Morphinan derivatives the quaternary ammonium salts thereof substituted in position 14, method for production and use thereof

Abstract

The present invention relates to a class of morphinan compounds and quaternary ammonium salts thereof, substituted in Position 14, which may be used as highly active analgesics or also as opioid antagonists. The present invention also relates to the pharmaceutically acceptable salts and easily produced derivatives thereof, a process for the production thereof and use thereof in the production of pharmaceutical specialities.

1 . Compounds of the formula (I) or (Ia),  
       
         
           
           
               
               
           
         
         in which the substituents have the following significance:  
         R 1 : C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 2 -C 6 -alkinyl; C 3 -C 16 -(cyclical saturated group)alkyl, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyl, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyl, where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyl, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl;  
         R 2 : C 4 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 2 -C 6 -alkinyl; C 3 -C 16 -(cyclical saturated group)alkyl, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyl, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyl, where alkinyl is C 2 -C 6 ; C 8 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyl, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -aklinyl; C 3 -C 6 -alkenoyl; C 3 -C 6 alkinoyl; C 9 -C 16 -arylalkenoyl, where aryl is C 6 -C 10 -aryl and alkenoyl is C 3 -C 6 -alkenoyl; C 9 -C 16 -arylalkinoyl, where aryl is C 6 -C 10 -aryl and alkinoyl is C 3 -C 6 -alkinoyl;  
         R 3 : hydrogen, C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; alkoxyalkyl, where alkoxy is C 1 -C 6 -alkoxy and alkyl is C 1 -C 6 -alkyl; CO 2 (C 1 -C 6 -alkyl); CO 2 H; CH 2 OH.  
         R 4 : hydrogen; hydroxy; C 1 -C 6 -alkyloxy; C 2 -C 10 -alkyloxyalkoxy, where alkyloxy is C 1 -C 4  and alkoxy is C 1 -C 6 -alkyloxy; C 2 -C 6 -alkenyloxy; C 2 -C 6 -alkinyloxy; C 3 -C 16 -(cyclical saturated group)alkyloxy, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyloxy, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyloxy where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyloxy, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyloxy, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyloxy, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl; C 1 -C 6 -alkanoyloxy; C 3 -C 6 -alkenoyloxy; C 3 -C 6 -alkinoyloxy; C 7 -C 16 -arylalkanoyloxy, where aryl is C 6 -C 10 -aryl and alkanoyloxy is C 2 -C 6 -alkanoyloxy; C 9 -C 16 -arylalkenoyloxy, where aryl is C 6 -C 10 -aryl and alkenoyloxy is C 3 -C 6 -alkenoyloxy; C 9 -C 16 -arylalkinoyloxy, where aryl is C 6 -C 10 -aryl and alkinoyloxy is C 3 -C 6 -aikinoyloxy;  
         R 5 : hydrogen; hydroxy; C 1 -C 6 -alkyloxy; C 2 -C 10 -alkyloxyalkoxy, where alkyloxy is C 1 -C 4  and alkoxy is C 1 -C 6 -alkyloxy; C 2 -C 6 -alkenyloxy; C 2 -C 6 -alkinyloxy; C 3 -C 16 -(cyclical saturated group)alkyloxy, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyloxy, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyloxy, where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyloxy, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyloxy, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyloxy, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl; C 2 -C 6 -alkanoyloxy; C 7 -C 16 -arylalkanoyloxy, where aryl is C 6 -C 10 -aryl and alkanoyloxy is C 2 -C 6 -alkanoyloxy;  
         X is oxygen;  
         wherein a single or double bond can be present between the carbon atoms of numbers 7 and 8,  
         wherein alkyl, alkenyl and alkinyl can each be branched or unbranched, aryl can be unsubstituted or mono-, di- or trisubstituted, independently in each case, with hydroxy, halogen, nitro, cyano, thiocyanato, trifluoromethyl, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, CO 2 H, CONH 2 , CO 2 (C 1 -C 3 -alkyl), CONH(C 1 -C 3 -alkyl), CON(C 1 -C 3 -alkyl) 2 , CO(C 1 -C 3 -alkyl); amino; (C 1 -C 3 -monoalkyl)amino, (C 1 -C 3 -dialkyl)amino; C 5 -C 6 -cycloalkylamino, (C 1 -C 3 -alkanoyl)amido, SH, SO 3 H, SO 3 (C 1 -C 3 -alkyl), SO 2 (C 1 -C 3 -alkyl), SO(C 1 -C 3 -alkyl), C 1 -C 3 -alkylthio or C 1 -C 3 -alkanoylthio,  
         wherein -(cyclical saturated group) is either preferably C 3 -C 10 -cycloalkyl or a heterocyclical group with 2 to 9 carbon atoms, containing further one or more heteroatoms,  
         with the exception of compounds where R 1  is methyl, R 2  is C 4 -C 6 -alkyl, R 3  is hydrogen or methyl, R 4  is hydroxy or methoxy and R 5  is hydroxy, methoxy or an oxygen atom bound to the carbon atom in the 5 th  position, when X is oxygen;  
         with the further exception of compounds where R 1  is cyclopropylmethyl and XR 2  is benzyloxy, when R 4  is oxygen or benzyloxy and R 5  is an oxygen atom bound to the carbon atom in the 5 th  position;  
         with the further exception of compounds where R 1  is cyclopropylmethyl and XR 2  is benzyloxy, when R 4  is oxygen, hydroxy or benzyloxy and R 5  is hydroxy or methoxy.  
       
