Naphthyl(ethyl) acetamides

Abstract

This disclosure relates to novel melatonin analogues or naphthyl(ethyl)acetamides, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a dual melatoninergic agonist and serotoninergic antagonist.

1 . A compound of the Formula A: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is selected from H and CD 3 ; 
 R2 is selected from OH, H, D and F; 
 each of R 3a , R 3b , R 4a , and R 4b  is independently selected from H and D; 
 R 5  is selected from CH 3  and CD 3 ; and 
 at least one R comprises a deuterium atom. 
 
   
   
       2 . The compound of  claim 1 , wherein R 1  is H. 
   
   
       3 . The compound of  claim 1 , wherein R 1  is CD 3 . 
   
   
       4 . The compound of  claim 1 , wherein R 2  is selected from H and D. 
   
   
       5 . The compound of  claim 1 , wherein each R 3  is the same. 
   
   
       6 . The compound of  claim 1 , wherein each R 4  is the same. 
   
   
       7 . The compound of  claim 1 , wherein R 5  is CH 3 . 
   
   
       8 . The compound of  claim 1 , wherein R 5  is CD 3 . 
   
   
       9 . The compound of  claim 1 , selected from any one of the compounds in the table below: 
     
       
         
               
               
               
               
               
               
             
                   
               
                   
                   
                   
                 Each 
                 Each 
                   
               
                 Cmpd 
                 R 1   
                 R 2   
                 R 3   
                 R 4   
                 R 5   
               
                   
               
                 101 
                 CD 3   
                 H 
                 H 
                 H 
                 CH 3   
               
                 102 
                 CD 3   
                 D 
                 H 
                 H 
                 CH 3   
               
                 103 
                 H 
                 D 
                 H 
                 H 
                 CH 3   
               
                 104 
                 CD 3   
                 OH 
                 H 
                 H 
                 CH 3   
               
                 105 
                 CD 3   
                 F 
                 H 
                 H 
                 CH 3   
               
                   
               
           
              
              
              
              
             
             
              
              
              
              
              
              
             
          
         
       
     
     The compound of  claim 9 , wherein the compound is: 
     
       
         
         
             
             
         
       
     
   
   
       10 . The compound of  claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance. 
   
   
       11 . A compound of the formula 
     
       
         
         
             
             
         
       
     
   
   
       12 . A compound of the formula 
     
       
         
         
             
             
         
       
     
   
   
       13 . A pyrogen-free composition comprising a compound of  claim 1 ; and an acceptable carrier. 
   
   
       14 . The composition of  claim 13 , wherein the composition is suitable for pharmaceutical administration and said carrier is a pharmaceutically acceptable carrier. 
   
   
       15 . The composition of  claim 13 , additionally comprising a second therapeutic agent. 
   
   
       16 . The composition of  claim 15 , wherein said second therapeutic agent is an agent useful in the treatment or prevention of a disease or condition selected from depression, anxiety, bipolar disorder, and sleep disorder. 
   
   
       17 . A method of treating a subject suffering from, or susceptible to, a disease selected from depression, anxiety, bipolar disorder, and sleep disorders comprising the step of administering to the subject in need thereof a composition of  claim 14 . 
   
   
       18 . The method of  claim 17 , wherein the disease or condition is selected from depression, and bipolar disorder. 
   
   
       19 . The method of  claim 18 , comprising the additional step of co-administering to the subject in need thereof a second therapeutic agent.