Therapeutic agents

Abstract

Substituted cycloalkyl compounds with 3 to 6 carbon atoms in the ring, one carbon linked to each of two side groups R and R′, and pharmaceutically acceptable salts thereof in which R is phenyl optionally substituted by one or more halo substituents or R is naphthyl; and R′ is —[X—Y—S(O) m -Z-N—R 1 —R 2 ], wherein X is carbonyl or a carbon directly linked to each of a hydroxyl group and R 5 in which R 5 is H or alkyl, Y is an alkylene chain optionally substituted by one or more alkyl groups, m can be 0, 1 or 2, Z is an alkylene chain containing 2 to 5 carbon atoms optionally substituted by one or more alkyl groups, and R 1 and R 2 , which are the same or different, are H, alkyl, or arylalkyl, provided that when R 1 is benzyl, R 2 is H or methyl; have utility in the treatment of drug misuse or other addictive disorders.

1 ) Compounds of formula I  
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof in which 
 m is 0, 1 or 2;  
 n is 2, 3, 4 or 5;  
 X is carbonyl or a group of formula II  
                     
 in which R 5  is H or an alkyl group containing 1 to 4 carbon atoms;  
 Y is an alkylene chain containing 1 or 2 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;  
 Z is an alkylene chain containing 2 to 5 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;  
 R is phenyl optionally substituted by one or more halo substituents (for example fluoro, chloro, bromo or iodo) or R is naphthyl; and  
 R 1  and R 2 , which are the same or different, are H, a straight or branched chain alkyl group containing 1 to 4 carbon atoms, an arylalkyl group in which the alkyl group contains 1 to 3 carbon atoms, provided that when R 1  is benzyl, R 2  is H or methyl;  
 for use in the treatment of drug misuse or other addictive disorders.  
 
     
     
         2 ) The use of compounds of formula I as claimed in  claim 1  in which m is 0.1 or 2 and n is 3 or 4.  
     
     
         3 ) The use of compounds of formula I as claimed in any preceding claim in which X is carbonyl or a group of formula II in which R 5  is H.  
     
     
         4 ) The use of compounds of formula I as claimed in any preceding claim in which Y is methylene.  
     
     
         5 ) The use of compounds of formula I as claimed in any preceding claim in which Z is an alkylene chain containing 2,3 or 4 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms.  
     
     
         6 ) The use of compounds of formula I as claimed in any preceding claim in which Z is an alkylene chain containing 2,3 or 4 carbon atoms optionally substitited by one or more methyl groups.  
     
     
         7 ) The use of compounds of formula I as claimed in any preceding claim in which R is phenyl substituted by one or two chloro substituents or R is naphthyl.  
     
     
         8 ) The use of compounds of formula I as claimed in any preceding claim in which R is 3-chlorophenyl, 3,4-dichlorophenyl or 2-naphthyl.  
     
     
         9 ) The use of compounds of formula I as claimed in any preceding claim in which R 1  is an alkyl group containing 1 to 3 carbon atoms or is benzyl, and R 2  is an alkyl group containing 1 to 3 carbon atoms.  
     
     
         10 ) The use of compounds of formula I as claimed in any preceding claim in which R 1  and R 2  are both methyl or ethyl or R 1  is benzyl and R 2  is methyl.  
     
     
         11 ) The use of compounds of formula III  
       and pharmaceutically acceptable salts thereof in which 
 m is 0, 1 or 2;  
 n is 2, 3, 4 or 5;  
 X is carbonyl or a group of formula II  
                     
 in which R 5  is H or an alkyl group containing 1 to 4 carbon atoms;  
 Y is an alkylene chain containing 1 or 2 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;  
 Z is an alkylene chain containing 2 to 5 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms;  
 R 1  and R 2 , which are the same or different, are H, a straight or branched chain alkyl group containing 1 to 4 carbon atoms, an arylalkyl group in which the alkyl group contains 1 to 3 carbon atoms, provided that when R 1  is benzyl, R 2  is H or methyl;  
 and R 3  is halo, and R 4  is H or halo, or R 3  and R 4  together with the carbon atoms to which they are attached form a fused benzene ring.  
 
     
     
         12 ) The use of compounds of formula III as claimed in  claim 11  in which R 3  is chloro and R 1  is H, R 3  and R 4  are both chloro or R 3  and R 4  together with the carbon atoms to which they are attached form a fused benzene ring.  
     
     
         13 ) The use of compounds of formula III as claimed in any preceding claim in which R 3  is chloro situated in the 3-substitution position on the phenyl ring and R 4  is H, R 3  and R 4  are both chloro and are situated in the 3- and 4-substitution positions on the phenyl ring respectively, or R 3  and R 4  together with the phenyl ring to which they are attached form a 2-naphthyl group.  
     
     
         14 ) The use of compounds of formula I as claimed in  claim 1  which are: 
 1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[2-(dimethylamino)ethylthio]ethanone:    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[2-(dimethylamino)ethylsulphinyl]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[2-(dimethylamino)ethylsulphonyl]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[2-(diethylamino)ethylthio]ethanone;    2-[2-(N-benzyl-N-methylamino)ethylthio]-1-[1-(3,4-dichlorophenyl)cyclobutyl]-ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl)-2-[2-(dimethylamino)ethylthio]ethanol;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[3-(dimethylamino)propylthio]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[3-(dimethylamino)propyisulphonyl]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[3-(dimethylamino)propylthio]ethanol;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[3-(dimethylamino)-2-methylpropylthio]-ethanone;    2-[2-(dimethylamino)ethylthio]-1-[1-(2-naphthyl)cyclobutyl]ethanone;    1-[1-(3-chlorophenyl)cyclobutyll-2-[3-(dimethylamino)propylthio]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[4(dimethyl-amino)butylthio]ethanone;    1-[1-(3,4dichlorophenyl)cyclobutyl]2-[3-(dipropyl-amino)propylthio]ethanone;    1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-[3-(dimethylamino)-2-methylpropylthio]ethanol;    1-[1-(3,4-dichlorophenyl)cyclopentyl]-2-[3-(dimethylamino)propylthio]ethanone;    and pharmaceutically acceptable salts thereof in the form of individual enantiomers, racemates, or other mixtures of enantiomers.    
     
     
         15 ) Pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula I as claimed in  claim 1 , together with a pharmaceutically acceptable diluent or carrier.  
     
     
         16 ) A method of treating drug misuse or other addictive disorders which comprises the administration of a therapeutically effective amount of a compound of formula I as defined in any one of  claims 1  to  14  to a patient in need thereof.  
     
     
         17 ) A method of reducing cravings to food or an addictive substance in a mammal comprising administering an effective amount of a compound of formula I as defined in any one of  claims 1  to  14  to a mammal in need thereof.  
     
     
         18 ) A method as claimed in  claim 17  wherein the addictive substance is cocaine, amphetamine, nicotine, opiates, tobacco, alcohol or ecstasy.  
     
     
         19 ) The use of a compound of formula I as claimed in any of  claims 1  to  14  in the manufacture of a medicament for use in the treatment of drug misuse or other addictive disorders