     
     
         2 . Compounds of the formula (IA) or (IAa),  
       
         
           
           
               
               
           
         
       
       where the substituents have the following significance: 
 R 1 : C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 2 -C 6 -alkinyl; C 3 -C 16 -(cyclical saturated group)alkyl, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyl, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyl, where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyl, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 8 -alkinyl;  
 wherein the two substituents R 1  can be the same or different;  
 R 2 : C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 2 -C 6 -alkinyl; C 3 -C 16 -(cyclical saturated group)alkyl, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyl, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyl, where alkinyl is C 2 -C 6 ; C 8 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyl, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl; C 3 -C 6 -alkenoyl; C 3 -C 6 -alkinoyl; C 9 -C 16 -arylalkenoyl, where aryl is C 6 -C 10 -aryl and alkenoyl is C 3 -C 6 -alkenoyl; C 9 -C 16 -arylalkinoyl, where aryl is C 6 -C 10 -aryl and alkinoyl is C 3 -C 6 -alkinoyl;  
 R 3 : hydrogen, C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; alkoxyalkyl, where alkoxy is C 1 -C 6 -alkoxy and alkyl is C 1 -C 6 -alkyl; CO 2 (C 1 -C 6 -alkyl); CO 2 H; CH 2 OH.  
 R 4 : hydrogen; hydroxy; C 1 -C 6 -alkyloxy; C 2 -C 10 -alkyloxyalkoxy, where alkyloxy is C 1 -C 4  and alkoxy is C 1 -C 6 -alkyloxy; C 2 -C 6 -alkenyloxy; C 2 -C 6 -alkinyloxy; C 3 -C 16 -(cyclical saturated group)alkyloxy, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyloxy, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyloxy where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyloxy, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyloxy, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyloxy, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl; C 2 -C 6 -alkanoyloxy; C 3 -C 6 -alkenoyloxy; C 3 -C 6 -alkinoyloxy; C 8 -C 16 -arylalkanoyloxy, where aryl is C 6 -C 10 -aryl and alkanoyloxy is C 2 -C 6 -alkanoyloxy; C 9 -C 16 -arylalkenoyloxy, where aryl is C 6 -C 10 -aryl and alkenoyloxy is C 3 -C 6 -alkenoyloxy; C 9 -C 16 -arylalkinoyloxy, where aryl is C 6 -C 10 -aryl and alkinoyloxy is C 3 -C 6 -alkinoyloxy;  
 R 5 : hydrogen; hydroxy; C 1 -C 6 -alkyloxy; C 2 -C 10 -alkyloxyalkoxy, where alkyloxy is C 1 -C 4  and alkoxy is C 1 -C 6 -alkyloxy; C 2 -C 6 -alkenyloxy; C 2 -C 6 -alkinyloxy; C 3 -C 16 -(cyclical saturated group)alkyloxy, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyloxy, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyloxy, where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyloxy, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyloxy, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyloxy, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl; C 2 -C 6 -alkanoyloxy; C 7 -C 16 -arylalkanoyloxy, where aryl is C 6 -C 10 -aryl and alkanoyloxy is C 2 -C 6 -alkanoyloxy;  
 X is oxygen;  
 Y −  is I − , Br − , Cl − , OH −  or another pharmacologically acceptable counterion;  
 wherein a single or double bond can be present between the carbon atoms of numbers 7 and 8,  
 wherein alkyl, alkenyl and alkinyl can each be branched or unbranched, aryl can be unsubstituted or mono-, di- or trisubstituted, independently in each case, with hydroxy, halogen, nitro, cyano, thiocyanato, trifluoromethyl, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, CO 2 H, CONH 2 , CO 2 (C 1 -C 3 -alkyl), CONH(C 1 -C 3 -alkyl), CON(C 1 -C 3 -alkyl) 2 , CO(C 1 -C 3 -alkyl); amino; (C 1 -C 3 -monoalkyl)amino, (C 1 -C 3 -dialkyl)amino; C 5 -C 6 -cycloalkylamino, (C 1 -C 3 -alkanoyl)amido, SH, SO 3 H, SO 3 (C 1 -C 3 -alkyl), SO 2 (C 1 -C 3 -alkyl), SO(C 1 -C 3 -alkyl), C 1 -C 3 -alkylthio or C 1 -C 3 -alkanoylthio,  
 wherein -(cyclical saturated group) is either preferably C 3 -C 10 -cycloalkyl or a heterocyclical group with 2 to 9 carbon atoms, containing furthermore one or more heteroatoms.  
 
