Quinoline 3-amino chroman derivatives

Abstract

Quinoline 3-amino chroman derivatives and compositions containing such compounds are disclosed. Methods for using the quinoline 3-amino chroman derivatives and compositions containing such compounds in the treatment of serotonin disorders are disclosed. Also disclosed are processes for preparing quinoline 3-amino chroman derivatives.

1 . A method of treating a patient suspected of suffering from a serotonin-related disorder, comprising the step of administering to the patient a therapeutically effective amount of a compound of formula I:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.  
       
     
     
         2 . A method according to  claim 1 , wherein said serotonin-related disorder is depression, anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, attention deficit disorder, obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine addiction, alcohol addiction, or sexual dysfunction.  
     
     
         3 . The method of  claim 2  wherein said serotonin-related disorder is depression.  
     
     
         4 . A method of inhibiting serotonin uptake in a patient in need thereof, comprising the step of administering to the patient a therapeutically effective amount of the compound of formula I:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.  
       
     
     
         5 . A method of antagonizing 5-HT 1A  receptors in a patient in need thereof, comprising the step of administering to the patient a therapeutically effective amount of the compound of formula I:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.  
       
     
     
         6 . A method of treating a patient suspected of suffering from a serotonin disorder, comprising the step of administering to the patient a therapeutically effective amount of the compound of formula II:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.  
       
     
     
         7 . A method according to  claim 6 , wherein said serotonin disorder is depression, anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, attention deficit disorder, obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine addiction, alcohol addiction, or sexual dysfunction.  
     
     
         8 . The method of  claim 7  wherein said serotonin disorder is depression.  
     
     
         9 . A method of inhibiting serotonin uptake in a patient in need thereof, comprising the step of administering to the patient a therapeutically effective amount of the compound of formula II:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.  
       
     
     
         10 . A method of antagonizing 5-HT 1A  receptors in a patient in need thereof, comprising the step of administering to the patient a therapeutically effective amount of the compound of formula II:  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof;  
         wherein R 1  is hydrogen, alkyl having 1 to 6 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, or methylcyclobutyl;  
         R 2  is hydrogen or alkyl having 1 to 6 carbon atoms;  
         R 3  is hydrogen, fluoro, chloro, bromo, iodo, cyano at either the 5- or 6-position; and  
         n is an integer from 2 to 4.