Therapeutic Heterocyclic Compounds 507

Abstract

Provided herein is a compound having the formula (I): Wherein said compounds are useful for the treatment of psychiatric disorders including but not limited to depression, generalized anxiety, eating disorders, dementia, panic disorder, and sleep disorders. The compounds may also be useful in the treatment of gastrointestinal disorders, cardiovascular regulation, motor disorders, endocrine disorders, vasospasm and sexual dysfunction. The compounds are 5 HT 1B and 5 HT 1D antagonists.

1 - 9 . (canceled)  
     
     
         10 . A method of treating migraine in a mammal or human in need of such treatment comprising administering to the mammal or human an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is halogen or methoxy when positioned at the 6 th  position of the bicyclic ring, and is hydrogen, methyl, ethyl or methoxy when positioned at the 5 th  position of the bicyclic ring, and is hydrogen when positioned at the 7 th  position of the bicyclic ring;  
         R 2  is methyl piperazine;  
         R 6  is hydrogen;  
         Y is —C(═O)NH—;  
         R 7  is phenyl substituted with R 8 -R 9 ;  
         R 8  is a single bond as tether;  
         R 9  is a morpholinyl or piperazinyl attached to R 8  by nitrogen and optionally substituted on the other nitrogen (for piperazinyl) with R 11 ;  
         R 11  is AOH or —SO 2 A wherein A is represented by methyl or ethyl,  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         11 . A method of treating depression in a mammal or human in need of such treatment comprising administering to the mammal or human an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is halogen or methoxy when positioned at the 6 th  position of the bicyclic ring, and is hydrogen, methyl, ethyl or methoxy when positioned at the 5 th  position of the bicyclic ring, and is hydrogen when positioned at the 7 th  position of the bicyclic ring;  
         R 2  is methyl piperazine;  
         R 6  is hydrogen;  
         Y is —C(═O)NH—;  
         R 7  is phenyl substituted with R 8 -R 9 ;  
         R 8  is a single bond as tether;  
         R 9  is a morpholinyl or piperazinyl attached to R 8  by nitrogen and optionally substituted on the other nitrogen (for piperazinyl) with R 11 ;  
         R 11  is AOH or —SO 2 A wherein A is represented by methyl or ethyl,  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         12 . A method of treating generalized anxiety in a mammal or human in need of such treatment comprising administering to the mammal or human an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is halogen or methoxy when positioned at the 6 th  position of the bicyclic ring, and is hydrogen, methyl, ethyl or methoxy when positioned at the 5 th  position of the bicyclic ring, and is hydrogen when positioned at the 7 th  position of the bicyclic ring;  
         R 2  is methyl piperazine;  
         R 6  is hydrogen;  
         Y is —C(═O)NH—;  
         R 7  is phenyl substituted with R 8 -R 9 ;  
         R 8  is a single bond as tether;  
         R 9  is a morpholinyl or piperazinyl attached to R 8  by nitrogen and optionally substituted on the other nitrogen (for piperazinyl) with R 11 ;  
         R 11  is AOH or —SO 2 A wherein A is represented by methyl or ethyl,  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         13 . A method of treating panic disorder in a mammal or human in need of such treatment comprising administering to the mammal or human an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is halogen or methoxy when positioned at the 6 th  position of the bicyclic ring, and is hydrogen, methyl, ethyl or methoxy when positioned at the 5 th  position of the bicyclic ring, and is hydrogen when positioned at the 7 th  position of the bicyclic ring;  
         R 2  is methyl piperazine;  
         R 6  is hydrogen;  
         Y is —C(═O)NH—;  
         R 7  is phenyl substituted with R 8 -R 9 ;  
         R 8  is a single bond as tether;  
         R 9  is a morpholinyl or piperazinyl attached to R 8  by nitrogen and optionally substituted on the other nitrogen (for piperazinyl) with R 11 ;  
         R 11  is AOH or —SO 2 A wherein A is represented by methyl or ethyl,  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         14 . A method of treating dementia, eating disorders, sleep disorders, gastrointestinal disorders, motor disorders, endocrine disorders, vasospasm and sexual dysfunction in a mammal or human in need of such treatment comprising administering to the mammal or human an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is halogen or methoxy at the 6 th  position of the bicyclic ring, and is hydrogen, methyl, ethyl or methoxy at the 5 th  position of the bicyclic ring, and is hydrogen at the 7 th  position of the bicyclic ring;  
         R 2  is methyl piperazine;  
         R 6  is hydrogen;  
         Y is —C(═O)NH—;  
         R 7  is phenyl substituted with R 8 -R 9 ;  
         R 8  is a single bond as tether;  
         R 9  is a morpholinyl or piperazinyl attached to R 8  by nitrogen and optionally substituted on the other nitrogen (for piperazinyl) with R 11 ;  
         R 11  is AOH or —SO 2 A wherein A is represented by methyl or ethyl,  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         15 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is dementia.  
     
     
         16 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is eating disorder.  
     
     
         17 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is sleep disorder.  
     
     
         18 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is gastrointestinal disorders.  
     
     
         19 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is motor disorders.  
     
     
         20 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is endocrine disorders.  
     
     
         21 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is vasospasm.  
     
     
         22 . A method of treating a mammal or human in accordance with  claim 14  wherein the disease is sexual dysfunction.