Novel diazabicyclic aryl derivatives

Abstract

This invention relates to novel diazabicyclic aryl derivatives which are found to be cholinergic ligands at the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

1 . A diazabicyclic aryl derivative represented by Formula I 
     
       
         
         
             
             
         
       
       any of its enantiomers or any mixture of its enantiomers, or a prodrug, or a pharmaceutically-acceptable addition salt thereof, wherein 
       n is 1, 2 or 3; and 
       X and Y, independently of one another, represents CR 2 , CR 3  and/or N, wherein R 2  and R 3 , independently of one another, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, aryl-alkyl, heteroaryl and/or heteroaryloxy, which aryl, aryloxy, aryl-alkyl, heteroaryl and heteroaryloxy may optionally be substituted one or two times with halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl; and 
       R 1  represents 
       hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl or heteroaryl, which aryl or heteroaryl may optionally be substituted one or two times with alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, R′SO 2 NH— or (R′SO 2 ) 2 N—, wherein R′ represents hydrogen, alkyl, cycloalkyl, haloalkyl, alkenyl, phenyl or benzyl; or 
       a group of formula aryl-alkyl-, aryl-Z-(alkyl) m -, aryl-C≡C—, heteroaryl-Z-(alkyl) m - or heteroaryl-C≡C—, wherein
 m is 0 or 1; and 
 Z represents O or S; 
 and wherein the aryl and heteroaryl may optionally be substituted one or two times with alkyl, halo, haloalkyl, hydroxy, alkoxy, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, R′SO 2 NH— or (R′SO 2 ) 2 N—, wherein R′ represents hydrogen or alkyl; or 
 
       R 1  and R 2 , or R 1  and R 3 , together with the carbon atoms to which they are bound, form a benzo-fused aromatic carbocyclic ring, which benzo-fused aromatic carbocyclic ring may optionally be substituted one or two times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl. 
     
   
   
       2 . The diazabicyclic aryl of  claim 1 , wherein
 n is 1, 2 or 3.   
   
   
       3 . The diazabicyclic aryl derivative of  claim 1 , wherein
 aryl is selected from the group consisting of phenyl, indenyl and naphthyl; and   heteroaryl represents an aromatic 5- and 6-membered monocyclic heterocyclic group selected from the group consisting of furanyl, in particular furan-2- or 3-yl; thienyl, in particular thien-2- or 3-yl; pyrrolyl (azolyl), in particular pyrrol-2- or 3-yl; oxazolyl, in particular oxazol-2-, 4- or 5-yl; imidazolyl, in particular imidazol-2- or 4-yl; pyrazolyl, in particular pyrazol-1-, 3- or 4-yl; isoxazolyl, in particular isoxazol-3-, 4- or 5-yl; thiazolyl, in particular thiazol-2-, 4- or 5-yl, thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, pyridyl, in particular pyrid-2-, 3- or 4-yl; pyridazinyl, in particular pyridazin-3- or 4-yl; pyrimidinyl, in particular pyrimidin-2-, 4- or 5-yl; and pyrazinyl, in particular pyrazin-2- or 3-yl; or   an aromatic bicyclic heterocyclic group the group consisting of indolyl, in particular indol-2-, 3-, 5- or 6-yl, benzo[b]furanyl, in particular benzofuran-2-, 5- or 6-yl; benzo[b]thienyl, in particular benzothien-2-, 5- or 6-yl; benzoimidazolyl, in particular benzoimidazol-2-, 5- or 6-yl; quinolinyl, in particular quinolin-2-, 3-, 6- or 7-yl; isoquinolinyl, in particular isoquinolin-3-, 6- or 7-yl; and cinnolinyl, in particular cinnolin-6- or 7-yl.   
   
   
       4 . The diazabicyclic aryl derivative of  claim 1 , wherein
 aryl represents phenyl;   aryl-alkyl represents benzyl; and   heteroaryl represents furanyl, in particular furan-2- or 3-yl; imidazolyl, in particular imidazol-2- or 4-yl; isoxazolyl, in particular isoxazol-3-, 4- or 5-yl; thiazolyl, in particular thiazol-2-, 4- or 5-yl, thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, pyridyl, in particular pyrid-2-, 3- or 4-yl; or   indolyl, in particular indol-2-, 3-, 5- or 6-yl.   
   
   
       5 . The diazabicyclic aryl derivative of  claim 1 , wherein
 at least one of X and Y represents N; and   the other of X and Y represent CR 2 ;   and n, R 1  and R 2  are as defined in  claim 1 .   
   
   
       6 . The diazabicyclic aryl derivative of  claim 5 , which is
 (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-oxazolyl-5-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-(5-phenyl-oxazol-5-yl)-methanone; or   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-phenyl-1,3,4-oxadiazol-2-yl-methanone;   an enantiomers or a mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof.   
   
