anion der allgemeinen Formel EMI4.1 umsetzt.
AT501476A 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthylsubstituierten ketonen AT343643B (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT501476A AT343643B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthylsubstituierten ketonen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT501476A AT343643B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthylsubstituierten ketonen
AT9375A AT338257B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten

Publications (2)

Publication Number Publication Date
ATA501476A ATA501476A (de) 1977-10-15
AT343643B true AT343643B (de) 1978-06-12

Family

ID=3481320

Family Applications (8)

Application Number Title Priority Date Filing Date
AT501676A AT344152B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501476A AT343643B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthylsubstituierten ketonen
AT501876A AT343104B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501276A AT343642B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501576A AT343102B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501776A AT343103B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT9375A AT338257B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501176A AT344151B (de) 1975-01-08 1976-07-08 Verfahren zur herstellung von neuen naphthalinderivaten

Family Applications Before (1)

Application Number Title Priority Date Filing Date
AT501676A AT344152B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten

Family Applications After (6)

Application Number Title Priority Date Filing Date
AT501876A AT343104B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501276A AT343642B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501576A AT343102B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501776A AT343103B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT9375A AT338257B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten
AT501176A AT344151B (de) 1975-01-08 1976-07-08 Verfahren zur herstellung von neuen naphthalinderivaten

Country Status (1)

Country Link
AT (8) AT344152B (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8700354A (nl) * 1986-02-15 1987-09-01 Beecham Group Plc Nieuwe werkwijze.
EP0288144A3 (en) * 1987-03-26 1990-02-14 Beecham Group Plc 3-(6'-methoxy-2'-naphthylmethyl)-2,4 pentane dione, process for its preparation and intermediates

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2014993B (en) * 1977-11-03 1982-05-12 Beecham Group Ltd Chemical compounds
GB8603777D0 (en) * 1986-02-15 1986-03-19 Beecham Group Plc Chemical process
GB8603772D0 (en) * 1986-02-15 1986-03-19 Beecham Group Plc Process
AU5656698A (en) * 1996-12-03 1998-06-29 Recordati S.A. Chemical And Pharmaceutical Company A process for the preparation of nabumetone
DE202009002071U1 (de) 2009-04-17 2010-09-02 Paul Hettich Gmbh & Co. Kg Dämpfer für Möbel

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8700354A (nl) * 1986-02-15 1987-09-01 Beecham Group Plc Nieuwe werkwijze.
EP0288144A3 (en) * 1987-03-26 1990-02-14 Beecham Group Plc 3-(6'-methoxy-2'-naphthylmethyl)-2,4 pentane dione, process for its preparation and intermediates

Also Published As

Publication number Publication date
ATA501576A (de) 1977-09-15
AT343103B (de) 1978-05-10
AT338257B (de) 1977-08-10
AT344151B (de) 1978-07-10
ATA501876A (de) 1977-09-15
AT344152B (de) 1978-07-10
ATA9375A (de) 1976-12-15
ATA501776A (de) 1977-09-15
ATA501276A (de) 1977-10-15
AT343104B (de) 1978-05-10
AT343642B (de) 1978-06-12
ATA501176A (de) 1977-11-15
AT343102B (de) 1978-05-10
ATA501676A (de) 1977-11-15
ATA501476A (de) 1977-10-15

Similar Documents

Publication Publication Date Title
DE1643224C3 (de) 1 -Phenyl-2-aminoäthanolderivate und deren Säureadditionssalze, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE3046719C2 (de) 1,1,2-Triphenyl-but-1-en-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel
DE2257715C2 (de) N-substituierte 6-Methylen-6-desoxy-14-hydroxydihydronormorphinderivate
DE2807599C2 (de) Antiöstrogenes Mittel
DE2163911B2 (de) 2-Aminomethyl-phenole, Verfahren zur Herstellung derselben und diese enthaltende Arzneimittel
AT343643B (de) Verfahren zur herstellung von neuen naphthylsubstituierten ketonen
DE2304284C2 (de) 1,1-Diphenyläthylen-Derivate, Verfahren zu ihrer Herstellung und Arzneimittel
DE1901519A1 (de) Chinazolinylharnstoffe
DE3121175A1 (de) Erythro-1,2,3-triphenyl-1-pentanon-derivate sowie verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
DE1963317A1 (de) Chemische Verfahren und Produkte
DE1915230A1 (de) Hydroxyphenylalkylaminderivate und Verfahren zu deren Herstellung
DE2336671A1 (de) Oxyessigsaeureaether von o-thymotinsaeureestern
EP0000727B1 (de) 3-(4-(1,3-Diazacycloalken-2-yl)-phenyl)-1,2-benzisothiazole, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel.
DE1906322A1 (de) Neue alpha-Alkyl-5-hydroxytryptophanester
DE2931319A1 (de) 6-methoxy-2-acetylnaphthalinoxim- derivate, verfahren zu ihrer herstellung sowie sie enthaltende arzneimittel
DE2738131A1 (de) Aminoketone, verfahren zu ihrer herstellung und sie enthaltende arzneimittel
DE3008852A1 (de) Benzodiazepinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel
DE1902449C2 (de) Guanylhydrazon-Derivate, deren Herstellung und Verwendung als Pharmaka
DE2166662A1 (de) Tricyclische derivate von aliphatischen omega-alkoholen und verfahren zu ihrer herstellung
DE2053205A1 (de) Dihydrofurandenvate und Verfahren zu deren Herstellung
DE1951614C3 (de) Substituierte Benzylalkohol, deren physiologisch verträgliche Salze, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
AT357165B (de) Verfahren zur herstellung von neuen china- zolinderivaten und ihren salzen
AT343680B (de) Verfahren zur herstellung von neuen 1-(n-butyl)-3-alkyl -7- oxoalkylxanthinen
AT343645B (de) Verfahren zur herstellung von neuen indanylcarbonsauren und deren salzen
AT360990B (de) Verfahren zur herstellung des neuen 1-methyl-4- (3-carboxy-10,11-dihydro-5h-dibenzo-(a,d)- -cyclohepten-5-yliden)-piperidin (10,11-dihydro -3-carboxy-cyproheptadin), seines n-oxids und seiner salze

Legal Events

Date Code Title Description
ELA Expired due to lapse of time
ELJ Ceased due to non-payment of the annual fee