     
     
         3 . Compounds of the formulae (I) or (IA) of claims  1  or  2 , in which X is oxygen; R 1  is C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 4 -C 16 -cycloalkylalkyl, where cycloalkyl is C 3 -C 10  and alkyl is C 1 -C 6 ; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; R 2  is C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; R 3  is hydrogen or methyl; R 4  is hydroxy, methoxy or acetoxy.  
     
     
         4 . Compounds of the formula (IA) of  claim 2 , in which X is oxygen; R 1  is C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 4 -C 16 -cycloalkylalkyl, where cycloalkyl is C 3 -C 10  and alkyl is C 1 -C 6 ; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; R 2  is C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl, R 3  is hydrogen or methyl; R 4  is hydroxy, methoxy or acetoxy.  
     
     
         5 . Compounds of claims  1  or  2 , selected from: 17-allyl-4,5α-epoxy-3-methoxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-allyl-4,5α-epoxy-3-hydroxy-1 40-(3-phenylpropyloxy)morphinan-6-one, 17-allyl-4,5α-epoxy-3-methoxy-5β-methyl-1 4β-(3-phenylpropyloxy)morphinan-6-one, 17-allyl-4,5α-epoxy-3-hydroxy-5β-methyl-1 4β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclobutylmethyl-4,5α-epoxy-3-methoxy-14β-(3phenylpropyloxy)morphinan-6-one, 17-cyclobutylmethyl-4,5α-epoxy-3-hydroxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclobutylmethyl-4,5α-epoxy-3-methoxy-50-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclobutylmethyl-4,5α-epoxy-3-hydroxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 4,5α-epoxy-3-methoxy-5β,17-dimethyl-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-epoxy-3-hydroxy-5β,17-dimethyl-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 17-propyl-4,5α-epoxy-3-methoxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-propyl-4,5α-epoxy-3-hydroxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-propyl-4,5α-epoxy-3-methoxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-propyl-4,5α-epoxy-3-hydroxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-tetrahydrofurfuryl-4,5α-epoxy-3-methoxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-tetrahydrofurfuryl-4,5α-epoxy-3-hydroxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-tetrahydrofurfuryl-4,5α-epoxy-3-methoxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-tetrahydrofurfuryl-4,5α-epoxy-3-hydroxy-5-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-(2-phenylethyl)-4,5α-epoxy-3-methoxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-(2-phenylethyl)-4,5α-epoxy-3-hydroxy-14β-(3-phenylpropyloxy)morphinan-6-one, 17-(2-phenylethyl)-4,5α-epoxy-3-methoxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-(2-phenylethyl)-4,5α-epoxy-3-hydroxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-ethyl-4,5α-epoxy-3-methoxy-14β-(3phenylpropyloxy)morphinan-6-one, 17-ethyl-4,5α-epoxy-3-hydroxy-1 40-(3-phenylpropyloxy)morphinan-6-one, 17-ethyl-4,5α-epoxy-3-methoxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-ethyl-4,5α-epoxy-3-hydroxy-5β-methyl-14β-(3-phenylpropyloxy)morphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-[(2-methylbenzyl)oxy]morphinan-6-one, 14β-[(2-chlorobenzyl)oxy]-17-(cyclopropylmethyl)-4,5α-epoxy-3-hydroxymorphinan-6-one, 14β-benzyloxy-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxymorphinan-6-one, 1 4β-butoxy-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxymorphinan-6-one, 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-[(3-methylbutyl)oxy]morphinan-6-one, 4,5α-epoxy-5 β, 1 