   
       7 . The diazabicyclic aryl derivative of  claim 1 , wherein
 one or two of R 2  and R 3 , independently of one another, represent hydrogen and/or halo; and   R 1  and the remainder of R 2  and R 3 , independently of one another, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, halo, CF 3 , OCF 3 , CN, nitro, phenyl, 2-nitro-phenyl, 2-nitro-4-methyl-phenyl, 3-nitro-phenyl, 4-nitro-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-halo-5-trifluoromethyl-phenyl, 2-amino-phenyl, 2-amino-4-methyl-phenyl, 3-amino-phenyl, 4-amino-phenyl, 2-amino-4-methyl-phenyl, 4-halo-phenyl, 4-formylamino-phenyl, 2-acetylamino-phenyl, 3-acetylamino-phenyl, 4-acetylamino-phenyl, N-3-phenyl-acetamide, N-4-phenyl-acetamide, N-4-phenyl-propionamide, N-4-phenyl-isobutyramide, N-4-phenyl-acrylamide, N-4-phenyl-benzamide, 4-(N,N-dimethyl-sulfonyl-amino)-phenyl, N-4-phenyl-2,2,2-trifluoro-acetamide trifluoro acetic acid, 4-phenyl-cyclopropanecarboxylic acid amide, 4-phenyloxy, 3,5-dihalo-phenyloxy, phenyl-ethynyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl-thiomethyl and/or 5-trifluoromethyl-2-pyridyl-thiomethyl.   
   
   
       8 . The diazabicyclic aryl derivative of  claim 1 , wherein
 both of X and Y represent CR 2 , CR 3  or N, wherein R 2  and R 3 , independently of one another, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl and/or heteroaryloxy, which aryl, aryloxy, heteroaryl and heteroaryloxy may optionally be substituted one or two times with halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl; or   X represents N or CR 2 , wherein R 2  represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl or heteroaryloxy, which aryl, aryloxy, heteroaryl or heteroaryloxy may optionally be substituted one or two times with halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl; and   Y represents N or CR 3 , wherein R 3  together with R′, and together with the carbon atoms to which they are bound, form a benzo-fused aromatic carbocyclic ring, which benzo-fused aromatic carbocyclic ring may optionally be substituted one or two times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl.   
   
   
       9 . The diazabicyclic aryl derivative of  claim 1 , represented by Formula II 
     
       
         
         
             
             
         
       
       any of its enantiomers or any mixture of its enantiomers, or a prodrug, or a pharmaceutically-acceptable addition salt thereof, wherein 
       n is 1, 2 or 3; and 
       X represents CR 4  or N, wherein R 4  represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl or heteroaryloxy, which aryl, aryloxy, heteroaryl or heteroaryloxy may optionally be substituted one or two times with halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, wherein R′ represents hydrogen or alkyl; 
       R 1  and R 2 , independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, phenyl, phenyloxy, heteroaryl and/or heteroaryloxy, which phenyl, phenyloxy, heteroaryl and heteroaryloxy may optionally be substituted one or two times with alkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, a group of the formula R′CONH—, R′SO 2 NH— and/or (R′SO 2 ) 2 N—, wherein R′ represents hydrogen, alkyl, cycloalkyl, haloalkyl, alkenyl, phenyl or benzyl; 
       wherein R′ represents hydrogen or alkyl; or 
       R 1  and R 2 , together with the carbon atoms to which they are bound, form a benzo-fused aromatic benzene ring, which benzene ring may optionally be substituted one or two times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl or heteroaryloxy, which aryl, aryloxy, heteroaryl or heteroaryloxy may optionally be substituted one or two times with halo, haloalkyl, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′ CONH—, wherein R′ represents hydrogen or alkyl. 
     
   
   
       10 . The diazabicyclic aryl derivative of  claim 9 , wherein
 R 1  represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkoxy, halo, CF 3 , OCF 3 , CN, nitro, phenyl, 2-nitro-phenyl, 2-nitro-4-methyl-phenyl, 3-nitro-phenyl, 4-nitro-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-halo-5-trifluoromethyl-phenyl, 2-amino-phenyl, 2-amino-4-methyl-phenyl, 3-amino-phenyl, 4-amino-phenyl, 2-amino-4-methyl-phenyl, 4-halo-phenyl, 4-formylamino-phenyl, 2-acetylamino-phenyl, 3-acetylamino-phenyl, 4-acetylamino-phenyl, N-3-phenyl-acetamide, N-4-phenyl-acetamide, N-4-phenyl-propionamide, N-4-phenyl-isobutyramide, N-4-phenyl-acrylamide, N-4-phenyl-benzamide, 4-(N,N-dimethyl-sulfonyl-amino)-phenyl, N-4-phenyl-2,2,2-trifluoro-acetamide trifluoro acetic acid, 4-phenyl-cyclopropanecarboxylic acid amide, 4-phenyloxy, 3,5-dihalo-phenyloxy, phenyl-ethynyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl-thiomethyl or 5-trifluoromethyl-2-pyridyl-thiomethyl;   R 2  represents hydrogen or halo; and   R 4  represents hydrogen, alkyl or halo.   
   
