Aminoindane Derivatives As Serotonin And Norepinephrine Uptake Inhibitors

Abstract

The present invention relates to aminoindane derivatives having the formula I wherein X, Y, U, R 1-2 , and R 13-16 are as defined in the claims, or an acid addition salt thereof. The compounds of the invention posses the combined effect of serotonin reuptake inhibition and norepinephrine uptake inhibition.

1 - 7 . (canceled) 
     
     
         8 . A method for the treatment of an affective disorder in a living animal body, comprising administering a therapeutically effective amount of an aminoindane compound having the formula I: 
       
         
           
           
               
               
           
         
       
       Wherein:
 R 1  and R 2  are independently selected from hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalkyl; or R 1  and R 2  taken together with the nitrogen to which they are attached form a 3-7 membered: ring optionally containing one further heteroatom; 
 R 13 , R 14 , R 15  and R 16  are each independently selected from hydrogen, halogen, cyano, nitro, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, or C- 3-8 -cycloalkyl; 
 R is hydrogen, C 1-6 -alkyl or cyano; 
 X is —O—, —S— or —CR 4 R 5 —; 
 Y is —CR 6 R 7 —, —CR 6 R 7 —CR 8 R 9 — or —CR 6 ═CR 7 —; or X and Y taken together form a group —CR 4 ═CR 5 —, or —CR 4 ═CR 5 —CR 6 R 7 —; and 
 U is —O—, —S— or CR 10 R 11 ; 
 
       or
 X is —O—, —S— or —CR 4 R 5 —; and 
 Y and U taken together form a group CR 6 ═CR 7 —, —CR 6 ═CR 7 —CR 10 R 11 —, 
 or —CR 6 R 7 —CR 10 ═CR 11 —; 
 or X and Y and U taken together form —CR 4 ═CR 5 —CR 6 ═CR 7 —; 
 
       wherein:
 R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10  and R 11  are each independently selected form hydrogen or C 1-4 -alkyl; 
 or a pharmaceutically acceptable acid addition salt thereof. 
 
     
     
         9 . The method of  claim 8 , wherein the affective disorder is selected from the group consisting of depression and an anxiety disorder. 
     
     
         10 . The method of  claim 9 , wherein the anxiety disorder is selected from the group consisting of general anxiety disorder, social anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder, panic disorder, panic attacks, specific phobias, social phobia and agoraphobia. 
     
     
         11 . A method for the treatment of an affective disorder in a living animal body, comprising administering a therapeutically effective amount of a compound selected from the group consisting of:
 Trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   Trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-diethyl-amine,   Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-diethyl-amine,   Trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-ethyl-amine,   Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-ethyl-amine,   Trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-methyl-amine,   Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-methyl-amine,   (+)-trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   (−)-trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   (+)-cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   (−)-cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-dimethyl-amine,   Trans-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-ethyl-methyl-amine,   Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-ethyl-methyl-amine,   Cis-[3-(2,3-Dihydro-benzo[1,4]dioxin6-yl)-indan-1-yl]-dimethyl-amine,   Trans-[3-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-indan-1-yl]-dimethyl-amine,   Cis-Dimethyl-(3-naphthalen-2-yl-indan-1-yl)-amine,   Trans-Dimethyl-(3-naphthalen-2-yl-indan-1-yl)-amine,   Cis-[3-(6-Chloro-benzo[1,3]dioxol-5-yl)-indan-1-yl]-dimethyl-amine,   Cis-[3-(6-Chloro-benzo[1,3]dioxol-5-yl)-indan-1-yl]-dimethyl-amine,   Cis-[3-(6-Chloro-benzo[1,3]dioxol-5-yl)-indan-1-yl]-methyl-amine,   Trans-[3-(6-Chloro-benzo[1,3]dioxol-5-yl)-indan-1-yl]-methyl-amine,   (+)-Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-methyl-amine, and   (−)-Cis-(3-Benzo[1,3]dioxol-5-yl-indan-1-yl)-methyl-amine;   
       or a pharmaceutically acceptable acid addition salt thereof. 
     
     
         12 . The method of  claim 11 , wherein the affective disorder is selected from the group consisting of depression and an anxiety disorder. 
     
     
         13 . The method of  claim 12 , wherein the anxiety disorder is selected from the group consisting of general anxiety disorder, social anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder, panic disorder, panic attacks, specific phobias, social phobia and agoraphobia.