7-dimethyl-14β-[(3-phenylpropyl)oxy]-3-[(prop-2-inyl)oxy]morphinan-6-one, 1 4β-[(3-chlorobenzyl)oxy]-4,5α-epoxy-17-methyl-3-[(prop-2-inyl)oxy]morphinan-6-one, 4,5α-epoxy-17-ethyl-3-methoxy-1 4β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-epoxy-17-ethyl-3-hydroxy-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-epoxy-3-hydroxy-14β-[(3-methylbutyl)oxy]-17-propylmorphinan-6-one, 5β-benzyl-14-methoxycodeinone (=5-benzyl-7,8-didehydro-4,5α-epoxy-3,1 4β-dimethoxy-17-methyl-morphinan-6-one), 5β-benzyl-4,5α-epoxy-3,1 4β-dimethoxy-17-methylmorphinan-6-one, 5β-benzyl-4,5α-epoxy-3-hydoxy-1 4β-methoxy-1 7-methylmorphinan-6-one, 4-hydroxy-3-methoxy-17-methyl-14-[(3-phenylpropyl)oxy]-morphinan-6-one, 3,4-dimethoxy-17-methyl-14-[(3-phenylpropyl)oxy]-morphinan-6-one, 14β-benzyloxy-4-hydroxy-3-methoxy-17-methylmorphinan-6-one, 1 4β-benzyloxy-3,4-dimethoxy-1 7-methylmorphinan-6-one, 4-hydroxy-3-methoxy-17-methyl-1 4β-[(2-naphthylmethyl)oxy]morphinan-6-one, 3,4-dimethoxy-17-methyl-14β-[(2-naphthylmethyl)oxy]morphinan-6-one, 4-hydroxy-3-methoxy-5β, 1 7-dimethyl-14β-[(3-phenylpropyl)oxy]-morphinan-6-one, 3,4-dimethoxy-5,17-dimethyl-1 4β-[(3phenylpropyl)oxy]-morphinan-6-one, 14β-ethoxy-4-hydroxy-3-methoxy-5β,17-dimethylmorphinan-6-one, 14β-ethoxy-3,4-dimethoxy-5,17-dimethylmorphinan-6-one, 14β-benzyloxy-3,4-dimethoxy-5β,17-dimethylmorphinan-6-one, 4,5α-epoxy-3-hydroxy-17,17-dimethyl-6-oxo-14β-[(3-phenylpropyl)oxy]morphinanium-iodide, (17S)-4,5α-epoxy-17-ethyl-3-hydroxy-17-methyl-6-oxo-14β-[(3-phenylpropyl)oxy]morphinanium-iodide, (17R)-4,5α-epoxy-3-hydroxy-17-methyl-6-oxo-14β-[(3-phenylpropyl)oxy]-17-[(2(R,S)-tetrahydrofurfuran-2-yl)methyl]morphinanium-iodide, (17R)-17-allyl-4,5α-epoxy-14β-ethoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide, (17R)-17-allyl-4,5α-epoxy 3-hydroxy-14β-methoxy-17-methyl-6-oxomorphinanium-iodide, (17S)-17-allyl-4,5α-epoxy-3-hydroxy-14β-methoxy-17-methyl-6-oxomorphinanium-iodide, 4,5α-epoxy-3-hydroxy-14β-methoxy-17,17-dimethyl-6-oxo-morphinanium-iodide, 5β-benzyl-14β-(butyloxy)-4,5-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium-iodide, (17S)-17-allyl-5β-benzyl-14β-butoxy-4,5α-epoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide, 14β-butoxy-4,5α-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium-iodide, (17R)-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-17-methyl-6-oxo-14β-[(3-phenylpropyl)oxy]morphinanium-iodide, (17R)-17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-17-methyl-6-oxo-140-[(3-phenylpropyl)oxy]morphinanium-iodide, (17R)-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-17-methyl-6-oxo-14β-[(2-phenylbenzyl)oxy]morphinanium-iodide, (17R)-14β-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide, 17(R)-4,5α-epoxy-3-hydroxy-14β-methoxy-17-methyl-6-oxo-17-(2-phenylethyl)morphinanium-iodide, 4,5α-expoxy-3-methoxy-17-methyl-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-expoxy-3-methoxy-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-expoxy-3-hydroxy-17-methyl-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-expoxy-17-methyl-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 17-(cyclopropylmethyl)-4,5α-epoxy-14β-[(3-phenylpropyl)oxy]morphinan-6-one, 4,5α-epoxy-1 40-[(3-phenylpropyl)oxy]morphinan-6-one, 17-(cyclopropylmethyl)-4-hydroxy-1 40-[(3-phenylpropyl)oxy]morphinan-6-one, 17-(cyclopropylmethyl)-4-methoxy-1 40-[(3-phenylpropyl)oxy]morphinan-6-one, 4-(n-butyloxy)-17-(cyclopropylmethyl)-1 40-[(3-phenylpropyl)oxy]morphinan-6-one, or any pharmaceutically acceptable salt or easily accessible derivative of it.  
     
