Method of treating hair loss using diphenylether derivatives

Abstract

The present disclosure describes methods for treating hair loss in mammals, including arresting and/or reversing hair loss and promoting hair growth. The methods comprise administering a cardiac-sparing compound having a structure of formula (I) as described herein and a pharmaceutically-acceptable carrier.

What is claimed is:  
     
         1 . A method of treating hair loss comprising administering a composition comprising a cardiac-sparing compound characterized by the structure:  
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts, hydrates, and biohydrolyzable amides, esters, and imides thereof, wherein: 
 R is selected from the group consisting of hydrogen, hydroxy, esterified hydroxy, and etherified hydroxy;  
 R 1 , R 2 , and R 4  are each, independently, selected from the group consisting of hydrogen, halogen, trifluoromethyl and lower alkyl;  
 R 3  is selected from the group consisting of halogen, trifluoromethyl, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, and:  
                     
 R 8  is selected from the group consisting of hydrogen, lower alkyl, aryl, cycloalkyl, aryl-lower alkyl, and cycloalkyl-lower alkyl;  
 R 9  is selected from the group consisting of hydroxy and acyloxy;  
 R 10  is selected from the group consisting of hydrogen and lower alkyl; with the proviso that R 9  and R 10  collectively optionally represent oxo;  
 W is selected from the group consisting of —O— and —S—;  
 X is selected from the group consisting of —NR 7 , S, and O;  
 R 5  is selected from the group consisting of hydrogen, lower alkyl, and aryl-lower alkyl and R 6  is hydrogen; with the proviso that when X is —NR 7 , R 5  and R 6  together are optionally oxo;  
 R 7  is selected from the group consisting of hydrogen and lower alkyl; and  
 Z is selected from the group consisting of carboxyl and carboxyl derivatized as a pharmaceutically acceptable ester or amide.  
 
     
     
         2 . A method according to  claim 1  wherein X is —NR 7  and R 5  and R 6  together are oxo.  
     
     
         3 . A method according to any of claims  1  and  2  wherein: 
 R substitutes on the 4′ position;  
 R 1  substitutes on the 3 position;  
 R 2  substitutes on the 5 position;  
 R 3  substitutes on the 3′ position; and  
 R 4  substitutes on the 5′ position.  
 
     
     
         4 . A method according any of claims  1  and  2  wherein: 
 W is —O—;  
 R is selected from the group consisting of hydroxy, esterified hydroxy, and etherified hydroxy;  
 R 4  is hydrogen;  
 R 3  is selected from the group consisting of lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl and  
                     
  and  
 Z is selected from the group consisting of carboxyl and carboxyl derivatized as a pharmaceutically acceptable ester.  
 
     
     
         5 . A method according to  claim 4  wherein the compound is characterized by the structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are each, independently, selected from the group consisting of hydrogen, halogen, trifluoromethyl, and C 1 -C 3  alkyl.  
     
     
         6 . A method according  claim 5  wherein R 7  is selected from the group consisting of hydrogen and C 1 -C 3  alkyl.  
     
     
         7 . A method according to any of claims  5  and  6  wherein R is hydroxy.  
     
     
         8 . A method according to any of claims  5 ,  6 , and  7  wherein R 3  is selected from the group consisting of isopropyl, benzyl, benzyl substituted with halogen, and trifluoromethyl.  
     
     
         9 . A method according to any of claims  5 ,  6 ,  7 , and  8  wherein Z is carboxyl.  
     
     
         10 . A method according to any of the preceding claims wherein the administration is topical.