   
       11 . The diazabicyclic aryl derivative of  claim 1 , represented by Formula III 
     
       
         
         
             
             
         
       
       any of its enantiomers or any mixture of its enantiomers, or a prodrug, or a pharmaceutically-acceptable addition salt thereof, wherein 
       n is 1, 2 or 3; and 
       X represents CR 4  or N, wherein R 4  represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl or heteroaryloxy; 
       R 5  and R 6 , independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, cyanoalkyl, halo, haloalkyl, haloalkoxy, cyano, amino, nitro, aryl, aryloxy, heteroaryl or heteroaryloxy. 
     
   
   
       12 . The diazabicyclic aryl derivative of  claim 11 , wherein
 R 4  represents hydrogen or alkyl;   R 5  represents hydrogen, alkyl or alkoxy; and   R 6  represents hydrogen, alkyl or alkoxy.   
   
   
       13 . The diazabicyclic aryl derivative of  claim 11 , which is
 (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-8-methoxy-benzofuran-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-benzofuran-2-yl-methanone; or   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-3-methyl-benzofuran-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-benzooxazol-2-yl-methanone;   an enantiomers or a mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof.   
   
   
       14 . The diazabicyclic aryl derivative of  claim 1 , wherein
 R 1  represents a group of formula -(alkyl) m -Z-aryl, -(alkyl) m -Z-heteroaryl or —C≡C-aryl, wherein   m is 0 or 1; and   Z represents O or S;   and wherein the aryl and heteroaryl may optionally be substituted one or two times with alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, R′SO 2 NH— or (R′SO 2 ) 2 N—, wherein R′ represents hydrogen or alkyl.   
   
   
       15 . The diazabicyclic aryl derivative of  claim 14 , wherein
 R 1  represents a group of formula —CH 2 -Z-phenyl, —CH 2 -Z-pyridyl or —C≡C-phenyl, wherein   m is 0 or 1; and   Z represents O or S;   and wherein the phenyl and pyridyl group may optionally be substituted one or two times with alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cyano, amino, nitro and/or a group of the formula R′CONH—, R′SO 2 NH— or (R′SO 2 ) 2 N—, wherein R′ represents hydrogen or alkyl.   
   
   
       16 . The diazabicyclic aryl derivative of  claim 15 , which is
 (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3,5-dichlorophenoxy)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-[5-(trifluoromethyl-2-pyridyl)-thiomethyl]-furan-2-yl-methanone; or   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-phenylethynyl-furan-2-yl-methanone;   an enantiomers or a mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof.   
   
   
       17 . The diazabicyclic aryl of  claim 1 , wherein n is 2. 
   
   
       18 . The diazabicyclic aryl derivative of  claim 1 , wherein
 R 1  represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkoxy, halo, CF 3 , OCF 3 , CN, nitro, phenyl, 2-nitro-phenyl, 2-nitro-4-methyl-phenyl, 3-nitro-phenyl, 4-nitro-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-halo-5-trifluoromethyl-phenyl, 2-amino-phenyl, 2-amino-4-methyl-phenyl, 3-amino-phenyl, 4-amino-phenyl, 2-amino-4-methyl-phenyl, 4-halo-phenyl, 4-formylamino-phenyl, 2-acetylamino-phenyl, 3-acetylamino-phenyl, 4-acetylamino-phenyl, N-3-phenyl-acetamide, N-4-phenyl-acetamide, N-4-phenyl-propionamide, N-4-phenyl-isobutyramide, N-4-phenyl-acrylamide, N-4-phenyl-benzamide, 4-(N,N-dimethyl-sulfonyl-amino)-phenyl, N-4-phenyl-2,2,2-trifluoro-acetamide trifluoro acetic acid, 4-phenyl-cyclopropanecarboxylic acid amide, 4-phenyloxy, 3,5-dihalo-phenyloxy, phenyl-ethynyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl-thiomethyl or 5-trifluoromethyl-2-pyridyl-thiomethyl;   R 2  represents hydrogen, alkyl or halo; and   R 3  represents hydrogen, alkyl or halo.   
   
