AT343104B - Verfahren zur herstellung von neuen naphthalinderivaten - Google Patents

Verfahren zur herstellung von neuen naphthalinderivaten

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Publication number
AT343104B
AT343104B AT501876A AT501876A AT343104B AT 343104 B AT343104 B AT 343104B AT 501876 A AT501876 A AT 501876A AT 501876 A AT501876 A AT 501876A AT 343104 B AT343104 B AT 343104B
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Austria
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group
sep
methoxy
derivatives
naphthalin
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AT501876A
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ATA501876A (de
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Beecham Group Ltd
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Description


   <Desc/Clms Page number 1> 
 



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



   Es istbekannt, 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 
 beschrieben. 



   Leider wurde festgestellt, dass die Verbindung der Formel (I) bei manchen Personen in einer Dosis, die nicht wesentlich höher istals die therapeutische Dosis, eine schwere Reizung des Magen-Darm-Traktes verursacht. 



   Es wurde nun gefunden, dass andere Naphthalinderivate gute entzündungshemmende Wirksamkeit aufwei- sen, währendsieinbezugaufdie Magen-Darm-Reizung ein verbessertes therapeutisches Verhältnis besitzen. 



   Derartige Verbindungen besitzen die allgemeine Formel 
 EMI1.3 
 worin X Chlor, Brom, Methoxy, Methylthio oder Alkyl mit 1 bis 4 C-Atomen bedeutet,    R   Wasserstoff oder Methyl ist und    At   eine Gruppe CO oder CHOH ist. 



   InderartigenVerbindungenistX am zweckmässigste eine Methoxy- oder Methylthiogruppe, vorzugsweise eine Methoxygruppe. 
 EMI1.4 
 
 EMI1.5 
 
 EMI1.6 
 

 <Desc/Clms Page number 2> 

 
 EMI2.1 
 worin R die obige Bedeutung hat. 



   Verbindungen der allgemeinen Formel (II), worin    R   Methyl ist, zeigen in hoher Dosis östrogene Wir- kungen, wogegen solche, worin    R1   Wasserstoff ist, derartige Wirkungen mit geringerer Wahrscheinlichkeit i zeigen. Demgemäss ist eine bevorzugte Verbindung   4- (6-Methoxy-2-naphthyl)-but-3-en-2-on.   



   Diese Verbindung und ihr Analogon, worin das a-Kohlenstoffatom einen Methylsubstituenten trägt, zeig- ten eine verlängerte entzündungshemmende Wirksamkeit, als sie in einer Dosis von 100 mg/kg/Tag gemäss   demRatten-Carrageen-Entzundungshemmungstest     geprüftwurden, jedochden   Magen in einer dreimal sohohen
Dosis nicht reizten. 



  Die   Verbindungen der allgemeinen Formel (II) können entzündungshemmenden   und/oder analgetischen Zu- sammensetzungen, die zur oralen Verabreichung an Menschen gedacht sind, einverleibt werden. Derartige
Zusammensetzungen können jede übliche Form aufweisen, wie Tabletten, Kapseln, Täschchen, od. dgL Ein- heitsdosisformen enthalten im allgemeinen 20 bis 100 mg, vorzugsweise 100 bis 600 mg des aktiven Bestand- teiles der Formel (II). Derartige Dosierungsformen können ein-oder mehrmals täglich (vorzugsweise zwei-   i   bis viermal täglich) eingenommen werden, so dass die tägliche Dosis für einen 70 kg schweren Menschen ge- wöhnlich 300 bis 3000 mg, insbesondere 500 bis 2000 mg, beispielsweise 600 bis 1600 mg, beträgt. 



   Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindungen der allgemeinen Formel (II) besteht darin, dass man eine Verbindung der allgemeinen Formel 
 EMI2.2 
 
 EMI2.3 
 

 <Desc/Clms Page number 3> 

 
 EMI3.1 
 worin Ri die obige Bedeutung hat, den Rattenmagen in einer Dosis von 300 mg/kg/Tag bei oraler Verabreichungnach 3 Tagen nicht übermässig reizen, während am Ende einer 1 1/2 Tage dauernden oralen Behandlung mit der Verbindung der Formel (I) in der gleichen Dosis eine sehr schwere Magenreizung festgestellt wurde. 



    Tabelle I    
 EMI3.2 
 
<tb> 
<tb> Verbindung <SEP> Östrogenität <SEP> Entzündungshemmung
<tb> Allen-Doisy-Test <SEP> Ratten-Carrageen-Test
<tb> 4- <SEP> (6'-Methoxy-2'-naphthyl)-100 <SEP> mg/kg <SEP> subkutan, <SEP> 100 <SEP> mg/kg <SEP> oral,
<tb> pent-3-en-2-on <SEP> inaktiv <SEP> (Maus) <SEP> aktiv
<tb> 4- <SEP> (6'-Methoxy-2'-naphthyl)-300 <SEP> mg/kg <SEP> oral, <SEP> 300 <SEP> mg/kg <SEP> oral,
<tb> 3-buten-2-on <SEP> inaktiv <SEP> (Ratte) <SEP> aktiv
<tb> 
 
Die folgenden Beispiele sollen die Erfindung näher erläutern, ohne dass diese jedoch hierauf beschränkt sein soll. 



