Pharmaceutical formulations comprising neurotrophin mimetics

Abstract

Methods and compounds for treating neurodegenerative and other disorders. Included is the administering to a subject in need thereof an effective amount of a compound having binding specificity for a p75 NTR receptor molecule. Enhanced survival of neural and other cells has been observed.

1 - 51 . (canceled) 
     
     
         52 . A pharmaceutical formulation comprising a unit dose of an active ingredient and a pharmaceutical grade carrier, wherein said active ingredient comprises a compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         n is an integer from 0 to 8; 
         L 1  is a linking group selected from the group consisting of alkylene, substituted alkylene, cycloalkyl, substituted cycloalkyl, cycloalkylene, substituted cycloalkylene, aryl, substituted aryl, alkenylene, and substituted alkenylene; 
         R 1  and R 2  are each independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, halo, cyano, nitro, mercapto, hydroxyl, alkoxyl, aryl, aryloxyl, substituted aryl, and aralkyloxyl; 
         A 1 , A 2 , A 3 , and A 4  are each independently selected from the group consisting of N and CH; 
         B 1 , B 2  and B 3  are each independently selected from the group consisting of 0, S, and NR 4 , wherein R 4  is selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, aryl, and substituted aryl; and 
         D 1  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
       
       wherein:
 each R 5 , R 6 , R 8 , R 9 , and R 10  is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, aralkyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; 
 each R 7  is independently selected from the group consisting of H, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, acyloxyl, and alkoxyl; or 
 R 7  and R 5  or R 7  and R 9  together represent a C 2  to C 10  alkyl, C 2  to C 10  hydroxyalkyl, or C 2  to C 10  alkene; 
 or a pharmaceutically acceptable salt, solvate, or ester thereof. 
 
     
     
         53 . The pharmaceutical formulation of  claim 52 , wherein L 1  is —(CH 2 ) m — and m is an integer from 1 to 8. 
     
     
         54 . The pharmaceutical formulation of  claim 52 , wherein said compound of Formula (I) has the structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 m is an integer from 1 to 8; 
 R 1  and R 2  are each independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, aryl, aryloxyl, substituted aryl, and aralkyloxyl; and 
 R 5  and R 6  are each independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; 
 
       or a pharmaceutically acceptable salt, solvate, or ester thereof. 
     
     
         55 . The pharmaceutical formulation of  claim 54 , wherein said compound of Formula (I) has the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or ester thereof. 
     
     
         56 . The pharmaceutical formulation of  claim 52 , which is a liquid solution, suspension, emulsion, tablet, pill, or capsule. 
     
     
         57 . The pharmaceutical formulation of  claim 56 , formulated for administration to a human.