     
         6 . A pharmaceutical composition, comprising a compound of claims  1  or  2  and/or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier substance.  
     
     
         7 . (canceled)  
     
     
         8 . A method of using a compound of claims  1  or  2  for the treatment of pain, including chronic and acute pain, post-operative pain, rheumatic diseases (e.g. arthritis), ileus, obstipation, overweight, addiction, including opioid, cocaine and alcohol addiction as well as for the manufacture of a narcotic.  
     
     
         9 . Compounds according to  claim 1  or  2 , wherein R 5  is OH or alkoxy.  
     
     
         10 . Compounds according to  claim 1  or  2 , wherein R 3  is hydrogen, alkyl or aralkyl, preferably hydrogen or alkyl.  
     
     
         11 . Compounds according to  claim 1  or  2 , wherein R 4  is OH, alkoxy or alkenyloxy or alkinyloxy.  
     
     
         12 . Compounds according to  claim 1  or  2 , wherein a single bond is present between the carbon atoms of the numbers 7 and 8.  
     
     
         13 . Compounds according to  claim 1  or  2 , wherein R 2  is alkyl or aralkyl, preferably aralkyl.  
     
     
         14 . Compounds according to  claim 1  or  2 , wherein R 1  is alkyl, (cyclical saturated group)alkyl, aralkyl or alkenyl.  
     
     
         15 . Compounds according to  claim 1  or  2 , wherein R 1  is C 1 -C 6 -alkyl; C 2 -C 6 -alkenyl; C 2 -C 6 -alkinyl; C 3 -C 16 -(cyclical saturated group)alkyl, where alkyl is C 1 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkenyl, where alkenyl is C 2 -C 6 ; C 4 -C 16 -(cyclical saturated group)alkinyl, where alkinyl is C 2 -C 6 ; C 7 -C 16 -arylalkyl, where aryl is C 6 -C 10 -aryl and alkyl is C 1 -C 6 -alkyl; C 8 -C 16 -arylalkenyl, where aryl is C 6 -C 10 -aryl and alkenyl is C 2 -C 6 -alkenyl; C 8 -C 16 -arylalkinyl, where aryl is C 6 -C 10 -aryl and alkinyl is C 2 -C 6 -alkinyl.