Tropane-derivatives, their preparation and use

Abstract

Compounds of formula (a), (b), (c), or (d), or any mixture thereof, or a pharmaceutically-acceptable salt thereof; wherein R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or 2 -hydroxyethyl; R 3 is —CH 2 —X—R′, wherein X is O, S or NR″, wherein R″ is hydrogen or alkyl and R′ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, or —CO-akyl; R 4 is phenyl optionally substituted with halogen, CF 3 , CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl, or aryl: 3,4-methylenedioxyphenyl; benzyl optionally substituted with halogen, CF 3 , CH, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl, or aryl; heteroaryl optionally substituted with halogen, CF 3 , CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl, or aryl; or naphthyl optionally substituted with halogen, CF 3 , CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl, or aryl. The compounds are monoamine neurotransmitter, i.e., dopamine, serotonin, noradrenaline, reuptake inhibitors.

1 . A compound having the formula,  
       
         
           
           
               
               
           
         
       
       or any mixture thereof, or a pharmaceutically acceptable salt thereof;  
       wherein 
 R is hydrogen, methyl, ethyl or propyl;  
 R 3  is —CH 2 —X—R′, wherein X is O or S, wherein R′ is methyl, ethyl, propyl or cyclopropylmethyl, and  
 R 4  is phenyl which may be substituted one or more times with halogen.  
 
     
     
         2 . A compound of  claim 1  which is 
 2-methoxymethyl-3-(4-chlorophenyl)-tropane,  
 N-Normethyl-2-methoxymethyl-3-(4-chlorophenyl)-tropane,  
 2-ethyloxymethyl-3-(4-chlorophenyl)-tropane,  
 2-cyclopropylmethyloxymethyl-3-(4-chlorophenyl)-tropane, or  
 N-normethyl-2-cyclopropylmethyloxymethyl-3-(4-chlorophenyl)-tropane,  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         3 . A compound of  claim 1  which is 
 (1R,2R,3S)-2-methoxymethyl-3-(4-chlorophenyl)-tropane,  
 (1R,2R,3 S)-N-Normethyl-2-methoxymethyl-3-(4-chlorophenyl)-tropane,  
 (1R,2R,3S)-2-ethoxymethyl-3-(4-chlorophenyl)-tropane,  
 (1R,2R,3S)-N-Normethyl-2-ethoxymethyl-3-(4-chlorophenyl)-tropane,  
 (1R,2R,3S)-N-normethyl-2-cyclopropylmethyloxymethyl-3-(4-chlorophenyl)-tropane,  
 or a pharmaceutically acceptable addition salt thereof.  
 
     
     
         4 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable addition salt thereof, together with at least one pharmaceutically acceptable carrier or diluent.