   
       19 . The diazabicyclic aryl derivative of  claim 18 , which is
 (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-bromo-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-nitro-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-(5-phenyl-furan-2-yl)-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-nitrophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3-trifluoromethylphenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-aminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-chlorophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-nitrophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3-nitrophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-acetylaminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-aminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3-aminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-acetylaminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3-acetylaminophenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-3-methyl-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-4,5-dibromo-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-chloro-5-trifluoromethylphenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-nitro-4-methylphenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(2-amino-4-methylphenyl)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-[4-(N,N-dimethylsulfonyl)aminophenyl]-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-formylaminophenyl)-furan-2-yl-methanone;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-propionamide;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(3,5-dichlorophenoxy)-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-[5-(trifluoromethyl-2-pyridyl)-thiomethyl]-furan-2-yl-methanone;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-2,2,2-trifluoro-acetamide trifluoro acetic acid;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-3-bromo-furan-2-yl-methanone;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-phenylethynyl-furan-2-yl-methanone;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-acrylamide;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-benzamide;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-[4-(N,N-diphenylsulfonylamino)phenyl]-furan-2-yl-methanone;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-isobutyramide;   Cyclopropanecarboxylic acid {4-[5-(1,4-diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-amide;   (1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-(4-aminophenyl)-furan-2-yl-methanone;   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-acrylamide N-oxide; or   N-{4-[5-(1,4-Diaza-bicyclo[3.2.2]nonane-4-carbonyl)-furan-2-yl]-phenyl}-acrylamide;   an enantiomers or a mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof.   
   
   
       20 . A pharmaceutical composition comprising a therapeutically effective amount of a diazabicyclic aryl derivative of  claim 1 , or a pharmaceutically-acceptable addition salt thereof, together with at least one pharmaceutically-acceptable carrier or diluent. 
   
   
       21 . A method of treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disorder, disease or condition is responsive to modulation of cholinergic receptors, which method comprises the step of administering to such a living animal body in need thereof a therapeutically effective amount of a diazabicyclic aryl derivative of any one of  claim 1 . 
   
   
       22 . The method according to  claim 21 , wherein the disease, disorder or condition relates to the central nervous system. 
   
   
       23 . The method according to  claim 22 , wherein the disease, disorder or condition is anxiety, cognitive disorders, learning deficit, memory deficits and dysfunction, Alzheimer's disease, attention deficit, attention deficit hyperactivity disorder, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Gilles de la Tourette's syndrome, depression, mania, manic depression, schizophrenia, obsessive compulsive disorders (OCD), panic disorders, eating disorders such as anorexia nervosa, bulimia and obesity, narcolepsy, nociception, AIDS-dementia, senile dementia, periferic neuropathy, autism, dyslexia, tardive dyskinesia, hyperkinesia, epilepsy, bulimia, post-traumatic syndrome, social phobia, sleeping disorders, pseudodementia, Ganser's syndrome, pre-menstrual syndrome, late luteal phase syndrome, chronic fatigue syndrome, mutism, trichotillomania and jet-lag. 
   
   
       24 . The method according to  claim 21 , wherein the disease, disorder or condition are associated with smooth muscle contractions, including convulsive disorders, angina pectoris, premature labour, convulsions, diarrhea, asthma, epilepsy, tardive dyskinesia, hyperkinesia, premature ejaculation and erectile difficulty. 
   
   
       25 . The method according to  claim 21 , wherein the disease, disorder or condition is related to the endocrine system, such as thyrotoxicosis, pheochromocytoma, hypertension and arrhythmias. 
   
   
       26 . The method according to  claim 21 , wherein the disease, disorder or condition is a neurodegenerative disorders, including transient anoxia and induced neuro-degeneration. 
   
   
       27 . The method according to  claim 21 , wherein the disease, disorder or condition is an inflammatory disorder, including inflammatory skin disorders such as acne and rosacea, Chron's disease, inflammatory bowel disease, ulcerative colitis and diarrhea. 
   
   
       28 . The method according to  claim 21 , wherein the disease, disorder or condition is mild, moderate or even severe pain of acute, chronic or recurrent character, as well as neuropathic pain and pain caused by migraine, postoperative pain, phantom limb pain, neuropathic pain, chronic headache, central pain, pain related to diabetic neuropathy, to post therapeutic neuralgia, or to peripheral nerve injury. 
   
   
       29 . The method according to  claim 21 , wherein the disease, disorder or condition is associated with withdrawal symptoms caused by termination of use of addictive substances, including nicotine containing products such as tobacco, opioids such as heroin, cocaine and morphine, benzodiazepines and benzodiazepine-like drugs and alcohol. 
   
   
       30 . (canceled)