     Beispiel 1 :   4-   (6-Methoxy-2-naphthyl)-3-buten-2-on  
30 g 6-Methoxy-2-naphthaldehyd wurden in 500 ml Aceton mit 10 ml 10%iger wässeriger Natriumhydroxydlösung xydlösung 3 Stunden lang gerührt. Dabei entsteht aus dem Aldehyd zunächst der Alkohol der Formel   (III),   der dann dehydratisiertwird. Die Lösungwurde angesäuert und mit Äther extrahiert. Die ätherische Lösung wur- de über MgSO 4 getrocknet und unter vermindertem Druck eingedampft, wobei 30 g eines Feststoffes erhal- ten wurden. Dieses unreine Material wurde auf einer Silikagelsäule unter Anwendung von Benzol als Eluie- rungsmittel gereinigt, wobei 15 g der im Titel genannten Verbindung erhalten wurden, Fp. 120 C. 



  Beispiel2 :4-(6'-Methoxy-2'-naphthyl)-pentan-2-ol
Zu einer Lösung von 2 g 4-   (6'-Methoxy-2'-naphthyl)-pentan-2-on   in 100 ml Methanol, in Eis gekühlt, wurde 1 g Natriumborhydrid zugesetzt. Die Lösung wurde 1 Stunde lang gerührt, mit verdünnter   HCI   ange- säuert und dreimal mit je 100 ml Äther extrahiert. Die mit Wasser gewaschenen Ätherextrakte wurden über wasserfreiem Na SO getrocknet und eingedampft, wobei 1, 3 g eines klaren farblosen Öls erhalten wurden. 



  IR : 3400   cm'   (OH). Keine   C=O-Absorption vorhanden.   
 EMI3.3 
 



   Das Oxydationsmittel wurde tropfenweise zugegeben, bis die orange Farbe bestehen blieb. Dünnschicht-   : chromatographie SllikageIplatten/ToluoI) zelgte, daB   die Reaktion vollständig war. Filtrieren der Lösung,
Abdampfen des Lösungsmittels und Kristallisation des Rückstandes aus Äthanol/Wasser ergab 330 mg 4- (6-   Methoxy-2-naphthyl (-butan : -2-on,   Fp.   79 C.

Claims (1)

  1. PATENTANSPRUCH : Verfahren zur Herstellung von neuen Naphthalinderivaten der allgemeinen Formel EMI3.4 <Desc/Clms Page number 4> EMI4.1 allgemeinen Formel EMI4.2 worin Xi die Gruppe X mit der oben angegebenen Bedeutung oder eine Hydroxylgruppe ist und R und Ai die oben angegebene Bedeutung haben, dehydratisiert wird, worauf, wenn die Gruppe X eine freie OH-Gruppe ist, diese zu einer Methoxygruppe methyliert und gegebenenfalls die Gruppe Ai mit der Bedeutung CO durch Reduktion in die Gruppe CHOH oder die Gruppe A mit der Bedeutung CHOH durch Oxydation in die Gruppe CO übergeführt wird.
AT501876A 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten AT343104B (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT501876A AT343104B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten

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AT501876A AT343104B (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

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ATA501876A ATA501876A (de) 1977-09-15
AT343104B true AT343104B (de) 1978-05-10

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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
AT501576A AT343102B (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
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
AT501876A AT343104B (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
AT501176A AT344151B (de) 1975-01-08 1976-07-08 Verfahren zur herstellung von neuen naphthalinderivaten

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Application Number Title Priority Date Filing Date
AT501676A AT344152B (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
AT501276A AT343642B (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
AT9375A AT338257B (de) 1975-01-08 1975-01-08 Verfahren zur herstellung von neuen naphthalinderivaten

Family Applications After (2)

Application Number Title Priority Date Filing Date
AT501776A AT343103B (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

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Families Citing this family (7)

* 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
GB8603768D0 (en) * 1986-02-15 1986-03-19 Beecham Group Plc Process
GB8603772D0 (en) * 1986-02-15 1986-03-19 Beecham Group Plc Process
GB8707200D0 (en) * 1987-03-26 1987-04-29 Beecham Group Plc Chemical 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

Also Published As

Publication number Publication date
ATA501576A (de) 1977-09-15
ATA501876A (de) 1977-09-15
ATA9375A (de) 1976-12-15
AT344152B (de) 1978-07-10
ATA501776A (de) 1977-09-15
ATA501676A (de) 1977-11-15
AT344151B (de) 1978-07-10
ATA501476A (de) 1977-10-15
AT343102B (de) 1978-05-10
AT338257B (de) 1977-08-10
AT343642B (de) 1978-06-12
AT343103B (de) 1978-05-10
AT343643B (de) 1978-06-12
ATA501276A (de) 1977-10-15
ATA501176A (de) 1977-11-15

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