Substituted pyran derivatives

Abstract

Certain 3,6-disubstituted and 2, 4, 5-trisubstituted pyran derivatives that exhibit potent activity on monoamine transport systems are provided. The 3, 6 and 2, 4, 5 pyrans are useful in probing the effects of their binding to monoamine transporter systems and the corresponding relationships to various afflictions affecting the CNS, or as a treatment for various CNS-related disorders in which the monoamine transport and related systems are implicated.

What is claimed is: 
     
         1 . A compound having formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable derivative or salt thereof; 
         wherein; 
         p is 0 to 5; 
         R is 
       
       
         
           
           
               
               
           
         
         W is H, OH, or NHR o ; 
         R 0  is H or C 1-18  alkyl; 
         R 1  is C 1-4  alkyl, C 2-6  alkenyl, C 2-6  optionally halogenated alkynyl, C 2-6  hydroxyalkynyl, halo, —CN, —COOR 2 , C 5-10  cycloalkyl, C 2-18  alkenyl, —OH, —NO 2 , —NHR 2 , or —OR 2 ; 
         R 2  is C 1-8  alkyl, C 5-6  cycloalkyl, or C 2-8  alkenyl; 
         R 3  is F, Cl, Br, OR 4 , NO 2 , NHR 4 , NH(CO)R 4 , N(CO)OR 4 , SO 2 NH 2 , or N(R 4 ) 2 ; 
         the dashed line is an optional bond; 
         T is CH or N; 
         r is 0 to 5; 
         X, Y, and Z are each independently CR 4 , CR 4   2 , C—NHR 4 , C═O, S, N, or NR 4 ; and 
         R 4  is H or C 1-8  alkyl. 
       
     
     
         2 . The compound of  claim 1  wherein R is: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1  wherein R is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1  having a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 1  having a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . A compound having formula 4: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable derivative or salt thereof; 
         where R is 
       
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 6  wherein R is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound having formula 6: 
       
         
           
           
               
               
           
         
         wherein R is: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 8  wherein R is:
 wherein R is: 
 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 8  wherein R is: